Synthesis and bioactive evaluations of novel benzotriazole compounds as potential antimicrobial agents and the interaction with calf thymus DNA

Abstract

A novel series of benzotriazole derivatives were synthesized and characterized by NMR, IR and MS spectra. The bioactive assay manifested that most of the new compounds exhibited moderate to good antibacterial and antifungal activities against the tested strains in comparison to reference drugs chloromycin, norfloxacin and fluconazole. Especially, 2,4-dichlorophenyl substituted benzotriazole derivative 6f displayed good antibacterial activity against MRSA with MIC value of 4 μg/mL, which was 2-fold more potent than Chloromycin, and it also displayed 3-fold stronger antifungal activity (MIC = 4 μg/mL) than fluconazole (MIC = 16 μg/mL) against Beer yeast. The preliminary interactive investigations of compound 6f with calf thymus DNA revealed that compound 6f could effectively intercalate into DNA to form compound 6f-DNA complex which might block DNA replication to exert antimicrobial activities. Molecular docking experiments suggested that compound 6f projected into base-pairs of DNA hexamer duplex forming two hydrogen bonds with guanine of DNA. The theoretical calculations were in accordance with the experimental results.

Design, Synthesis, Antimicrobial Evaluation of Novel 2‐Oxo‐4‐Substituted Aryl‐Azetidine Benzotriazole Derivatives**

“…A variety of pharmacophore of benzotriazole was hybridized form used against microbial inhibitory action such as Schiff bases [14] furan moiety, azole derivatives, isatin derivatives, carnothionamide moiety etc [15–16] . A novel compound azetidine‐2‐one [17,18] created this cyclic amide by H. Staudinger in two different azetidinones in 1907, those containing β‐lactam ring. Many broad spectrum β ‐lactam antibiotics are present in market, including penicillin, cephalosporins, clavulanic acid, sulbactum, tazobactum and nocardicin containing azetidine‐2‐one [19] .…”

Design, Synthesis, and Antipoliferative Activities of Novel Substituted Imidazole-Thione Linked Benzotriazole Derivatives

“…Benzotriazole-based compounds are unique nitrogen-containing heterocycles that have attracted significant attention from medicinal chemists as a promising class of bioactive heterocyclic products that exhibit numerous biological properties, such as anticancer [ 27 , 28 , 29 , 30 , 31 ] (BZI, Figure 1 ), antibacterial [ 32 , 33 ], antiviral [ 34 , 35 ], and anti-inflammatory activities [ 36 , 37 ]. Furthermore, substitution of the 3,4,5-trimethoxyphenyl ring of isoCA-4 by a quinazoline nucleus [ 38 ] or quinoline [ 39 , 40 , 41 ] led to tubulin inhibitor with potent antiproliferative deeds versus a variety of cancerous cell lines.…”