Microwave-assisted synthesis, biological evaluation and molecular docking studies of new coumarin-based 1,2,3-triazoles

Abstract

Coumarin-based 1,4-disubstituted 1,2,3-triazole derivatives were synthesized using a highly efficient, ecofriendly protocol via a copper(I)-catalyzed click reaction between various substituted arylazides and terminal alkynes. The synthetic route was easy to access and gave excellent yields under microwave irradiation conditions compared to the conventional heating route. The structures of all the compounds were characterized by IR, 1 H NMR, 13 C NMR spectroscopy and mass spectrometry. All the synthesized compounds were screened for their in vitro antimicrobial, antioxidant and anti-inflammatory activities; among all compounds, 8a, 8j, 8k and 8l exhibited better results with respect to standard drugs.Furthermore, molecular docking studies have been carried out with PDB IDs 2VCX (anti-inflammatory), 3VXI (antioxidant), 4GEE (antimicrobial) and 2XFH (antifungal) using the Glide module of the Schrödinger suite. The final compounds 8d, 8e, 8h, and 8k showed the highest hydrogen bond interactions with His-88 and Val-191 proteins and with water in all the proteins.

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

“…The in vitro antifungal activity was tested against Aspergillus niger, Aspergillus flavus and Fusarium oxysporum by using the disc diffusion method and the results were compared with those of clotrimazole, the reference drug. Compounds 63-68 ( Figure 26), characterized by the presence of a para-substituted phenyl moiety, directly linked to the triazole ring, showed comparable activity in respect to the reference compound clotrimazol [101,102]. The antifungal potency of coumarin-based triazoles against other fungal strains in addition to Candida species had been evaluated by Dharavath and colleagues in 2020.…”

Application of triazoles in the structural modification of natural products

“…Coumarin-based 1,4-disubstituted 1,2,3-triazole derivatives were synthesised by Dharavath et al. 154 All of the synthesised compounds were screened for their in vitro scavenging activity. The IC 50 values ranged from 338.48 µM/mL to 0.064 µM/mL and varied widely compared to that of standard ascorbic acid (IC 50 value 1.46 µM/mL).…”

“…Coumarin-triazole derivatives not only possess anticancer activity 58 , 68 , 70 , 90–93 , anti-inflammatory activity 115 , antibacterial activity 128 , 129 , antifungal activity 133 , antimalarial activity 140 , antioxidant activity 154 , and anti-Alzheimer’s activity 156–164 , but also they exhibit pancrelipase inhibitory activity 167 . Kahveci et al.…”

Microwave assisted synthesis of 4‐methyl‐3‐arylpyrano[2,3‐f]chromen‐2(8H)‐one derivatives, evaluation of antiproliferative, and antimicrobial activities

“…using anhydrous K 2 CO 3 as a base and dry propanone as a solvent. [ 16 ] Finally the reaction conditions were successfully optimized with chromenone 3 (1 eq. ), 1‐(2,3‐dihydro‐1 H ‐imidazol‐1‐yl)‐2‐phenylethanone 6 ( a ‐ h ) using anhydrous K 2 CO 3 as a base and dry propanone as a solvent.…”