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Molecules 2018, 23(8), 1945; https://doi.org/10.3390/molecules23081945

Ultrasound Assisted Synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) Benzamide as Challenging Anti-Tubercular Scaffold

1
Maulana Azad P. G. and Research Centre, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad 431001, India
2
Departamento de Química Orgánica, Facultad de Ciencias, Universidad of Santiago de Compostela, Alfonso X el Sabio, 27002 Lugo, Spain
3
Combichem-Bio Resource Centre, Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune 411008, Maharashtra, India
4
Department of Pharmaceutical Chemistry, Srinath College of Pharmacy, Aurangabad 431116, India
5
Department of Pharmaceutical Chemistry, Dr. Rafiq Zakaria Campus, Y. B. Chavan College of Pharmacy, Aurangabad 431001, India
*
Author to whom correspondence should be addressed.
Received: 4 June 2018 / Revised: 13 July 2018 / Accepted: 30 July 2018 / Published: 3 August 2018
(This article belongs to the Special Issue ECSOC-21)
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Abstract

A series of ten novel derivatives of 4-(benzyloxy)-N-(3-chloro-2-(substituted phenyl)-4-oxoazetidin-1-yl) benzamide 6aj were synthesized in good yield from the key compound 4-(benzyloxy)-N′-(substituted benzylidene) benzo hydrazide, called Schiff ’s bases 5aj, by Staudinger reaction ([2 + 2] ketene-imine cycloaddition reaction) with chloro acetyl chloride in the presence of catalyst tri ethylamine and solvent dimethyl formamide (DMF), by using ultra-sonication as one of the green chemistry tools. All the synthesised compounds were evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis (MTB) and most of them showed promising activity with an IC50 value of less than 1 µg/mL. To establish the safety, all the synthesized compounds were further tested for cytotoxicity against the human cancer cell line HeLa and all 6aj compounds were found to be non-cytotoxic in nature. The molecular docking study was carried out with essential enzyme InhA (FabI/ENR) of Mycobacterium responsible for cell wall synthesis which suggests that 6a and 6e are the most active derivatives of the series. The theoretical evaluation of cell permeability based on Lipinski’s rule of five has helped to rationalize the biological results and hence the synthesized azetidinone derivatives 6aj were also analyzed for physicochemical evaluation that is, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and the results showed that all the derivatives could comply with essential features required for a potential lead in the anti-tubercular drug discovery process. View Full-Text
Keywords: green chemistry; ultra-sonication; azetidinone; anti-tubercular screening; cytotoxicity study; molecular docking; ADMET study green chemistry; ultra-sonication; azetidinone; anti-tubercular screening; cytotoxicity study; molecular docking; ADMET study
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Nimbalkar, U.D.; Seijas, J.A.; Borkute, R.; Damale, M.G.; Sangshetti, J.N.; Sarkar, D.; Nikalje, A.P.G. Ultrasound Assisted Synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) Benzamide as Challenging Anti-Tubercular Scaffold. Molecules 2018, 23, 1945.

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