Synthesis and molecular docking study of pyrazole clubbed oxazole as antibacterial agents
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Synthesis and molecular docking study of pyrazole clubbed oxazole as antibacterial agents Nisheeth C. Desai1 · Darshita V. Vaja1 · Surbhi B. Joshi1 · Vijay M. Khedkar2 Received: 20 July 2020 / Accepted: 26 September 2020 © Springer Nature B.V. 2020
Abstract We have developed a simple synthetic protocol for the preparation of novel 3-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-arylisoxazoles. The structure of synthesized compounds was elucidated by spectral techniques like FT-IR, 1HNMR, 13C-NMR, and mass. The novel bioactive compounds 3a-t were evaluated for in vitro antibacterial activity on several bacterial species. Compounds 3c (–4–NO2), 3o (–4–F), and 3r (–3,4–Cl2) exhibited good in vitro antibacterial activity. Furthermore, molecular docking on DNA gyrase subunit b could shed some light on the mechanism of action which can serve as a guide for lead optimization.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116 4-020-04286-6) contains supplementary material, which is available to authorized users. * Nisheeth C. Desai [email protected] 1
Division of Medicinal Chemistry, Department of Chemistry (DST‑FIST Sponsored & UGC NON‑SAP), Maharaja Krishnakumarsinhji Bhavnagar University, Mahatma Gandhi Campus, Bhavnagar 364002, India
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Department of Pharmaceutical Chemistry, School of Pharmacy, Vishwakarma University, Pune, Maharashtra 411 048, India
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Graphic abstract
Keywords Pyrazole · Isoxazole · Antibacterial activity · Molecular modelling · Docking
Introduction The inactivation of antibiotics because of the resistance towards the existing antimicrobial agents is one of the major challenges posed to the scientific community. The mortality and morbidity data, published by WHO, support this fact. Antibiotic resistance is now a growing threat to mankind [1]. Chemists are trying to find the solution to this problem [2, 3]. To find a solution to this pressing problem, our research group has extensively synthesized antimicrobial scaffolds with a novel mechanism of action against these pathogens [4–7]. Azoles are known for their antibacterial property. Selma SARAÇ and several other workers have synthesized and developed azole-based antimicrobial compounds that showed good-to-excellent activity [8–12]. In continuation, we have incorporated pyrazole and isoxazole as a building block of our targeted compounds and studied their antibacterial efficiency. Synthesis of isoxazoles goes back to 1883 when it was explained by Claisen in 1888 [13] utilising β-diketones and hydroxylamine. It ultimately gave 3,5-disubstituted isoxazoles. However, the formation of unsymmetrical 1,3-diketones can result in
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Synthesis and molecular docking study of pyrazole clubbed…
mixtures of isomeric isoxazoles. Numerous research groups have developed isoxazoles through 1,3-dipolar cycloaddition or 3 + 2 cycloaddition. The major disadvantages of this method are low yield, side reactions, and poor regioselectivity [14]. Wit
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