IN-SILICO DESIGN AND DOCKING STUDY OF SOME 4-(10-ACETYL-10H-PHENO-THIAZINES-3-YL)-1-PHENYLAZETIDIN-2-ONE DERIVATIVESAbstract
Background: The current study used computational approaches to investigate the molecular, physicochemical and drug-like properties of some 4-(10-acetyl-10H-phenothiazines-3-yl)-1-phenylazetidin-2-one derivatives. Methods: The structures of the compounds were drawn using Chemdraw ultra12 and smiles were generated using ACD chem sketch software. The physicochemical and molecular properties were calculated using the OSIRIS data warrior, and Toxicity potential, pharmacokinetic profile and medicinal chemistry aspects were determined by Swiss ADME tools. The docking analysis was carried out by mCule for the antimicrobial and anti-inflammatory profiles. The compounds were targeted for beta-lactamase, peptidoglycan hydroxylase, Cyclo-oxygenase-1 and 2 inhibitions. Result: All the compounds exhibited moderate to good drug likeliness and pharmacokinetic potential. The molecules showed good bioactivity scores against enzyme receptors. The ADMET prediction showed PGP and CYP-inhibitory effects with the least toxic profile. The docking analysis showed good binding affinity toward beta-lactamase, peptidoglycan hydroxylase and cycloxygenase-1 enzymes. Conclusion: The compounds showed good drug likeliness properties along with good toxicity potential and pharmacokinetic profiles. From docking analysis, it was found that all the molecules had a good binding affinity for beta-lactamase enzymes and peptidoglycan hydroxylase enzymes. The results also showed a more strong COX2 binding affinity than COX-1.
Sandip Sen *, Bairam Ravindar, Sirikonda Jala and Laxmi Dharabonia
Department of Pharmaceutical Chemistry, School of Pharmacy, Gurunanak Institute Technical Campus, Ibrahimpattnam, Telangana, India.
29 November 2021
27 January 2022
27 April 2022
01 August 2022