ALDOSE REDUCTASE INHIBITORY POTENTIAL OF PATULETIN: A COMPREHENSIVE IN VITRO ANALYSIS INTEGRATING ADMET, MOLECULAR DOCKING, AND MD STUDIES FOR PREDICTED UPSTREAM ANTICANCER PATHWAY
Main Article Content
Keywords
Patuletin, aldose reductase, molecular docking, ADMET, anticancer
Abstract
Patuletin is a rare flavonoid with various anticancer, anti-inflammatory, antiviral, antinociceptive, and skin-lightening effects. It inhibits fatty acid synthase, lipoxygenase, TNF alpha, and targets the JAK-STAT system, reducing ROS through p38 and NF-κB. Patuletin triggers PARP and caspase 3 activation, which are linked to the enzyme aldose reductase.
This study evaluates the predicted inhibitory pathway of patuletin as an aldose reductase inhibitor using SWISSADME, PKSCM web tools, Stoptox, protox 3.0, Swiss target prediction, passonline, similarity ensemble approach (SEA), IMOD platform, Swiss Autodock Vina, Pyrx, and Discovery Studio for molecular docking.
Patuletin has a logP (lipophilicity) of 2.0 and TPSA of 140.9Ų, which may limit bioavailability and cause drug interactions. It is non-toxic for acute inhalation and oral toxicity but exhibits toxic behavior for acute dermal toxicity. Swiss Target Prediction predicts its most probable protein targets, including 27.6% of lyases, 20% of enzymes, 13.3% of kinases, and 6.7% of proteases, oxidoreductases, and family A G couple protein receptors. The Similarity Ensemble Approach (SEA) evaluates ligand similarity using the Tanimoto coefficient (Tc). Patuletin showed the highest TC with Aldo-keto reductase family 1 member B1 (AKR1B1) 0.86 for rat and 0.7 for human. The study investigates the molecular docking of the aldose reductase protein with the ligand nicotinamide adenine dinucleotide phosphate (NADP) and the standard drug epalrestat. The results show that patuletin is more effective than regular epalrestat due to its inhibitory properties and binding affinity. The molecular docking tests for patuletin against 1ADS and against epalrestat showed similar binding energy. All three ligands showed the same site interactions i.e. Trp20, Tyr209 Tyr48, ASN160 and Cys298 and a Swissdock was used for molecular revalidation, confirming the same results.
It is concluded that patuletin may target aldose reductase AKR1B1 and have an inhibitory effect; however, additional experimental testing is necessary to confirm this possibility.
References
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2. Rauf A, Khan MU, Akram Z, et al. Lipoxygenase inhibitory potential of secondary metabolites isolated from Pistacia integerrima: a comprehensive in vitro analysis integrating molecular docking, ADMET and DFT studies. Tradit Med Res 2025;10:52–57 doi: https://doi.org/10.53388/TMR20241203001.
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4. Siddiqui R, Khatoon B, Kawish M, et al. The potential of nanocomposites (patuletin-conjugated with gallic acid-coated zinc oxide) against free-living amoebae pathogens. International Microbiology 2025;28(5):929-39 doi: 10.1007/s10123-024-00584-w.
5. Ateeq M, Shah MR, ul Ain N, et al. Green synthesis and molecular recognition ability of patuletin coated gold nanoparticles. Biosensors and Bioelectronics 2015;63:499-505.
6. Patel DK, Singh GK, Husain GM, Prasad SK. Ethnomedicinal importance of patuletin in medicine: pharmacological activities and analytical aspects. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 2024;24(5):519-30.
7. Zhu W, Lv C, Wang J, Gao Q, Zhu H, Wen H. Patuletin induces apoptosis of human breast cancer SK‑BR‑3 cell line via inhibiting fatty acid synthase gene expression and activity. Oncology Letters 2017;14(6):7449-54.
8. Alvarado-Sansininea JJ, Sánchez-Sánchez L, López-Muñoz H, et al. Quercetagetin and patuletin: Antiproliferative, necrotic and apoptotic activity in tumor cell lines. Molecules 2018;23(10):2579.
9. Kang Y-L, Kim J, Kwak S-B, Kim Y-S, Huh J, Park J-W. The polyol pathway and nuclear ketohexokinase A signaling drive hyperglycemia-induced metastasis of gastric cancer. Experimental & Molecular Medicine 2024;56:220-34 doi: 10.1038/s12276-023-01153-3.
10. Han B, Wang L, Wei M, et al. Fructose fuels tumor growth through the polyol pathway and GLUT 8 transporter. bioRxiv 2020 doi: 10.1101/2020.06.04.132902.
11. Tammali R, Srivastava SK, Ramana KV. Targeting aldose reductase for the treatment of cancer. Curr Cancer Drug Targets 2011;11(5):560-71 doi: 10.2174/156800911795655958.
12. Zognjani B, Nixha AR, Duran HE, et al. N-substituted phthalimide–carboxylic acid hybrids as dual-targeted aldose reductase inhibitors: Synthesis, mechanistic insights, and cancer-relevant profiling. Bioorganic Chemistry 2025;163:108788 doi: https://doi.org/10.1016/j.bioorg.2025.108788.
13. Penning TM. Aldo-Keto Reductase Regulation by the Nrf2 System: Implications for Stress Response, Chemotherapy Drug Resistance, and Carcinogenesis. Chem Res Toxicol 2017;30(1):162-76 doi: 10.1021/acs.chemrestox.6b00319 [published Online First: 20161116].
14. Penning TM, Jonnalagadda S, Trippier PC, Rižner TL. Aldo-Keto Reductases and Cancer Drug Resistance. Pharmacol Rev 2021;73(3):1150-71 doi: 10.1124/pharmrev.120.000122.
15. Hu Q, Bian Q, Rong D, et al. JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens. Frontiers in Bioengineering and Biotechnology 2023;11 doi: 10.3389/fbioe.2023.1110765.
