Synthesis, characterization, DFT and biological study of new methylene thio-linked coumarin derivatives

Abstract

A series of new methylene thio-linked coumarin derivatives 3(a-j) were synthesized by the reaction substituted 4-(bromomethyl)-2H-chromen-2-one with different heterocyclic mercapto compounds via SN2 reaction in presence of K2CO3 as a catalyst. The structural conformation of synthesized compounds was performed using different spectroscopic techniques like FT-IR,1H NMR, 13C NMR, and LC-MS. DFT studies were performed to determine the electronic properties and vibrational frequencies for all the synthesized compounds. The synthesized compounds were evaluated for in vitro anti-cancer and anti-tuberculosis activityin vitro anticancer activity revealed that 3g molecule with methoxy substituted benzimidazole ring showed an IC50 value of 0.18 µM which is a more effective compound against MCF-7 cell line. Tuberculosis activity against, the H37Rv strain showed the moderate result. The molecular docking studies revealed that 3h molecule containing benzoxazole ring showed the highest binding affinity -9.4 kcal/mol and other molecules showed promising results compared to standard isoniazid. Molecular docking was performed with protein to study the binding mode of designed compounds.