Synthesis, in-Silico studies, and in-Vitro bio-evaluation of new bi-thiacoumarins

Abstract

In the present study, two new bi-thiacoumarin derivatives viz. 3-(7-hydroxy-2-oxo-2H-chromen-3-yl)-2-thioxo-2H-thiochromen-7-yl) (4-methoxyphenyl) phosphinothioate (Tc01) and 4-hydroxy-4′-mercapto-2′-thioxo-2H,2'H-[3,3′-bichromen]-2-one (Tc02) have been synthesized via lawesson reagent through concerted cycloaddition and cycloreversion reaction. Compounds were characterized by M.P, UV, FTIR, 1H NMR, 13C NMR, and EIMS. The synthesized compounds were evaluated by in-Vitro anticoagulant, antibacterial, anticancer and cytotoxicity assays. In-Silico docking studies were performed to instigate the binding affinity towards target that showed moderate interaction through hydrogen bonding, hydrophobic and pi-pi interaction. Compounds Tc01, Tc02 exhibited promising activity towards antibacterial and anticoagulant assays. The moderate activity was showed by Tc01 towards MTT assay (Hela cell line and BJ cell line) while Tc02 remained inactive. The antioxidant activity was also performed by DPPH assay with very significant %age inhibition IC50 values. Similarly, the alpha-amylase inhibition assay (antidiabetic activity) also exhibited significant activity indicating remedial potential.