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Design, synthesis, molecular docking, and dynamic studies of novel thiazole derivatives incorporating benzimidazole moiety and assessment as antibacterial agents

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Abstract

A general and sustainable approach for the synthesis of benzimidazole-thiazole compounds via an efficient, one-pot, domino, pseudo-four-component reaction using 5-amino-2-mercaptobenzimidazole, aralkyl halides, ammonium thiocyanate, and substituted α-bromo-acetophenones in glacial acetic acid at ambient temperature to give final compounds (4a–p) in good yields in shorter time. The spectral data of synthesized compounds were evaluated by analytical and spectral techniques (IR, 1H-NMR, 13C-NMR, and ESI-HRMS). Further, some of the synthesized compounds were screened for their in-vitro antibacterial activity studies using the agar well diffusion method against Gram-positive Streptococcus pneumoniae (2451) bacteria and Gram-negative Proteous mirabilis (2081) bacteria. Based on the MIC results, it was observed that the most active compounds 4b, 4e, 4f, and 4k show promising antibacterial activity with the zone of inhibition values of 2.85 cm 2.75 cm, 3.6 cm, and 3.3 cm against both Gram-negative and positive bacteria cell lines, respectively. Further, we have also insight into the molecular simulation studies, based on the binding results, compound 4i showed stable binding interactions with streptomycin drug with the active site of the gyrase protein (PDB ID: 1KIJ). The structure–activity relationship (SAR) studies of all the title scaffolds were also established. The antibacterial activity, molecular docking studies, and molecular dynamic simulations of the title compounds suggested that these are promising antibacterial active skeletons.

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Acknowledgements

The authors are thankful to the Director of the National Institute of Technology, Warangal Telangana, India, for providing lab facilities, and one of the authors R.C. thankful to the Ministry of Education, Government of India, for providing a research fellowship. R. C. wishes to thank Dr. Amrutha V Audipudi for biological activity and computational calculations.

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Authors and Affiliations

  1. Department of Chemistry, National Institute of Technology, Warangal, Telangana, 506004, India

    Raju Chedupaka, Akanksha Ashok Sangolkar, Srikanth Mamidala, Papisetti Venkatesham, Santhosh Penta & Rajeswar Rao Vedula

  2. Department of Botany and Microbiology, Acharya Nagarjuna University, Guntur, A.P., 522510, India

    Amrutha V. Audipudi

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  1. Raju Chedupaka
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Contributions

Raju Chedupaka carried out the laboratory work, conceptualization, wrote the main manuscript text, and methodology. Amrutha V Audipudi did the work on biology part of the manuscript. Akanksha Ashok Sangolkar did the computational part of the manuscript. Srikanth Mamidala helped in reviewing, editing, and formal analysis of the manuscript. Papisetti Venkatesham and Santhosh Penta helped for validation. Rajeswar Rao Vedula was the supervisor of the research work.

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Correspondence to Rajeswar Rao Vedula.

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Chedupaka, R., Audipudi, A.V., Sangolkar, A.A. et al. Design, synthesis, molecular docking, and dynamic studies of novel thiazole derivatives incorporating benzimidazole moiety and assessment as antibacterial agents. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10675-x

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