16. Syamprasad N, Rajdev B, Jain S, et al. Pivotal role of AKR1B1 in pathogenesis of colitis associated colorectal carcinogenesis. International immunopharmacology 2023;119:110145 doi: 10.1016/j.intimp.2023.110145.
17. Balestri F, Moschini R, Mura U, Cappiello M, Del Corso A. In Search of Differential Inhibitors of Aldose Reductase. Biomolecules 2022;12(4) doi: 10.3390/biom12040485 [published Online First: 20220322].
18. Khalid M, Petroianu G, Adem A. Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives. Biomolecules 2022;12 doi: 10.3390/biom12040542.
19. Zanoni M, Bravaccini S, Fabbri F, Arienti C. Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance. Frontiers in Medicine 2022;9 doi: 10.3389/fmed.2022.795762.
20. Lyon RC, Li D, McGarvie G, Ellis EM. Aldo-keto reductases mediate constitutive and inducible protection against aldehyde toxicity in human neuroblastoma SH-SY5Y cells. Neurochem Int 2013;62(1):113-21 doi: 10.1016/j.neuint.2012.10.007 [published Online First: 20121022].
21. Cho SJ, Kang KA, Piao MJ, et al. 7,8-Dihydroxyflavone Protects High Glucose-Damaged Neuronal Cells against Oxidative Stress. Biomol Ther (Seoul) 2019;27(1):85-91 doi: 10.4062/biomolther.2018.202.
22. Srivastava SK, Yadav UC, Reddy AB, et al. Aldose reductase inhibition suppresses oxidative stress-induced inflammatory disorders. Chem Biol Interact 2011;191(1-3):330-8 doi: 10.1016/j.cbi.2011.02.023 [published Online First: 20110224].
23. Shoeb M, Yadav UC, Srivastava SK, Ramana KV. Inhibition of aldose reductase prevents endotoxin-induced inflammation by regulating the arachidonic acid pathway in murine macrophages. Free Radic Biol Med 2011;51(9):1686-96 doi: 10.1016/j.freeradbiomed.2011.07.024 [published Online First: 20110805].
24. Rauf A, Khan M, Akram Z, et al. Lipoxygenase inhibitory potential of secondary metabolites isolated from Pistacia integerrima: a comprehensive in vitro analysis integrating molecular docking, ADMET and DFT studies. Tradit Med. Res. 2025;10:52.
25. Wu T-G, Ke Y, Tang H, Liao C, Li J, Wang L. Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma. Molecular Therapy Oncolytics 2021;23:420-31 doi: 10.1016/j.omto.2021.06.005.
26. Zhao JX, Yuan YW, Cai CF, et al. Aldose reductase interacts with AKT1 to augment hepatic AKT/mTOR signaling and promote hepatocarcinogenesis. Oncotarget 2017;8(40):66987-7000 doi: 10.18632/oncotarget.17791 [published Online First: 20170510].
27. Bailly C. Moving toward a new horizon for the aldose reductase inhibitor epalrestat to treat drug-resistant cancer. European Journal of Pharmacology 2022;931:175191 doi: https://doi.org/10.1016/j.ejphar.2022.175191.
28. Metwaly AM, Saleh MM, Alsfouk BA, et al. Anti-virulence potential of patuletin, a natural flavone, against Staphylococcus aureus: In vitro and In silico investigations. Heliyon 2024;10(2).
29. Metwaly A, Saleh MM, Alsfouk A, et al. In silico and in vitro evaluation of the anti-virulence potential of patuletin, a natural methoxy flavone, against Pseudomonas aeruginosa. PeerJ 2024;12:e16826.
30. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports 2017;7(1):42717 doi: 10.1038/srep42717.
31. Pires DEV, Blundell TL, Ascher DB. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. Journal of Medicinal Chemistry 2015;58(9):4066-72 doi: 10.1021/acs.jmedchem.5b00104.
32. Banerjee P, Ulker O, Ozkan I, Ulker OC. The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox- 3.0. Toxicology Mechanisms and Methods 2025;35(1):32-42 doi: 10.1080/15376516.2024.2382815.
33. Borba Joyce VB, Alves Vinicius M, Braga Rodolpho C, et al. STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity. Environmental Health Perspectives;130(2):027012 doi: 10.1289/EHP9341.
34. Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic acids research 2014;42 doi: 10.1093/nar/gku293.
35. DHONGADE S. APPLICATION OF PASS AS AN EFFECTIVE DRUG DESIGNING TOOL. Reviews of Literature• Volume 2013;1(1).
36. Filimonov D, Lagunin A, Poroikov V. Prediction of activity spectra for substances using new local integrative descriptors. QSAR and Molecular Modelling in Rational Design of Bioactive Molecules. Esin Aki Sener, Ismail Yalcin Eds., Ankara (Turkey) 2005:98-99.
37. Lagunin A, Stepanchikova A, Filimonov D, Poroikov V. PASS: Prediction of activity spectra for biologically active substances. Bioinformatics (Oxford, England) 2000;16:747-8 doi: 10.1093/bioinformatics/16.8.747.
38. Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotechnol 2007;25(2):197-206 doi: 10.1038/nbt1284.
39. Abdulhakeem Mansour Alhasbary A, Hashimah Ahamed Hassain Malim N, Zuraidah Mohamad Zobir S. Exploring natural products potential: A similarity-based target prediction tool for natural products. Computers in Biology and Medicine 2025;184:109351 doi: https://doi.org/10.1016/j.compbiomed.2024.109351.
40. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA. An Unlikely Sugar Substrate Site in the 1.65 Å Structure of the Human Aldose Reductase Holoenzyme Implicated in Diabetic Complications. Science 1992;257(5066):81-84 doi: doi:10.1126/science.1621098.
41. Suriyeni D, Mukarromah Z, Ridho MR, Ridho MA. Eksplorasi Molecular Docking Senyawa Flavonoid Orthosiphon Stamineus B. Reseptor Enzim Siklooksigenase (COX) Sebagai Antiinflamasi. Blantika: Multidisciplinary Journal 2024;2(8).
