Synthesis and Antibacterial Evaluation of New2‐Phenylbenzimidazole Derivatives

Abstract

Bacterial DNA gyrase and topoisomerase IV are well-characterized targets for both fluoroquinolones (e. g. Ciprofloxacin), which inhibit the catalytic subunits GyrA/ParC, and aminocoumarins (e. g. Novobiocin), which act as GyrB/ParE ATPase inhibitors. Due to the emergence of resistance to the first class, and the safety issues related to the latter, current research is aimed at developing novel synthetic inhibitors for GyrB/ParE in order to overcome the limitations of available drugs. A novel series of benzimidazole derivatives, carrying various functional groups or heterocyclic rings, were synthesized and evaluated for their in vitro antibacterial effect. The majority of the new benzimidazole derivatives showed Gram positive antibacterial activity . Compounds 7 d, 12 a,b and 14 a were selected for the assessment of their binding affinity and enzyme inhibitory activity against the E.coli DNA gyrase and the S. aureus topoisomerase IV. The results revealed good binding as well as dual inhibition against both enzymes. Compounds 7 d (% inhibition 87.71, IC 50 : 0.61 uM) and 14 a (% inhibition: 89.3, IC 50 : 0.58 uM) showed the best results against the E.coli DNA gyrase and the S. aureus topoisomerase IV, respectively. In silico studies revealed a potential good oral absorption of compounds due to compatibility with Lipinski's rule of five. Compound 14 a showed both good druglikeness (3.76) and drug score (0.76) values giving it potential as a promising new drug.[a] O.

Click Synthesis of Novel 3‐(2‐(2,4,5‐Triphenyl‐1H‐imidazol‐1‐yl)ethyl)‐1H‐indoles Catalyzed by Glacial Acetic Acid and their Antibacterial Evaluation

“…A plausible mechanism has been proposed in scheme 2. The mechanism is entirely consistent with previous literatures [42–53] …”

“…The mechanism is entirely consistent with previous literatures. [42][43][44][45][46][47][48][49][50][51][52][53]…”

Novel Para-Aminobenzoic Acid Analogs and Their Potential Therapeutic Applications

“…The results of enzyme inhibitory activity against DNA gyrase (E. coli) and topoisomerase IV (S. aureus) exposed better binding and dual inhibitory activity against both enzymes. The best results were shown by substituted pyrazolidinedione with 89.3% inhibition and an IC 50 value of 0.58 uM against targeted enzymes [81]. The antimicrobial screening suggested three most potent compounds with broad-spectrum activity as compared to standard drug ketoconazole and norfloxacin [57].…”

“…Benzimidazole/thiourea derivatives were achieved by reaction of the preliminary compounds with isothiocyanate and CH 2 Cl 2 [80]. Metal complexes were synthesized by using a refluxing technique [81]. Triazolethiol derivatives were also synthesized in four steps by refluxing PABA in the presence of sulphuric acid to yield aminobenzoate derivatives, which, on further refluxing with hydrazine, yielded hydrazide derivatives.…”