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Novel heterocyclic 1,3,4-oxadiazole derivatives of fluoroquinolones as a potent antibacterial agent: Synthesis and computational molecular modeling

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Abstract

Design and synthesis of novel series of 1,3,4-oxadiazoles containing FQs derivatives and screened their antibacterial, antimycobacterial properties. The synthesized compounds were characterized by different spectral techniques like IR, 1H NMR, 13C NMR, mass and elemental analysis. The results of the antimicrobial activity and compounds 6d, 6b, 6e, 6f and 6a demonstrated potent antibacterial activities with zone of inhibition of 42, 36, 37, 34 and 30 mm against S. aureus, E. faecalis, S. pneumoniae, E. coli and K. pneumoniae, respectively. 1,3,4-Oxadiazole derivatives 6a, 6b, 6 g were showed excellent antimycobacterial activity against M. smegmatis H37Rv with MICs 22.35, 16.20, 20.28 µg/mL, respectively. FQs 6d and 6b exhibited highest hydrogen bonding interactions with Asp83 (3.11 A˚), Ser80 (2.15 A˚) Asp27 (σ-σ), Arg87 (Π-Π), Arg87 (Π-Π), Ser80 (σ-σ), Ala84 (σ-σ) and binding energies ΔG =  − 6.41, − 6.97 kcal/mol with active site of topoisomerase-IV from S. pneumoniae [4KPE]. We performed a computational investigation of compounds 6a–j for their absorption, distribution, metabolism and excretion (ADME) properties by using the Molinspiration, Molsoft toolkits. The ligands 6f, 6d and 6b reveal the highest pharmacokinetic properties and possess maximum drug-likeness model score 1.59, 1.46 and 1.23, respectively.

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Abbreviations

PSA:

Polar surface area

LGA :

Lamarckian genetic algorithm

NRL :

Nuclear receptor legend

ICM :

 Ion channel modulator

ADME :

 Absorption, distribution, metabolism and excretion

MIC :

Minimum inhibitory concentration

PDBQT:

 Protein data bank includes partial charges ('Q') and atom types ('T')

ADT:

 Autodock tools

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Acknowledgements

ATR is thankful to CCST, IST, JNTUH University, Hyderabad, for providing laboratory and other facilities.

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Authors and Affiliations

  1. Centre for Chemical Sciences and Technology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad, Telangana, 500085, India

    Tejeswara Rao Allaka, Bhaskar Kummari, Naveen Polkam, Naveen Kuntala & Jaya Shree Anireddy

  2. Centre for Biotechnology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad, Telangana, 500085, India

    Kalyani Chepuri

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  1. Tejeswara Rao Allaka
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  2. Bhaskar Kummari
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Allaka, T.R., Kummari, B., Polkam, N. et al. Novel heterocyclic 1,3,4-oxadiazole derivatives of fluoroquinolones as a potent antibacterial agent: Synthesis and computational molecular modeling. Mol Divers 26, 1581–1596 (2022). https://doi.org/10.1007/s11030-021-10287-3

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