1. Identification of coumarin - benzimidazole hybrids as potential antibacterial agents: Synthesis, in vitro and in vivo biological assessment, and ADMET prediction.
- Author
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Arya CG, Kishore R, Gupta P, Gondru R, Arockiaraj J, Pasupuleti M, Chandrakanth M, Punya VP, and Banothu J
- Subjects
- Animals, Humans, Mice, Cell Survival drug effects, Dose-Response Relationship, Drug, Gram-Negative Bacteria drug effects, Gram-Positive Bacteria drug effects, Klebsiella pneumoniae drug effects, Molecular Structure, Structure-Activity Relationship, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents chemical synthesis, Benzimidazoles chemistry, Benzimidazoles pharmacology, Benzimidazoles chemical synthesis, Coumarins chemistry, Coumarins pharmacology, Coumarins chemical synthesis, Microbial Sensitivity Tests
- Abstract
The direct-linked coumarin-benzimidazole hybrids, featuring aryl and n-butyl substituents at the N1-position of benzimidazole were synthesized through a Knoevenagel condensation reaction. This reaction involved the condensation of 1,2-diaminobenzene derivatives with coumarin-3-carboxylic acids in the presence of polyphosphoric acid (PPA) at 154 °C. The in vitro antibacterial potency of the hybrid molecules against different gram-positive and gram-negative bacterial strains led to the identification of the hybrids 6m and 6p with a MIC value of 6.25 μg/mL against a gram-negative bacterium, Klebsiella pneumonia ATCC 27736. Cell viability studies on THP-1 cells demonstrated that the compounds 6m and 6p were non-toxic at a concentration of 50 µM. Furthermore, in vivo efficacy studies using a murine neutropenic thigh infection model revealed that both compounds significantly reduced bacterial (Klebsiella pneumonia ATCC 27736) counts (more than 2 log) compared to the control group. Additionally, both compounds exhibited favorable physicochemical properties and drug-likeness characteristics. Consequently, these compounds hold promise as lead candidates for further development of effective antibacterial drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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