Design, synthesis and biological evaluation of novel 1,2,3-triazolyl \(\upbeta \) -hydroxy alkyl/carbazole hybrid molecules
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- 作者：Mohammad Navid Soltani Rad ; Somayeh Behrouz ; Marzieh Behrouz…
- 刊名：Molecular Diversity
- 出版年：2016
- 出版时间：August 2016
- 年：2016
- 卷：20
- 期：3
- 页码：705-718
- 全文大小：1,144 KB
- 刊物类别：Chemistry and Materials Science
- 刊物主题：Chemistry
Analytical Chemistry
Polymer Sciences
Organic Chemistry
Pharmacy - 出版者：Springer Netherlands
- ISSN：1573-501X
- 卷排序：20
文摘
The design, synthesis and biological study of several novel 1,2,3-triazolyl \(\upbeta \)-hydroxy alkyl/carbazole hybrid molecules as a new type of antifungal agent has been described. In this synthesis, the N-alkylation reaction of carbazol-9-ide potassium salt with 3-bromoprop-1-yne afforded 9-(prop-2-ynyl)-9H-carbazole. The ‘Click’ Huisgen cycloaddition reaction of 9-(prop-2-ynyl)-9H-carbazole with diverse \(\upbeta \)-azido alcohols in the presence of copper-doped silica cuprous sulphate led to target molecules in excellent yields. The in vitro antifungal and antibacterial activities of title compounds were screened against various pathogenic fungal strains, Gram-positive and/or Gram-negative bacteria. In particular, 1-(4-((9H-carbazol-9-yl) methyl)-1H-1,2,3-triazol-1-yl)-3-butoxypropan-2-ol (10e) proved to have potent antifungal activity against all fungal tests compared with fluconazole and clotrimazole as studied reference drugs. Our molecular docking analysis revealed an appropriate fitting and a potential powerful interaction between compound 10e and an active site of the Mycobacterium P450DM enzyme. The strong hydrogen bondings between \(\upbeta \)-hydroxyl and ether groups in 10e were found to be the main factors that drive the molecule to fit in the active site of enzyme. The in silico pharmacokinetic studies were used for a better description of 10a–10n as potential lead antifungal agents for future investigations.KeywordsAntifungalAntibacterialCarbazole\(\upbeta \)-Hydroxy 1, 2, 3-triazoleMycobacterium P450DM