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.

Synthesis and mechanistic studies of curcumin analog‐based oximes as potential anticancer agents

“…In this study, we extended our previously reported work by synthesizing new oxime derivatives of most potent curcumin‐like α, β‐unsaturated carbonyl‐based compounds reported in an earlier study. The anticancer activity of all new oxime derivatives was assessed and the derivatives were subjected to further studies to investigate their effects on tubulin polymerization, EGFR‐TK kinases, and BRAF V600E and were tested in vitro for the reversal of efflux‐mediated resistance developed by the cancer cells.…”

“…The previously reported method by our group was used to synthesize new oxime analogs using most potent α, β‐unsaturated carbonyl‐based compounds ( 1–8 ) as precursors. Each selected compound (1 mmol) was reacted to hydroxylamine hydrochloride (2 mmol) in 10 ml of ethanol to produce the corresponding oxime ( 1a–8a ).…”

“…3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT) assay was conducted to determine the effect of new oxime compounds on mammary epithelial cells (MCF‐10A) . Different types of cell lines including HT‐29 (colon cancer), PC‐3 (prostate cancer), A‐549 (epithelial), Panc‐1 (pancreas cancer), MCF‐7 (breast cancer), H‐460 (lung cancer), and PaCa‐2 (pancreatic carcinoma) were used to perform PI fluorescence assay to study the antiproliferative efficacy of compounds. Tubulin Polymerization Assay Kit (Cytoskeleton Inc., Denver, CO, USA), which works on the principle of fluorescent reporter enhancement, was used to investigate the effect of compounds on tubulin polymerization.…”

“…The anticancer characteristics of curcumin have been under the spotlight from the past 3–4 decades. Lately, we reported a series of thirty compounds bearing α, β‐carbonyl moiety as present in curcumin for potential use in agriculture, food, cosmetics, and medicine industry . The effect of synthesized compounds on seven different human cancer cell lines was assessed.…”

Curcumin could reduce the monomer of TTR with Tyr114Cys mutation via autophagy in cell model of familial amyloid polyneuropathy

“…Curcumin and its analogs have demonstrated a protective effect in many diseases involving antimicrobial, antitubercular,8 and anticancer mechanisms,9 and they can also modulate innate immunity 10. Of note, curcumin has been shown to promote autophagy 11.…”