Molecular docking, synthesis and evaluation of the antimicrobial, antiproliferative, and antioxidant properties of β-lactam bisindoles

Abstract

A series of novel bis(indolyl)methane-β-lactam hybrids has been efficiently synthesized by a [2 + 2]-cycloaddition reaction of imines 5a-c with ketenes derived from substituted acetic acids. All cycloadducts were obtained in good to excellent yields, and their structures were established based on FT-IR, 1H NMR, 13C NMR spectral data, and elemental analysis. The cycloadditions were diastereoselective, leading exclusively to the formation of cis-β-lactams 6a-l. These compounds were evaluated for antibacterial, antioxidant, and antiproliferative activities. All compounds (6a-l) were screened against the gram-positive S. aureus (ATCC 25923) and gram-negative E. coli (ATCC 25922), P. aeruginosa (9027) bacteria. Among the series, compounds 6b-e and 6g-j exhibited significant levels of antibacterial activity, comparable to gentamycin (the control standard). β-Lactams 6a-l were also screened for antiproliferative activities against the MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. Three compounds (6j-k) displayed promising antiproliferative activity against MCF-7. Also, an evaluation of the antioxidant potential of each of the compounds, performed by diphenylpicrylhydrazyl (DPPH) assay, indicated that 6b, 6e-h, and 6j have strong free radical scavenging activity.