Design, synthesis, characterization, antimicrobial evaluations and molecular docking studies of 5-(phenylcarbamoyl)pentylselenyl tethered ester, acid and trans-β-lactams

Herein, we unveil the utility of bis(5-phenylcarbamoylpentyl)diselenide 2 for obtaining unique seleno-ester viz ethyl 2-(5-(phenylcarbamoyl)pentylselenyl)ethanoate 3 and further transformation of 3 to 2-(5-(phenylcarbamoyl)pentylselenyl)ethanoic acid 4. Next, time-efficient (complete in 15 min.) and stereoselective synthesis of trans-3-((5-phenylcarbamoyl)pentylselenyl)-β-lactams 6a-d (52-78% yields) starting from seleno-acid 4 and substituted imines 5a-d has been reported with relevant characterization data (FT-IR, FT-NMR (¹H, ¹³C), CHN elemental analysis). In vitro antibacterial and antifungal biological evaluation and in silico molecular docking studies exhibit a profound dependence on the nature of the functionality (functionalized selenyl- /ester / acid / β-lactam) anchored to 5-(phenylcarbamoyl)pentylselenyl chain. In vitro antimicrobial studies evidenced seleno-ester 3 and trans-seleno-β-lactam 6c (incorporating p-methoxyphenyl substituents both at N1 and C4 atoms of the β-lactam ring) to be active against all tested gram positive bacterial (S. aureus, B. subtilis), gram negative bacterial (E. coli, P. aeruginosa) and fungal (C. albicans) species exhibiting 9-20 mm and 8-12 mm diameter of inhibition zones. trans-β-Lactam 6b (with C4-phenyl and N1-p-methylphenyl groups) exhibited maximum inhibition zone diameter (14 mm against S. aureus) amongst trans-6a-d. Molecular docking results of ligand binding affinity are observed to be in well agreement with the in vitro antimicrobial results making these seleno-compounds potential candidates of medicinal importance.