2. Academic Validation
  3. Identification of coumarin - benzimidazole hybrids as potential antibacterial agents: Synthesis, in vitro and in vivo biological assessment, and ADMET prediction

Identification of coumarin - benzimidazole hybrids as potential antibacterial agents: Synthesis, in vitro and in vivo biological assessment, and ADMET prediction

  • Bioorg Med Chem Lett. 2024 Sep 15:110:129881. doi: 10.1016/j.bmcl.2024.129881.
C G Arya 1,  Raj Kishore 2,  Pooja Gupta 2,  Ramesh Gondru 3,  Jesu Arockiaraj 4,  Mukesh Pasupuleti 5,  Munugala Chandrakanth 1,  V P Punya 1,  Janardhan Banothu 6
Affiliations

Affiliations

  • 1 Department of Chemistry, National Institute of Technology Calicut, Kozhikode 673601, Kerala, India.
  • 2 Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Sector 10, Janakipuram Extension, Lucknow 226031, Uttar Pradesh, India.
  • 3 Food Chemistry Division, ICMR-National Institute of Nutrition (NIN), Hyderabad 500007, Telangana, India.
  • 4 Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India.
  • 5 Division of Molecular Microbiology & Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Sector 10, Janakipuram Extension, Lucknow 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: mukesh.p@cdri.res.in.
  • 6 Department of Chemistry, National Institute of Technology Calicut, Kozhikode 673601, Kerala, India. Electronic address: janardhan@nitc.ac.in.
PMID: 38996936 DOI: 10.1016/j.bmcl.2024.129881
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.

Keywords

ADMET; Antibacterial activity; Benzimidazole; Coumarin; Hybrids; Klebsiella pneumonia.

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