DFT and In-silico Investigations, along with In-vitro Antitumor and Antimicrobial Assessments of Pharmacological Molecules

Abstract

Background: Molecules, bearing an active methylene bridge, are deemed to be one of the most fruitful and remarkable precursors that have been incorporated in the synthetic strategy of an assortment of bioactive compounds. Objective: The reactive methylene derivatives have been endowed with multiple reactions, which target biological and medicinal applications and are resultant from their structural multiplicity and discrete reactivity. Methods: The present report endeavors to synthesize, characterize, and in-vitro evaluate several novel propanoic acid, coumarin, and pyrazole derivatives as antimicrobial and antiproliferative agents. The in-silico molecular docking, physicochemical, pharmacokinetic/ADMET, bioactivity, and drug likeness predictions were conducted for all the synthesized compounds. Results: The highest docking score is -9.9 and -8.3 kcal/mol respectively for compound 9 (azo-coumarin) and 13 (acrylic acid derivative) with the target proteins E. coli topoisomerase II, DNA gyrase subunit B and PI3K p110α domain, respectively. Moreover, this study predicts the synthesized molecules that may inhibit the novel COVID-19, obtained through virtual screenings only, where compounds 9, 13, 14, 17, and 19 came to the limelight with good docking scores i.e more than 8 Kcal/mol. Safety profiling of the most potent compound 9 was utilized against normal cell line and hemolytic effect on RBCs. Conclusion: The in-silico ADMET studies of the synthesized compounds revealed moderate to good drug likeness, high gastro intestinal (GI) absorption, inhibits the Cytochrome CYP2C19 and CYP2C9 and all the derivatives possess non-cancerous nature. The in-vitro screening demonstrated that several of the novel molecules are promising drug candidates. The density function theory (DFT) theoretical calculations were performed to calculate the energy levels of the FMOs and their energy gabs, dipole moment as well as the molecular electrostatic potential. Such parameters along with the physicochemical parameters could be good tool to confirm the biological activity.