42. Ounthaisong U, Tangyuenyongwatana P. Cross-docking study of flavonoids against tyrosinase enzymes using PyRx 0.8 virtual screening tool. TJPS 2017;41(2017).
43. Rajab MS. In silico larvicidal activity study of six limonoids against mosquito larvae (Aedes aegypti L.) ecdysone receptor protein. Sciences of Phytochemistry 2024;3(1):20-26.
44. Zhao Y, Hou Y, Ren J, et al. Phenotypic characteristics of taurodontism and a novel WNT10A variant in non-syndromic oligodontia family. Archives of Oral Biology 2023;154:105759.
45. Ali Kharl H, Nadeem H, Khan A, et al. Synthesis, Molecular Docking, and Investigation of Enzyme Inhibition Activities of Benzimidazole-Pyrazole Hybrids. J Vis Exp 2025;1.
46. Wu F, Zhou Y, Li L, et al. Computational Approaches in Preclinical Studies on Drug Discovery and Development. Frontiers in Chemistry 2020;Volume 8 - 2020 doi: 10.3389/fchem.2020.00726.
47. López-Blanco JR, Aliaga JI, Quintana-Ortí ES, Chacón P. iMODS: internal coordinates normal mode analysis server. Nucleic Acids Res 2014;42(Web Server issue):W271-6 doi: 10.1093/nar/gku339 [published Online First: 20140425].
1. Schnall S, Benton J, Harvey S. With a Clean Conscience:Cleanliness Reduces the Severity of Moral Judgments. Psychological Science 2008;19(12):1219-22 doi: 10.1111/j.1467-9280.2008.02227.x.
2. Rauf A, Khan MU, Akram Z, et al. Lipoxygenase inhibitory potential of secondary metabolites isolated from Pistacia integerrima: a comprehensive in vitro analysis integrating molecular docking, ADMET and DFT studies. Tradit Med Res 2025;10:52–57 doi: https://doi.org/10.53388/TMR20241203001.
3. Nijveldt RJ, van Nood E, van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAM. Flavonoids: a review of probable mechanisms of action and potential applications123. The American Journal of Clinical Nutrition 2001;74(4):418-25 doi: https://doi.org/10.1093/ajcn/74.4.418.
4. Siddiqui R, Khatoon B, Kawish M, et al. The potential of nanocomposites (patuletin-conjugated with gallic acid-coated zinc oxide) against free-living amoebae pathogens. International Microbiology 2025;28(5):929-39 doi: 10.1007/s10123-024-00584-w.
5. Ateeq M, Shah MR, ul Ain N, et al. Green synthesis and molecular recognition ability of patuletin coated gold nanoparticles. Biosensors and Bioelectronics 2015;63:499-505.
6. Patel DK, Singh GK, Husain GM, Prasad SK. Ethnomedicinal importance of patuletin in medicine: pharmacological activities and analytical aspects. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 2024;24(5):519-30.
7. Zhu W, Lv C, Wang J, Gao Q, Zhu H, Wen H. Patuletin induces apoptosis of human breast cancer SK‑BR‑3 cell line via inhibiting fatty acid synthase gene expression and activity. Oncology Letters 2017;14(6):7449-54.
8. Alvarado-Sansininea JJ, Sánchez-Sánchez L, López-Muñoz H, et al. Quercetagetin and patuletin: Antiproliferative, necrotic and apoptotic activity in tumor cell lines. Molecules 2018;23(10):2579.
9. Kang Y-L, Kim J, Kwak S-B, Kim Y-S, Huh J, Park J-W. The polyol pathway and nuclear ketohexokinase A signaling drive hyperglycemia-induced metastasis of gastric cancer. Experimental & Molecular Medicine 2024;56:220-34 doi: 10.1038/s12276-023-01153-3.
10. Han B, Wang L, Wei M, et al. Fructose fuels tumor growth through the polyol pathway and GLUT 8 transporter. bioRxiv 2020 doi: 10.1101/2020.06.04.132902.
11. Tammali R, Srivastava SK, Ramana KV. Targeting aldose reductase for the treatment of cancer. Curr Cancer Drug Targets 2011;11(5):560-71 doi: 10.2174/156800911795655958.
12. Zognjani B, Nixha AR, Duran HE, et al. N-substituted phthalimide–carboxylic acid hybrids as dual-targeted aldose reductase inhibitors: Synthesis, mechanistic insights, and cancer-relevant profiling. Bioorganic Chemistry 2025;163:108788 doi: https://doi.org/10.1016/j.bioorg.2025.108788.
13. Penning TM. Aldo-Keto Reductase Regulation by the Nrf2 System: Implications for Stress Response, Chemotherapy Drug Resistance, and Carcinogenesis. Chem Res Toxicol 2017;30(1):162-76 doi: 10.1021/acs.chemrestox.6b00319 [published Online First: 20161116].
14. Penning TM, Jonnalagadda S, Trippier PC, Rižner TL. Aldo-Keto Reductases and Cancer Drug Resistance. Pharmacol Rev 2021;73(3):1150-71 doi: 10.1124/pharmrev.120.000122.
15. Hu Q, Bian Q, Rong D, et al. JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens. Frontiers in Bioengineering and Biotechnology 2023;11 doi: 10.3389/fbioe.2023.1110765.
16. Syamprasad N, Rajdev B, Jain S, et al. Pivotal role of AKR1B1 in pathogenesis of colitis associated colorectal carcinogenesis. International immunopharmacology 2023;119:110145 doi: 10.1016/j.intimp.2023.110145.
17. Balestri F, Moschini R, Mura U, Cappiello M, Del Corso A. In Search of Differential Inhibitors of Aldose Reductase. Biomolecules 2022;12(4) doi: 10.3390/biom12040485 [published Online First: 20220322].
18. Khalid M, Petroianu G, Adem A. Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives. Biomolecules 2022;12 doi: 10.3390/biom12040542.
