Synthesis and antimycobacterial activity of disubstituted benzyltriazoles. Smit, F. J, Seldon, R., Aucamp, J., Jordaan, A., Warner, D. F, & N'Da, D. D Medicinal Chemistry Research, 28(12):2279–2293, oct, 2019. ![Synthesis and antimycobacterial activity of disubstituted benzyltriazoles [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex The increasing prevalence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb), the pathogen of human tuberculosis (TB), serves as a strong incentive for the discovery and development of new agents for the treatment of this plight. In search for such drugs, we investigated a series of benzyltriazole derivatives. We herein report the design, synthesis and biological activity of disubstituted benzyltriazoles against the human virulent H37Rv strain of Mtb as well as the toxicity on human embryonic kidney (HEK-293) cells. The derivative 21 featuring trifluoromethyl substituent in para position on the phenyl ring and n-butyl chain in position 4 on the triazole ring was the most active with MIC90 and MIC99 values of 1.73 and 3.2 µM, respectively, in the albumin-free medium. It also displays high selectivity towards bacteria growth inhibition (SI \textgreater 58), thus stands as a better hit for further investigation, including lead optimization, DMPK parameters determination and assessment of its activity in animal models. [Figure not available: see fulltext.].
@article{Smit2019,
abstract = {The increasing prevalence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb), the pathogen of human tuberculosis (TB), serves as a strong incentive for the discovery and development of new agents for the treatment of this plight. In search for such drugs, we investigated a series of benzyltriazole derivatives. We herein report the design, synthesis and biological activity of disubstituted benzyltriazoles against the human virulent H37Rv strain of Mtb as well as the toxicity on human embryonic kidney (HEK-293) cells. The derivative 21 featuring trifluoromethyl substituent in para position on the phenyl ring and n-butyl chain in position 4 on the triazole ring was the most active with MIC90 and MIC99 values of 1.73 and 3.2 µM, respectively, in the albumin-free medium. It also displays high selectivity towards bacteria growth inhibition (SI {\textgreater} 58), thus stands as a better hit for further investigation, including lead optimization, DMPK parameters determination and assessment of its activity in animal models. [Figure not available: see fulltext.].},
author = {Smit, Frans J and Seldon, Ronnett and Aucamp, Janine and Jordaan, Audrey and Warner, Digby F and N'Da, David D},
doi = {10.1007/s00044-019-02458-7},
issn = {15548120},
journal = {Medicinal Chemistry Research},
keywords = {Benzyltriazole,Click chemistry,Drug discovery,TB,Tuberculosis,fund{\_}not{\_}ack,original},
mendeley-tags = {fund{\_}not{\_}ack,original},
month = {oct},
number = {12},
pages = {2279--2293},
title = {{Synthesis and antimycobacterial activity of disubstituted benzyltriazoles}},
url = {https://doi.org/10.1007/s00044-019-02458-7},
volume = {28},
year = {2019}
}
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The derivative 21 featuring trifluoromethyl substituent in para position on the phenyl ring and n-butyl chain in position 4 on the triazole ring was the most active with MIC90 and MIC99 values of 1.73 and 3.2 µM, respectively, in the albumin-free medium. It also displays high selectivity towards bacteria growth inhibition (SI \\textgreater 58), thus stands as a better hit for further investigation, including lead optimization, DMPK parameters determination and assessment of its activity in animal models. 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