An efficient, catalyst-free, one-pot synthesis of 4H-chromene derivatives and investigating their biological activities and mode of interactions using molecular docking studies

WOS: 000504448700055
In the present study, the design and development of an efficient and green method for the synthesis of dialkyl 4-hydroxy-4H-chromene-2,3-dicarboxylate derivatives together with their biological evaluation are reported. A series of 4H-chromenes were synthesized in the presence of 1-hexyl-3-methylimidazolium bromide ([HMIM]Br) as an environmentally friendly media, without using any organic and toxic solvent and catalyst. The reaction was rapid and was conducted at room temperature with high-to-excellent yields. The antiproliferative potential of the synthesized compounds was evaluated against human lung (A549), breast (MCF-7), and colon (HT-29) cancerous cell lines by adopting MTT method. The tested chromenes showed cytotoxicity in the range of 8.8-82.3% against A549 cells at 200 mu g/mL. Also, chromene derivatives were assessed for tyrosinase and alpha-glucosidase inhibitory activities. Based on IC50 values (2.99-4.39 mM), all chromenes exhibited significant alpha-glucosidase inhibition compared with acarbose (IC50 = 7.90 mM). Furthermore, the ability of the studied compounds to inhibit tyrosinase was evaluated and found to be moderate (IC50 = 3.50-12.20 mM). In silico studies were performed to explore the binding modes of the chromenes at the binding site of alpha-glucosidase and tyrosinase. Molecular docking results revealed the importance of hydrogen bonding, hydrophobic, pi-pi stacking, pi-cation, and metal interactions between the target enzymes and the synthesized compounds. Collectively, the results obtained in the current work indicated that the studied chromenes may be regarded as lead compounds for designing new chemicals potentially effective in conditions such as skin disorders and diabetes mellitus. (C) 2019 Elsevier B.V. All rights reserved.
Ministry of Health and Medical Education; Biotechnology Research Center at Tabriz University of Medical Sciences
The authors would like to acknowledge the Ministry of Health and Medical Education, and also, Biotechnology Research Center at Tabriz University of Medical Sciences for the financial support.