Computational Studies and Antimicrobial Activity of 1-(benzo[d]oxazol-2-yl)-3,5-Diphenylformazan Derivatives

Mazen Almehmadi; Ahad Amer Alsaiari; Mamdouh Allahyani; Abdulaziz Alsharif; Abdulelah Aljuaid; Supriyo Saha; Mohammad Asif

doi:10.2174/1573409919666230703103135

Computational Studies and Antimicrobial Activity of 1-(benzo[d]oxazol-2-yl)-3,5-Diphenylformazan Derivatives

Curr Comput Aided Drug Des. 2023 Jul 3. doi: 10.2174/1573409919666230703103135. Online ahead of print.

Authors

Mazen Almehmadi¹, Ahad Amer Alsaiari¹, Mamdouh Allahyani¹, Abdulaziz Alsharif¹, Abdulelah Aljuaid¹, Supriyo Saha², Mohammad Asif³

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
² Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, Uttarakhand 248007, India.
³ Era College of Pharmacy, Era University, Lucknow 226003, Uttar Pradesh, India.

PMID: 37403393
DOI: 10.2174/1573409919666230703103135

Abstract

Background: Due to the biological importance of the benzoxazole derivatives, some 1-(benzo[d]oxazol-2-yl)-3,5-diphenyl-formazans (4a-f) were synthesized and screened for in-silico studies and in-vitro antibacterial activity.

Methods: The benzo[d]oxazole-2-thiol (1) was prepared by reacting with 2-aminophenol and carbon disulfide in the presence of alcoholic potassium hydroxide. Then 2-hydrazinylbenzo[d]oxazole (2) was synthesized from the reaction of compound 1 with hydrazine hydrate in the presence of alcohol. Compound 2 was reacted with aromatic aldehydes to give Schiff base, 2-(2-benzylidene-hydrazinyl)benzo[d]oxazole derivatives (3a-f). The title compounds, formazan derivatives (4a-f), were prepared by a reaction of benzene diazonium chloride. All compounds were confirmed by their physical data, FTIR, 1H-NMR, and 13CNMR spectral data. All the prepared title compounds were screened for in-silico studies and in-vitro antibacterial activity on various microbial strains.

Results: Molecular docking against the 4URO receptor demonstrated that molecule 4c showed a maximum dock score of (-) 8.0 kcal/mol. MD simulation data reflected the stable ligand-receptor interaction. As per MM/PBSA analysis, the maximum free binding energy of (-) 58.831 kJ/mol was exhibited by 4c. DFT calculation data confirmed that most of the molecules were soft molecules with electrophilic nature.

Conclusion: The synthesized molecules were validated using molecular docking, MD simulation, MMPBSA analysis, and DFT calculation. Among all the molecules, 4c showed maximum activity. The activity profile of the synthesized molecules against tested micro-organisms was found to be 4c>4b>4a>4e>4f>4d.

Keywords: Keywords: Benzoxazole derivatives; antibacterial activity.; diazonium salt; formazan.