title: Biological activity and molecular docking studies of curcumin-related α,β-unsaturated carbonyl-based synthetic compounds as anticancer agents and mushroom tyrosinase inhibitors.
abstract: Hyperpigmentation in human skin and enzymatic browning in fruits, which are caused by tyrosinase enzyme, are not desirable. Investigations in the discovery of tyrosinase enzyme inhibitors and search for improved cytotoxic agents continue to be an important line in drug discovery and development. In present work, a new series of 30 compounds bearing α,β-unsaturated carbonyl moiety was designed and synthesized following curcumin as model. All compounds were evaluated for their effects on human cancer cell lines and mushroom tyrosinase enzyme. Moreover, the structure-activity relationships of these compounds are also explained. Molecular modeling studies of these new compounds were carried out to explore interactions with tyrosinase enzyme. Synthetic curcumin-like compounds (2a-b) were identified as potent anticancer agents with 81-82% cytotoxicity. Five of these newly synthesized compounds (1a, 8a-b, 10a-b) emerged to be the potent inhibitors of mushroom tyrosinase, providing further insight into designing compounds useful in fields of food, health, and agriculture.
authors.affiliation: Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia , Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Syed Nasir Abbas
authors.initials: SN
authors.lastname: Bukhari
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Jantan
authors.forename: Oya
authors.initials: O
authors.lastname: Unsal Tan
authors.forename: Muhammad
authors.initials: M
authors.lastname: Sher
authors.forename: M
authors.initials: M
authors.lastname: Naeem-Ul-Hassan
authors.forename: Hua-Li
authors.initials: HL
authors.lastname: Qin
mesh_terms: D000363:Agaricales / Q000201:enzymology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D003474:Curcumin / Q000494:pharmacology*; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D014442:Monophenol Monooxygenase; D003474:Curcumin