19. Zanoni M, Bravaccini S, Fabbri F, Arienti C. Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance. Frontiers in Medicine 2022;9 doi: 10.3389/fmed.2022.795762.
20. Lyon RC, Li D, McGarvie G, Ellis EM. Aldo-keto reductases mediate constitutive and inducible protection against aldehyde toxicity in human neuroblastoma SH-SY5Y cells. Neurochem Int 2013;62(1):113-21 doi: 10.1016/j.neuint.2012.10.007 [published Online First: 20121022].
21. Cho SJ, Kang KA, Piao MJ, et al. 7,8-Dihydroxyflavone Protects High Glucose-Damaged Neuronal Cells against Oxidative Stress. Biomol Ther (Seoul) 2019;27(1):85-91 doi: 10.4062/biomolther.2018.202.
22. Srivastava SK, Yadav UC, Reddy AB, et al. Aldose reductase inhibition suppresses oxidative stress-induced inflammatory disorders. Chem Biol Interact 2011;191(1-3):330-8 doi: 10.1016/j.cbi.2011.02.023 [published Online First: 20110224].
23. Shoeb M, Yadav UC, Srivastava SK, Ramana KV. Inhibition of aldose reductase prevents endotoxin-induced inflammation by regulating the arachidonic acid pathway in murine macrophages. Free Radic Biol Med 2011;51(9):1686-96 doi: 10.1016/j.freeradbiomed.2011.07.024 [published Online First: 20110805].
24. Rauf A, Khan M, Akram Z, et al. Lipoxygenase inhibitory potential of secondary metabolites isolated from Pistacia integerrima: a comprehensive in vitro analysis integrating molecular docking, ADMET and DFT studies. Tradit Med. Res. 2025;10:52.
25. Wu T-G, Ke Y, Tang H, Liao C, Li J, Wang L. Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma. Molecular Therapy Oncolytics 2021;23:420-31 doi: 10.1016/j.omto.2021.06.005.
26. Zhao JX, Yuan YW, Cai CF, et al. Aldose reductase interacts with AKT1 to augment hepatic AKT/mTOR signaling and promote hepatocarcinogenesis. Oncotarget 2017;8(40):66987-7000 doi: 10.18632/oncotarget.17791 [published Online First: 20170510].
27. Bailly C. Moving toward a new horizon for the aldose reductase inhibitor epalrestat to treat drug-resistant cancer. European Journal of Pharmacology 2022;931:175191 doi: https://doi.org/10.1016/j.ejphar.2022.175191.
28. Metwaly AM, Saleh MM, Alsfouk BA, et al. Anti-virulence potential of patuletin, a natural flavone, against Staphylococcus aureus: In vitro and In silico investigations. Heliyon 2024;10(2).
29. Metwaly A, Saleh MM, Alsfouk A, et al. In silico and in vitro evaluation of the anti-virulence potential of patuletin, a natural methoxy flavone, against Pseudomonas aeruginosa. PeerJ 2024;12:e16826.
30. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports 2017;7(1):42717 doi: 10.1038/srep42717.
31. Pires DEV, Blundell TL, Ascher DB. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. Journal of Medicinal Chemistry 2015;58(9):4066-72 doi: 10.1021/acs.jmedchem.5b00104.
32. Banerjee P, Ulker O, Ozkan I, Ulker OC. The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox- 3.0. Toxicology Mechanisms and Methods 2025;35(1):32-42 doi: 10.1080/15376516.2024.2382815.
33. Borba Joyce VB, Alves Vinicius M, Braga Rodolpho C, et al. STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity. Environmental Health Perspectives;130(2):027012 doi: 10.1289/EHP9341.
34. Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic acids research 2014;42 doi: 10.1093/nar/gku293.
35. DHONGADE S. APPLICATION OF PASS AS AN EFFECTIVE DRUG DESIGNING TOOL. Reviews of Literature• Volume 2013;1(1).
36. Filimonov D, Lagunin A, Poroikov V. Prediction of activity spectra for substances using new local integrative descriptors. QSAR and Molecular Modelling in Rational Design of Bioactive Molecules. Esin Aki Sener, Ismail Yalcin Eds., Ankara (Turkey) 2005:98-99.
37. Lagunin A, Stepanchikova A, Filimonov D, Poroikov V. PASS: Prediction of activity spectra for biologically active substances. Bioinformatics (Oxford, England) 2000;16:747-8 doi: 10.1093/bioinformatics/16.8.747.
38. Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotechnol 2007;25(2):197-206 doi: 10.1038/nbt1284.
39. Abdulhakeem Mansour Alhasbary A, Hashimah Ahamed Hassain Malim N, Zuraidah Mohamad Zobir S. Exploring natural products potential: A similarity-based target prediction tool for natural products. Computers in Biology and Medicine 2025;184:109351 doi: https://doi.org/10.1016/j.compbiomed.2024.109351.
40. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA. An Unlikely Sugar Substrate Site in the 1.65 Å Structure of the Human Aldose Reductase Holoenzyme Implicated in Diabetic Complications. Science 1992;257(5066):81-84 doi: doi:10.1126/science.1621098.
41. Suriyeni D, Mukarromah Z, Ridho MR, Ridho MA. Eksplorasi Molecular Docking Senyawa Flavonoid Orthosiphon Stamineus B. Reseptor Enzim Siklooksigenase (COX) Sebagai Antiinflamasi. Blantika: Multidisciplinary Journal 2024;2(8).
42. Ounthaisong U, Tangyuenyongwatana P. Cross-docking study of flavonoids against tyrosinase enzymes using PyRx 0.8 virtual screening tool. TJPS 2017;41(2017).
43. Rajab MS. In silico larvicidal activity study of six limonoids against mosquito larvae (Aedes aegypti L.) ecdysone receptor protein. Sciences of Phytochemistry 2024;3(1):20-26.
44. Zhao Y, Hou Y, Ren J, et al. Phenotypic characteristics of taurodontism and a novel WNT10A variant in non-syndromic oligodontia family. Archives of Oral Biology 2023;154:105759.
