Title:DFT and In-silico Investigations, along with In-vitro Antitumor and Antimicrobial
Assessments of Pharmacological Molecules
Volume: 20
Issue: 5
Author(s): Mosa H. Alsehli, Daya S. Seth, Mohamed S.A. El-Gaby, Rawda M. Okasha, Mohamed Hagar, Tarek H. Afifi*Arshi Naqvi*
Affiliation:
- Department of Chemistry, College of Science, Taibah University, Al Madina Al Munawwara, Kingdom of Saudi Arabia
- Department of Chemistry, College of Science, Taibah University, Al Madina Al Munawwara, Kingdom of Saudi Arabia
- Chemistry Department, St. John’s College, Agra (U.P)-282001, India
Keywords:
Coumarin, benzocoumarin, molecular docking, in-vitro screenings, DFT calculations. antitumor.
Abstract:
Background: Molecules bearing an active methylene bridge are one of the most fruitful
and remarkable precursors that have been incorporated into 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 result from their structural diversity and discrete
reactivity.
Methods: The present report endeavors to synthesize, characterize, and in-vitro evaluate several
novel propanoic acids, 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 (azocoumarin)
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
lines and the hemolytic effect on RBCs.
Conclusion: The in-silico ADMET studies of the synthesized compounds revealed moderate to
good -likeness, high gastro intestinal (GI) absorption, and inhibiting 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 functional
theory (DFT) theoretical calculations were performed to calculate the energy levels of the FMOs
and their energy gaps, dipolemoment, andmolecular electrostatic potential. Such parameters, along
with the physicochemical parameters, could be a good tool to confirm biological activity.
