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Design & synthesis of hybrid pharmacophore of β-lactam, 1,8-naphthyridine, and secondary amines; Discover their in vitro antimicrobial, anticancer properties & DFT and ADMET prediction studies

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Abstract

An efficient synthetic strategy was developed for the synthesis of hybrid pharmacophores; encompass the merging of β-lactams, 1,8-naphthyridine and secondary amines/pyridines. With a simple unified synthetic protocol, we prepared a series of substituted 3-chloro-1-((3-(2-(trifluoromethyl)phenyl)-1,8-naphthyridin-2-yl)amino)azetidin-2-one compounds (8a–8j) and evaluated for their antimicrobial, and anticancer activities (against MDA-MB-231 cell line). Notably, compounds 8d, 8g, and 8j were identified as potent anticancer molecules and comparable to Cisplatin. Compounds 8d and 8g were found to have promising antitubercular efficacy even greater than the standards Streptomycin and Ciprofloxacin. Compounds 8a, 8d, 8g, 8i, and 8j also displayed potency against both Gram-positive and Gram-negative bacteria and comparable to Ampicillin & Ciprofloxacin. Further, the biological activities were supported and studied by DFT studies and ADMET predictions.

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Acknowledgements

KMP thanks Dr Benjamin R. Boswell, Department of Chemistry, Stanford University, Stanford, CA, USA for his support in the final corrections of paper. NBP thanks UGC, New Delhi, for the UGC/BSR faculty fellowship.

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Authors and Affiliations

  1. Department of Chemistry, Veer Narmad South Gujarat University, Surat, 395007, Gujarat, India

    Keyur M. Pandya & Navin B. Patel

  2. Department of Humanities and Sciences, CVR College of Engineering, Hyderabad, 501510, India

    Satyanarayana Battula

  3. Department of Chemistry, Sri Venkateshwara College of Engineering & Technology, Etcherla, Srikakulam, Andhra Pradesh, India

    K. A. Aravinda Kumar

  4. Shri A. N. Patel P. G. Institute of Science and Research, Sardar Patel University, V. V. Nagar, Gujarat, India

    Rajesh J. Patel

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  1. Keyur M. Pandya
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Pandya, K.M., Battula, S., Kumar, K.A.A. et al. Design & synthesis of hybrid pharmacophore of β-lactam, 1,8-naphthyridine, and secondary amines; Discover their in vitro antimicrobial, anticancer properties & DFT and ADMET prediction studies. Med Chem Res 32, 1098–1108 (2023). https://doi.org/10.1007/s00044-023-03058-2

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