45. Ali Kharl H, Nadeem H, Khan A, et al. Synthesis, Molecular Docking, and Investigation of Enzyme Inhibition Activities of Benzimidazole-Pyrazole Hybrids. J Vis Exp 2025;1.
46. Wu F, Zhou Y, Li L, et al. Computational Approaches in Preclinical Studies on Drug Discovery and Development. Frontiers in Chemistry 2020;Volume 8 - 2020 doi: 10.3389/fchem.2020.00726.
47. López-Blanco JR, Aliaga JI, Quintana-Ortí ES, Chacón P. iMODS: internal coordinates normal mode analysis server. Nucleic Acids Res 2014;42(Web Server issue):W271-6 doi: 10.1093/nar/gku339 [published Online First: 20140425].
2. Rauf A, Khan MU, Akram Z, et al. Lipoxygenase inhibitory potential of secondary metabolites isolated from Pistacia integerrima: a comprehensive in vitro analysis integrating molecular docking, ADMET and DFT studies. Tradit Med Res 2025;10:52–57 doi: https://doi.org/10.53388/TMR20241203001.
3. Nijveldt RJ, van Nood E, van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAM. Flavonoids: a review of probable mechanisms of action and potential applications123. The American Journal of Clinical Nutrition 2001;74(4):418-25 doi: https://doi.org/10.1093/ajcn/74.4.418.
4. Siddiqui R, Khatoon B, Kawish M, et al. The potential of nanocomposites (patuletin-conjugated with gallic acid-coated zinc oxide) against free-living amoebae pathogens. International Microbiology 2025;28(5):929-39 doi: 10.1007/s10123-024-00584-w.
5. Ateeq M, Shah MR, ul Ain N, et al. Green synthesis and molecular recognition ability of patuletin coated gold nanoparticles. Biosensors and Bioelectronics 2015;63:499-505.
6. Patel DK, Singh GK, Husain GM, Prasad SK. Ethnomedicinal importance of patuletin in medicine: pharmacological activities and analytical aspects. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders) 2024;24(5):519-30.
7. Zhu W, Lv C, Wang J, Gao Q, Zhu H, Wen H. Patuletin induces apoptosis of human breast cancer SK‑BR‑3 cell line via inhibiting fatty acid synthase gene expression and activity. Oncology Letters 2017;14(6):7449-54.
8. Alvarado-Sansininea JJ, Sánchez-Sánchez L, López-Muñoz H, et al. Quercetagetin and patuletin: Antiproliferative, necrotic and apoptotic activity in tumor cell lines. Molecules 2018;23(10):2579.
9. Kang Y-L, Kim J, Kwak S-B, Kim Y-S, Huh J, Park J-W. The polyol pathway and nuclear ketohexokinase A signaling drive hyperglycemia-induced metastasis of gastric cancer. Experimental & Molecular Medicine 2024;56:220-34 doi: 10.1038/s12276-023-01153-3.
10. Han B, Wang L, Wei M, et al. Fructose fuels tumor growth through the polyol pathway and GLUT 8 transporter. bioRxiv 2020 doi: 10.1101/2020.06.04.132902.
11. Tammali R, Srivastava SK, Ramana KV. Targeting aldose reductase for the treatment of cancer. Curr Cancer Drug Targets 2011;11(5):560-71 doi: 10.2174/156800911795655958.
12. Zognjani B, Nixha AR, Duran HE, et al. N-substituted phthalimide–carboxylic acid hybrids as dual-targeted aldose reductase inhibitors: Synthesis, mechanistic insights, and cancer-relevant profiling. Bioorganic Chemistry 2025;163:108788 doi: https://doi.org/10.1016/j.bioorg.2025.108788.
13. Penning TM. Aldo-Keto Reductase Regulation by the Nrf2 System: Implications for Stress Response, Chemotherapy Drug Resistance, and Carcinogenesis. Chem Res Toxicol 2017;30(1):162-76 doi: 10.1021/acs.chemrestox.6b00319 [published Online First: 20161116].
14. Penning TM, Jonnalagadda S, Trippier PC, Rižner TL. Aldo-Keto Reductases and Cancer Drug Resistance. Pharmacol Rev 2021;73(3):1150-71 doi: 10.1124/pharmrev.120.000122.
15. Hu Q, Bian Q, Rong D, et al. JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens. Frontiers in Bioengineering and Biotechnology 2023;11 doi: 10.3389/fbioe.2023.1110765.
16. Syamprasad N, Rajdev B, Jain S, et al. Pivotal role of AKR1B1 in pathogenesis of colitis associated colorectal carcinogenesis. International immunopharmacology 2023;119:110145 doi: 10.1016/j.intimp.2023.110145.
17. Balestri F, Moschini R, Mura U, Cappiello M, Del Corso A. In Search of Differential Inhibitors of Aldose Reductase. Biomolecules 2022;12(4) doi: 10.3390/biom12040485 [published Online First: 20220322].
18. Khalid M, Petroianu G, Adem A. Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives. Biomolecules 2022;12 doi: 10.3390/biom12040542.
19. Zanoni M, Bravaccini S, Fabbri F, Arienti C. Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance. Frontiers in Medicine 2022;9 doi: 10.3389/fmed.2022.795762.
20. Lyon RC, Li D, McGarvie G, Ellis EM. Aldo-keto reductases mediate constitutive and inducible protection against aldehyde toxicity in human neuroblastoma SH-SY5Y cells. Neurochem Int 2013;62(1):113-21 doi: 10.1016/j.neuint.2012.10.007 [published Online First: 20121022].
21. Cho SJ, Kang KA, Piao MJ, et al. 7,8-Dihydroxyflavone Protects High Glucose-Damaged Neuronal Cells against Oxidative Stress. Biomol Ther (Seoul) 2019;27(1):85-91 doi: 10.4062/biomolther.2018.202.
