Ultrasound Assisted Synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) Benzamide as Challenging Anti-Tubercular Scaffold
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Título: | Ultrasound Assisted Synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) Benzamide as Challenging Anti-Tubercular Scaffold |
Autor/a: | Nimbalkar, Urja D. Seijas Vázquez, Julio Antonio Borkute, Rachna Damale, Manoj G. Sangshetti, Jaiprakash N. Sarkar, Dhiman Nikalje, Anna Pratima G. |
Centro/Departamento: | Universidade de Santiago de Compostela. Departamento de Química Orgánica |
Palabras chave: | Green chemistry | Ultra-sonication | Azetidinone | Anti-tubercular screening | Cytotoxicity study | Molecular docking | ADMET study | |
Data: | 2018 |
Editor: | MDPI |
Cita bibliográfica: | 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 |
Resumo: | A series of ten novel derivatives of 4-(benzyloxy)-N-(3-chloro-2-(substituted phenyl)-4-oxoazetidin-1-yl) benzamide 6a–j were synthesized in good yield from the key compound 4-(benzyloxy)-N′-(substituted benzylidene) benzo hydrazide, called Schiff ’s bases 5a–j, 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 6a–j 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 6a–j 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 |
Versión do editor: | https://doi.org/10.3390/molecules23081945 |
URI: | http://hdl.handle.net/10347/22329 |
DOI: | 10.3390/molecules23081945 |
E-ISSN: | 1420-3049 |
Dereitos: | © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/) |
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