N‐([1,1ʹ‐biaryl]‐4‐yl)‐1‐naphthamide‐based scaffolds synthesis, their cheminformatics analyses, and screening as bacterial biofilm inhibitor

Abstract

Naphthamides have pharmacological potential as they express strong activities against microorganisms. The commercially available naphthoyl chloride and 4-bromoaniline were condensed in dry dichloromethane (DCM) in the presence of Et 3 N to form N-(4-bromophenyl)-1-naphthamide (86%) (3). Using a Pd(0) catalyzed Suzuki-Miyaura Cross-Coupling reaction of (3) and various boronic acids, a series of N-([1,1ʹ-biaryl]-4-yl)-1-naphthamide derivatives (4a-h) were synthesized in moderate to good yields. The synthesized derivatives were evaluated for cytotoxicity haemolytic assay and biofilm inhibition activity through in silico and in vitro studies. Molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity risk, and other cheminformatics predict synthesized molecules as biologically active moieties, further validated through in vitro studies in which compounds (4c) and (4f) showed significant haemolytic activity whereas (4e) exhibited an efficient biofilm inhibition activity against Gram-negative bacteria Escherichia coli and Gram-positive bacteria Bacillus subtilis. When forming biofilms, bacteria become resistant to various antimicrobial treatments. Currently, research is focused on the development of agents that inhibit biofilm formation, thus the present work is valuable for preventing future drug resistance.

Facile Synthesis of 5-Bromo-N-Alkylthiophene-2-Sulfonamides and Its Activities Against Clinically Isolated New Delhi Metallo-β-Lactamase Producing Klebsiella pneumoniae ST147

“…Amides simultaneously kill bacteria or cause stagnant growth and have a positive inhibitory impact. 42 …”

Synthesis, Anti-Bacterial and Molecular Docking Studies of Arylated Butyl 2-Bromoisonicotinate Against Clinical Isolates of ESBL-Producing Escherichia coli ST405 and Methicillin-Resistant Staphylococcus aureus

“…At the same time, the amides behave as a hydrophilic binding site against bacterial enzyme proteins, which may cause death or make static growth, leading to good inhibitory activity. 36 Further, we studied the N, O, and S heterocycles carboxamides like N-(4-bromophenyl)furan-2-carboxamide, 32 2-aryl-4-chlorophenyl-5-arylthiophene-2-carboxylates 34 4-bromo-N-(5-methyl-1H-pyrazol-3-yl) benzamide, 35 N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide 37 to study the effectiveness of these scaffolds and found effectiveness against different resistant strains of E. coli, A. baumannii, S. enterica, E. cloacae, S. aureus and K. pneumoniae. We found that heterocyclic carboxamides are pivotal in anti-bacterial activities.…”

Facile Synthesis of Functionalized Phenoxy Quinolines: Antibacterial Activities against ESBL Producing Escherichia coli and MRSA, Docking Studies, and Structural Features Determination through Computational Approach

“…Molecular docking studies were accomplished to identify the stable interactions of synthesized compounds (3b, 3c, 3d, 3e, 3h) against E. coli curli fiber biogenesis biofilm receptor protein using Auto Dock Tools version 1.5.6 (ADT) software [47]. The dataset of compounds was categorized into three activity levels: highly active (3e), moderately active (3c, 3h), and least active (3b, 3d).…”