22. Srivastava SK, Yadav UC, Reddy AB, et al. Aldose reductase inhibition suppresses oxidative stress-induced inflammatory disorders. Chem Biol Interact 2011;191(1-3):330-8 doi: 10.1016/j.cbi.2011.02.023 [published Online First: 20110224].
23. Shoeb M, Yadav UC, Srivastava SK, Ramana KV. Inhibition of aldose reductase prevents endotoxin-induced inflammation by regulating the arachidonic acid pathway in murine macrophages. Free Radic Biol Med 2011;51(9):1686-96 doi: 10.1016/j.freeradbiomed.2011.07.024 [published Online First: 20110805].
24. Rauf A, Khan M, Akram Z, et al. Lipoxygenase inhibitory potential of secondary metabolites isolated from Pistacia integerrima: a comprehensive in vitro analysis integrating molecular docking, ADMET and DFT studies. Tradit Med. Res. 2025;10:52.
25. Wu T-G, Ke Y, Tang H, Liao C, Li J, Wang L. Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma. Molecular Therapy Oncolytics 2021;23:420-31 doi: 10.1016/j.omto.2021.06.005.
26. Zhao JX, Yuan YW, Cai CF, et al. Aldose reductase interacts with AKT1 to augment hepatic AKT/mTOR signaling and promote hepatocarcinogenesis. Oncotarget 2017;8(40):66987-7000 doi: 10.18632/oncotarget.17791 [published Online First: 20170510].
27. Bailly C. Moving toward a new horizon for the aldose reductase inhibitor epalrestat to treat drug-resistant cancer. European Journal of Pharmacology 2022;931:175191 doi: https://doi.org/10.1016/j.ejphar.2022.175191.
28. Metwaly AM, Saleh MM, Alsfouk BA, et al. Anti-virulence potential of patuletin, a natural flavone, against Staphylococcus aureus: In vitro and In silico investigations. Heliyon 2024;10(2).
29. Metwaly A, Saleh MM, Alsfouk A, et al. In silico and in vitro evaluation of the anti-virulence potential of patuletin, a natural methoxy flavone, against Pseudomonas aeruginosa. PeerJ 2024;12:e16826.
30. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports 2017;7(1):42717 doi: 10.1038/srep42717.
31. Pires DEV, Blundell TL, Ascher DB. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. Journal of Medicinal Chemistry 2015;58(9):4066-72 doi: 10.1021/acs.jmedchem.5b00104.
32. Banerjee P, Ulker O, Ozkan I, Ulker OC. The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox- 3.0. Toxicology Mechanisms and Methods 2025;35(1):32-42 doi: 10.1080/15376516.2024.2382815.
33. Borba Joyce VB, Alves Vinicius M, Braga Rodolpho C, et al. STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity. Environmental Health Perspectives;130(2):027012 doi: 10.1289/EHP9341.
34. Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic acids research 2014;42 doi: 10.1093/nar/gku293.
35. DHONGADE S. APPLICATION OF PASS AS AN EFFECTIVE DRUG DESIGNING TOOL. Reviews of Literature• Volume 2013;1(1).
36. Filimonov D, Lagunin A, Poroikov V. Prediction of activity spectra for substances using new local integrative descriptors. QSAR and Molecular Modelling in Rational Design of Bioactive Molecules. Esin Aki Sener, Ismail Yalcin Eds., Ankara (Turkey) 2005:98-99.
37. Lagunin A, Stepanchikova A, Filimonov D, Poroikov V. PASS: Prediction of activity spectra for biologically active substances. Bioinformatics (Oxford, England) 2000;16:747-8 doi: 10.1093/bioinformatics/16.8.747.
38. Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotechnol 2007;25(2):197-206 doi: 10.1038/nbt1284.
39. Abdulhakeem Mansour Alhasbary A, Hashimah Ahamed Hassain Malim N, Zuraidah Mohamad Zobir S. Exploring natural products potential: A similarity-based target prediction tool for natural products. Computers in Biology and Medicine 2025;184:109351 doi: https://doi.org/10.1016/j.compbiomed.2024.109351.
40. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA. An Unlikely Sugar Substrate Site in the 1.65 Å Structure of the Human Aldose Reductase Holoenzyme Implicated in Diabetic Complications. Science 1992;257(5066):81-84 doi: doi:10.1126/science.1621098.
41. Suriyeni D, Mukarromah Z, Ridho MR, Ridho MA. Eksplorasi Molecular Docking Senyawa Flavonoid Orthosiphon Stamineus B. Reseptor Enzim Siklooksigenase (COX) Sebagai Antiinflamasi. Blantika: Multidisciplinary Journal 2024;2(8).
42. Ounthaisong U, Tangyuenyongwatana P. Cross-docking study of flavonoids against tyrosinase enzymes using PyRx 0.8 virtual screening tool. TJPS 2017;41(2017).
43. Rajab MS. In silico larvicidal activity study of six limonoids against mosquito larvae (Aedes aegypti L.) ecdysone receptor protein. Sciences of Phytochemistry 2024;3(1):20-26.
44. Zhao Y, Hou Y, Ren J, et al. Phenotypic characteristics of taurodontism and a novel WNT10A variant in non-syndromic oligodontia family. Archives of Oral Biology 2023;154:105759.
45. Ali Kharl H, Nadeem H, Khan A, et al. Synthesis, Molecular Docking, and Investigation of Enzyme Inhibition Activities of Benzimidazole-Pyrazole Hybrids. J Vis Exp 2025;1.
46. Wu F, Zhou Y, Li L, et al. Computational Approaches in Preclinical Studies on Drug Discovery and Development. Frontiers in Chemistry 2020;Volume 8 - 2020 doi: 10.3389/fchem.2020.00726.
47. López-Blanco JR, Aliaga JI, Quintana-Ortí ES, Chacón P. iMODS: internal coordinates normal mode analysis server. Nucleic Acids Res 2014;42(Web Server issue):W271-6 doi: 10.1093/nar/gku339 [published Online First: 20140425].
