Arylquinolinecarboxamides: synthesis, in vitro and in silico studies against Mycobacterium tuberculosis

Arylquinolinecarboxamides: synthesis, in vitro and in silico studies against Mycobacterium tuberculosis. Bokosi, F. R B, Beteck, R. M, Jordaan, A., Seldon, R., Warner, D. F, Tshiwawa, T., Lobb, K., & Khanye, S. D Journal of Heterocyclic Chemistry, 58(11):2140–2151, John Wiley & Sons, Ltd, jul, 2021.

Paper doi abstract bibtex

A series of fourteen 6-substituted-2-(methoxyquinolin-3-yl) methyl)-N-(pyridin- 3-ylmethyl) benzamides was prepared from commercially available anilines in five simple and convenient synthetic steps. The structures of all new products were confirmed by routine spectroscopic methods: IR, 1Hand 13CNMR, and HRMS (electrospray ionization). The resulting arylquinolinecarboxamides were subjected to biological screening assay for in vitro inhibitory activity against Myco- bacterium tuberculosis (Mtb) H37Rv strain. Several compounds exhibited modest antitubercular activity with compounds 8–11, 15 and 19 exhibiting MIC90 values in the range of 32–85 $μ$M. The antitubercular data suggested that inhibition of Mtb can be imparted by the introduction of a non-polar substituent on C-6 of the quinoline scaffold. Further, to understand the possiblemodeofactionofthe series, the reported compounds and bedaquiline were subjected to in silico dock- ing studies against MtbATPase to determine their potential to interfere with the mycobacterial adenosine triphosphate (ATP) synthase. The results showed that these compounds have the potential to serve as antimycobacterial agents. In silico ADME pharmacokinetic prediction results showed the ability of these arylquinolinecarcboxamides to be absorbed, distributed, metabolized and excreted efficiently.

@article{Bokosi2021,
abstract = {A series of fourteen 6-substituted-2-(methoxyquinolin-3-yl) methyl)-N-(pyridin- 3-ylmethyl) benzamides was prepared from commercially available anilines in five simple and convenient synthetic steps. The structures of all new products were confirmed by routine spectroscopic methods: IR, 1Hand 13CNMR, and HRMS (electrospray ionization). The resulting arylquinolinecarboxamides were subjected to biological screening assay for in vitro inhibitory activity against Myco- bacterium tuberculosis (Mtb) H37Rv strain. Several compounds exhibited modest antitubercular activity with compounds 8–11, 15 and 19 exhibiting MIC90 values in the range of 32–85 $\mu$M. The antitubercular data suggested that inhibition of Mtb can be imparted by the introduction of a non-polar substituent on C-6 of the quinoline scaffold. Further, to understand the possiblemodeofactionofthe series, the reported compounds and bedaquiline were subjected to in silico dock- ing studies against MtbATPase to determine their potential to interfere with the mycobacterial adenosine triphosphate (ATP) synthase. The results showed that these compounds have the potential to serve as antimycobacterial agents. In silico ADME pharmacokinetic prediction results showed the ability of these arylquinolinecarcboxamides to be absorbed, distributed, metabolized and excreted efficiently.},
author = {Bokosi, Fostino R B and Beteck, Richard M and Jordaan, Audrey and Seldon, Ronnet and Warner, Digby F and Tshiwawa, Tendamudzimu and Lobb, Kevin and Khanye, Setshaba D},
doi = {10.1002/JHET.4340},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Bokosi et al. - 2021 - Arylquinolinecarboxamides synthesis, in vitro and in silico studies against iMycobacterium tuberculosisi.pdf:pdf},
issn = {1943-5193},
journal = {Journal of Heterocyclic Chemistry},
keywords = {MtbATPase,Mycobacterium tuberculosis,antitubercular,arylquinolinecarboxamides,fund{\_}not{\_}ack,original},
mendeley-tags = {fund{\_}not{\_}ack,original},
month = {jul},
number = {11},
pages = {2140--2151},
publisher = {John Wiley {\&} Sons, Ltd},
title = {{Arylquinolinecarboxamides: synthesis, in vitro and in silico studies against \textit{Mycobacterium tuberculosis}}},
url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jhet.4340 https://onlinelibrary.wiley.com/doi/abs/10.1002/jhet.4340 https://onlinelibrary.wiley.com/doi/10.1002/jhet.4340},
volume = {58},
year = {2021}
}

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