Biological Activity and Molecular Docking Studies of Curcumin-Related α,β-Unsaturated Carbonyl-Based Synthetic Compounds as Anticancer Agents and Mushroom Tyrosinase Inhibitors

• Published in: Journal of agricultural and food chemistry Vol. 62; no. 24; pp. 5538 - 5547
• Main Authors: Bukhari, Syed Nasir Abbas, Jantan, Ibrahim, Unsal Tan, Oya, Sher, Muhammad, Naeem-ul-Hassan, M, Qin, Hua-Li
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18-06-2014; American Chemical Society, Books and Journals Division
• Subjects: Agaricales - enzymology; antineoplastic agents; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Chemical Phenomena; curcumin; Curcumin - pharmacology; cytotoxicity; Drug Discovery; enzymatic browning; enzyme inhibitors; Enzyme Inhibitors - pharmacology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; fruits; HT29 Cells; Humans; MCF-7 Cells; Models, Molecular; Molecular Docking Simulation; molecular models; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; mushrooms; neoplasms; Structure-Activity Relationship; structure-activity relationships; synthesis; melanogenesis; Curcuma longa; cytotoxicity; antibrowning
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf501145b

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.