Antimicrobial Action of Arylsulfonamides Bearing (aza)Norbornane and Related Motifs: Evaluation of New Promising Anti-MRSA Agents

Abstract Arylsulfonamides bearing (aza)norbornane and related motifs were evaluated for: 1) antimicrobial activity toward five key ESKAPE pathogenic bacteria, one Gram‐positive bacteria methicillin‐resistant Staphylococcus aureus (MRSA, ATCC 43300), four Gram‐negative bacteria, Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Acinetobacter baumannii (ATCC 19606), and Pseudomonas aeruginosa (ATCC 27853), and 2) antifungal activity toward two pathogenic fungal strains - Candida albicans (ATCC 90028) and Cryptococcus neoformans var. Grubii (H99; ATCC 208821). Four compounds with 4-nitrobenzenesulfonamide motif (VP-4556, VP-4604, VP-4605, and VP-4509) demonstrated high toxicity toward methicillin‐resistant Staphylococcus aureus (ATCC 43300). These compounds also possessed high antibacterial activity toward gram-negative bacteria P. aeruginosa (ATCC9027). According to the results of toxicity studies of the compounds to HEK-293, HaCaT, Balb/c 3T3, red blood cells and normal mitogen-activated lymphocytes, three compounds - VP-4556, VP-4604 and VP-4509 - bearing azanorbornene, octahydro-3,5-methanocyclopenta[b]pyrrole and bio-isosteric piperidine motifs were selected for further studies as biocompatible agents with promising antimicrobial activity.