Design, synthesis and biological evaluation of some novel diastereoselective β-lactams bearing 2-mercaptobenzothiazole and benzoquinoline

Abstract

We report the synthesis of some novel β-lactam hybrids of 2-mercaptobenzothiazole and benzoquinoline. These compounds were synthesized by a [2 + 2]-cycloaddition reaction of imines 8a-d and ketenes derived from substituted acetic acids. The reaction was totally diastereoselective leading exclusively to the formation of cis-β-lactams 10a-m. All products were obtained in good to excellent yields and their structures were established based on IR, 1 H NMR, 13 C NMR spectral data and elemental analysis. Schiff bases 8a-d and β-lactam hybrids 10a-m were evaluated for antimicrobial activities against six bacterial species. The minimum inhibitory concentration (MIC) values indicate that two of the β-lactams, 10k and 10m, have good activities against the two Gram-negative bacteria, E. coli and P. aeruginosa, while three of the Schiff bases, 8a-c, are active against P. aeruginosa and the Gram-positive pathogen S. aureus. The molecular and cellular basis for these observed antibacterial properties are not determined. Moreover, the five most active compounds showed acceptably low cytotoxicity (less than 25% cell growth inhibition after 72 h of incubation) against the MCF-7 cell line, and below 10% in vitro hemolytic activity at 50 and 200 µM concentrations. These results suggest a need for further inquiry into the reason for why these compounds are bioactive, and as to what their full biological activities and antibiotic potential may be. The cis stereochemistry of β-lactam 10a was confirmed by X-ray crystallographic studies.