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 ve 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, pyrrole and bio-isosteric piperidine motifs were selected for further studies as biocompatible agents with promising antimicrobial activity.

Design and Synthesis of Novel 2‐Acetamido, 6‐Carboxamide Substituted Benzothiazoles as Potential BRAFV600E Inhibitors – In vitro Evaluation of their Antiproliferative Activity

“…Scheme 4 describes the preparation of amines 9 h-k with the phenylene linker connected to the sulfonamido moiety in the order À C 6 H 4 À SO 2 N(H)À R, which is the reverse order compared to amines 9 e-g. They have been prepared by coupling of 4-nitro-benzenesulfonyl chloride (17) with the appropriate amines 18 a-d in the presence of a base to afford the nitro derivatives 19 a-d, [33][34][35][36] followed by reduction of the nitro to the amino group using iron powder and ammonium chloride solution in ethanol for amines 9 i and 9 j or alternatively, SnCl 2 in ethanol under ultrasound irradiation for amines 9 h and 9 k. All new compounds were fully characterized by NMR and high resolution mass spectrometry (HRMS), in which the measured accurate masses corresponded exactly to the proposed formulas. In the 1 H NMR spectra of all final products, the…”

Polyhalogenated 2‐Azabicyclo[2.2.1]heptanes from Polyhaloaldimines and Cyclopentadiene via Cycloaddition and Wagner‐Meerwein Rearrangement

“…2‐Azanorbornanes may be considered as conformationally rigid bridged analoges of cyclopentylamine, piperidine, pyrrolidine and exhibit diverse types of biological activity and reactivity [11,12] . Compound 1 (Figure 1) containing an azanorbornene ring exhibits a pronounced antibacterial activity which is higher than for an analog with a piperidine fragment [8] …”

“…The substituted 2-azabicyclo[2.2.1]hept-5-enes (2-azanorbornenes) are intriguing objects for the study of their biological activity and prospective building blocks for the design of various pharmacophoric N-heterocyclic compounds. [1][2][3][4][5][6][7][8][9][10] 2-Azanorbornanes may be considered as conformationally rigid bridged analoges of cyclopentylamine, piperidine, pyrrolidine and exhibit diverse types of biological activity and reactivity. [11,12] Compound 1 (Figure 1) containing an azanorbornene ring exhibits a pronounced antibacterial activity which is higher than for an analog with a piperidine fragment.…”

“…[11,12] Compound 1 (Figure 1) containing an azanorbornene ring exhibits a pronounced antibacterial activity which is higher than for an analog with a piperidine fragment. [8] Other examples of biologically active derivatives of azanorbornanes are compound 2 which exhibits antiviral activity against HPIV-3 and EMCV, [9,13] and structure 3 which is a model of molecule to mimic MEN10627, a constrained cyclic hexapeptide with high affenity for the NK-2 receptor. [14] Authors [14] assumed that the overall dipole moment of MEN10627 would be optimal for binding to the NK-2 receptor.…”

Каркасні Арилсульфонаміди Та Їх Антимікробні Властивості

“…In this regard, the synthesis and chemistry of polycyclic cage-like heterocycles bearing (aza)norbornane and related motifs has attracted considerable attention in recent years both from our group and many others [9][10][11][12][13][14][15][16][17][18][19][20]. As an example, 2-azabicyclo[2.2.1]heptane (azanorbornane) derivatives have also been applied as convenient precursors in the stereoselective synthesis of monocyclic systems useful in medicinal chemistry [8].…”