1. Schnall S, Benton J, Harvey S. With a Clean Conscience:Cleanliness Reduces the Severity of Moral Judgments. Psychological Science 2008;19(12):1219-22 doi: 10.1111/j.1467-9280.2008.02227.x.
2. Rauf A, Khan MU, Akram Z, et al. Lipoxygenase inhibitory potential of secondary metabolites isolated from Pistacia integerrima: a comprehensive in vitro analysis integrating molecular docking, ADMET and DFT studies. Tradit Med Res 2025;10:52–57 doi: https://doi.org/10.53388/TMR20241203001.
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11. Tammali R, Srivastava SK, Ramana KV. Targeting aldose reductase for the treatment of cancer. Curr Cancer Drug Targets 2011;11(5):560-71 doi: 10.2174/156800911795655958.
12. Zognjani B, Nixha AR, Duran HE, et al. N-substituted phthalimide–carboxylic acid hybrids as dual-targeted aldose reductase inhibitors: Synthesis, mechanistic insights, and cancer-relevant profiling. Bioorganic Chemistry 2025;163:108788 doi: https://doi.org/10.1016/j.bioorg.2025.108788.
13. Penning TM. Aldo-Keto Reductase Regulation by the Nrf2 System: Implications for Stress Response, Chemotherapy Drug Resistance, and Carcinogenesis. Chem Res Toxicol 2017;30(1):162-76 doi: 10.1021/acs.chemrestox.6b00319 [published Online First: 20161116].
14. Penning TM, Jonnalagadda S, Trippier PC, Rižner TL. Aldo-Keto Reductases and Cancer Drug Resistance. Pharmacol Rev 2021;73(3):1150-71 doi: 10.1124/pharmrev.120.000122.
15. Hu Q, Bian Q, Rong D, et al. JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens. Frontiers in Bioengineering and Biotechnology 2023;11 doi: 10.3389/fbioe.2023.1110765.
16. Syamprasad N, Rajdev B, Jain S, et al. Pivotal role of AKR1B1 in pathogenesis of colitis associated colorectal carcinogenesis. International immunopharmacology 2023;119:110145 doi: 10.1016/j.intimp.2023.110145.
17. Balestri F, Moschini R, Mura U, Cappiello M, Del Corso A. In Search of Differential Inhibitors of Aldose Reductase. Biomolecules 2022;12(4) doi: 10.3390/biom12040485 [published Online First: 20220322].
18. Khalid M, Petroianu G, Adem A. Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives. Biomolecules 2022;12 doi: 10.3390/biom12040542.
19. Zanoni M, Bravaccini S, Fabbri F, Arienti C. Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance. Frontiers in Medicine 2022;9 doi: 10.3389/fmed.2022.795762.
20. Lyon RC, Li D, McGarvie G, Ellis EM. Aldo-keto reductases mediate constitutive and inducible protection against aldehyde toxicity in human neuroblastoma SH-SY5Y cells. Neurochem Int 2013;62(1):113-21 doi: 10.1016/j.neuint.2012.10.007 [published Online First: 20121022].
21. Cho SJ, Kang KA, Piao MJ, et al. 7,8-Dihydroxyflavone Protects High Glucose-Damaged Neuronal Cells against Oxidative Stress. Biomol Ther (Seoul) 2019;27(1):85-91 doi: 10.4062/biomolther.2018.202.
22. Srivastava SK, Yadav UC, Reddy AB, et al. Aldose reductase inhibition suppresses oxidative stress-induced inflammatory disorders. Chem Biol Interact 2011;191(1-3):330-8 doi: 10.1016/j.cbi.2011.02.023 [published Online First: 20110224].
23. Shoeb M, Yadav UC, Srivastava SK, Ramana KV. Inhibition of aldose reductase prevents endotoxin-induced inflammation by regulating the arachidonic acid pathway in murine macrophages. Free Radic Biol Med 2011;51(9):1686-96 doi: 10.1016/j.freeradbiomed.2011.07.024 [published Online First: 20110805].
24. Rauf A, Khan M, Akram Z, et al. Lipoxygenase inhibitory potential of secondary metabolites isolated from Pistacia integerrima: a comprehensive in vitro analysis integrating molecular docking, ADMET and DFT studies. Tradit Med. Res. 2025;10:52.
25. Wu T-G, Ke Y, Tang H, Liao C, Li J, Wang L. Fidarestat induces glycolysis of NK cells through decreasing AKR1B10 expression to inhibit hepatocellular carcinoma. Molecular Therapy Oncolytics 2021;23:420-31 doi: 10.1016/j.omto.2021.06.005.
26. Zhao JX, Yuan YW, Cai CF, et al. Aldose reductase interacts with AKT1 to augment hepatic AKT/mTOR signaling and promote hepatocarcinogenesis. Oncotarget 2017;8(40):66987-7000 doi: 10.18632/oncotarget.17791 [published Online First: 20170510].
27. Bailly C. Moving toward a new horizon for the aldose reductase inhibitor epalrestat to treat drug-resistant cancer. European Journal of Pharmacology 2022;931:175191 doi: https://doi.org/10.1016/j.ejphar.2022.175191.
28. Metwaly AM, Saleh MM, Alsfouk BA, et al. Anti-virulence potential of patuletin, a natural flavone, against Staphylococcus aureus: In vitro and In silico investigations. Heliyon 2024;10(2).
29. Metwaly A, Saleh MM, Alsfouk A, et al. In silico and in vitro evaluation of the anti-virulence potential of patuletin, a natural methoxy flavone, against Pseudomonas aeruginosa. PeerJ 2024;12:e16826.
30. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports 2017;7(1):42717 doi: 10.1038/srep42717.
31. Pires DEV, Blundell TL, Ascher DB. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. Journal of Medicinal Chemistry 2015;58(9):4066-72 doi: 10.1021/acs.jmedchem.5b00104.
32. Banerjee P, Ulker O, Ozkan I, Ulker OC. The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox- 3.0. Toxicology Mechanisms and Methods 2025;35(1):32-42 doi: 10.1080/15376516.2024.2382815.
33. Borba Joyce VB, Alves Vinicius M, Braga Rodolpho C, et al. STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity. Environmental Health Perspectives;130(2):027012 doi: 10.1289/EHP9341.
34. Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic acids research 2014;42 doi: 10.1093/nar/gku293.
35. DHONGADE S. APPLICATION OF PASS AS AN EFFECTIVE DRUG DESIGNING TOOL. Reviews of Literature• Volume 2013;1(1).
36. Filimonov D, Lagunin A, Poroikov V. Prediction of activity spectra for substances using new local integrative descriptors. QSAR and Molecular Modelling in Rational Design of Bioactive Molecules. Esin Aki Sener, Ismail Yalcin Eds., Ankara (Turkey) 2005:98-99.
37. Lagunin A, Stepanchikova A, Filimonov D, Poroikov V. PASS: Prediction of activity spectra for biologically active substances. Bioinformatics (Oxford, England) 2000;16:747-8 doi: 10.1093/bioinformatics/16.8.747.
38. Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotechnol 2007;25(2):197-206 doi: 10.1038/nbt1284.
39. Abdulhakeem Mansour Alhasbary A, Hashimah Ahamed Hassain Malim N, Zuraidah Mohamad Zobir S. Exploring natural products potential: A similarity-based target prediction tool for natural products. Computers in Biology and Medicine 2025;184:109351 doi: https://doi.org/10.1016/j.compbiomed.2024.109351.
40. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA. An Unlikely Sugar Substrate Site in the 1.65 Å Structure of the Human Aldose Reductase Holoenzyme Implicated in Diabetic Complications. Science 1992;257(5066):81-84 doi: doi:10.1126/science.1621098.
41. Suriyeni D, Mukarromah Z, Ridho MR, Ridho MA. Eksplorasi Molecular Docking Senyawa Flavonoid Orthosiphon Stamineus B. Reseptor Enzim Siklooksigenase (COX) Sebagai Antiinflamasi. Blantika: Multidisciplinary Journal 2024;2(8).
42. Ounthaisong U, Tangyuenyongwatana P. Cross-docking study of flavonoids against tyrosinase enzymes using PyRx 0.8 virtual screening tool. TJPS 2017;41(2017).
43. Rajab MS. In silico larvicidal activity study of six limonoids against mosquito larvae (Aedes aegypti L.) ecdysone receptor protein. Sciences of Phytochemistry 2024;3(1):20-26.
44. Zhao Y, Hou Y, Ren J, et al. Phenotypic characteristics of taurodontism and a novel WNT10A variant in non-syndromic oligodontia family. Archives of Oral Biology 2023;154:105759.
45. Ali Kharl H, Nadeem H, Khan A, et al. Synthesis, Molecular Docking, and Investigation of Enzyme Inhibition Activities of Benzimidazole-Pyrazole Hybrids. J Vis Exp 2025;1.
46. Wu F, Zhou Y, Li L, et al. Computational Approaches in Preclinical Studies on Drug Discovery and Development. Frontiers in Chemistry 2020;Volume 8 - 2020 doi: 10.3389/fchem.2020.00726.
47. López-Blanco JR, Aliaga JI, Quintana-Ortí ES, Chacón P. iMODS: internal coordinates normal mode analysis server. Nucleic Acids Res 2014;42(Web Server issue):W271-6 doi: 10.1093/nar/gku339 [published Online First: 20140425].
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Jan 20, 2026
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Mahwish Fatima, Syeda Afroz, Arooj shafiq, Abdul Hameed, Paras Jawaid, Mati Ur Rehman, Jawad Zahid, Syeda Izma Hashmi, & Aisha Hasan. (2026). ALDOSE REDUCTASE INHIBITORY POTENTIAL OF PATULETIN: A COMPREHENSIVE IN VITRO ANALYSIS INTEGRATING ADMET, MOLECULAR DOCKING, AND MD STUDIES FOR PREDICTED UPSTREAM ANTICANCER PATHWAY. Journal of Population Therapeutics and Clinical Pharmacology, 33(1), 3966-3991. https://doi.org/10.69980/36jygs38
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Author Biographies
Mahwish Fatima
Department of Pharmacology,Faculty of Pharmacy and Pharmaceutical Sciences,University of Karachi, Pakistan.
Syeda Afroz
Department of Pharmacology,Faculty of Pharmacy and Pharmaceutical Sciences,University of Karachi, Pakistan.
Arooj shafiq
Department of Biological and Biomedical sciences, Aga Khan university karachi, Pakistan.
Abdul Hameed
Department of Molecular Medicine, Ziauddin University, karachi, Pakistan.
Paras Jawaid
Department of Biological and Biomedical sciences, Aga Khan university karachi, Pakistan.
Mati Ur Rehman
Department of Biological and Biomedical sciences, Aga Khan university karachi, Pakistan.
Jawad Zahid
Department of Pharmacology,Faculty of Pharmacy and Pharmaceutical Sciences,University of Karachi, Pakistan.
Syeda Izma Hashmi
Department of Physical Therapy ,University of Karachi, Pakistan.
Aisha Hasan
Department of Pharmacology,Faculty of Pharmacy and Pharmaceutical Sciences,University of Karachi, Pakistan.
How to Cite
Mahwish Fatima, Syeda Afroz, Arooj shafiq, Abdul Hameed, Paras Jawaid, Mati Ur Rehman, Jawad Zahid, Syeda Izma Hashmi, & Aisha Hasan. (2026). ALDOSE REDUCTASE INHIBITORY POTENTIAL OF PATULETIN: A COMPREHENSIVE IN VITRO ANALYSIS INTEGRATING ADMET, MOLECULAR DOCKING, AND MD STUDIES FOR PREDICTED UPSTREAM ANTICANCER PATHWAY. Journal of Population Therapeutics and Clinical Pharmacology, 33(1), 3966-3991. https://doi.org/10.69980/36jygs38
