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首页> 外文期刊>RSC Advances >1,2,3-Triazole–quinazolin-4(3H)-one conjugates: evolution of ergosterol inhibitor as anticandidal agent
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1,2,3-Triazole–quinazolin-4(3H)-one conjugates: evolution of ergosterol inhibitor as anticandidal agent

机译：1,2,3-三唑-喹唑啉-4（3H）-一个结合物：麦角固醇抑制剂作为抗候选试剂的演变

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The present study describes the synthesis of 1,2,3-triazole–quinazolinone conjugates ( 5a–q ) from ethyl 4-oxo-3-(prop-2-ynyl)-3,4-dihydroquinazoline-2-carboxylate and phenyl azide/substituted phenyl azides employing Cu( I ) catalysed Huisgen 1,3-dipolar cycloaddition. The corresponding acids ( 6a–q ) were obtained by hydrolysis of esters ( 5a–q ) to study the effect of these functionalities on the biological activity. All synthesized compounds were screened for in vitro anticandidal evaluation against Candia albicans , Candida glabrata and Candida tropicalis strains. The results indicated that compound 5n showed potent anticandidal activity with IC _(50) in the range of 8.4 to 14.6 μg mL ~(?1) . Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed the non-toxic nature of the selected compounds. Growth kinetic study with compound 5n showed its fungicidal nature as no significant growth of Candida cells was observed even after 24 h. Cellular ergosterol content was determined in the presence of different concentrations of 5n to measure the activity of lanosterol 14α-demethylase indirectly. The results showed significant disruption of the ergosterol biosynthetic pathway through inhibition of lanosterol 14α-demethylase activity supported by docking studies (PDB: 5v5z). Overall, this study demonstrates the anticandidal potential of 5n which can serve as the lead for further structural optimization and SAR studies.
机译：本研究描述了由4-氧代-3-（丙-2-炔基）-3,4-二氢喹唑啉-2-羧酸乙酯和叠氮化苯合成1,2,3-三唑-喹唑啉酮共轭物（5a-q）使用Cu（I）的α-取代的苯基叠氮化物催化Huisgen 1,3-偶极环加成。相应的酸（6a–q）是通过酯（5a–q）的水解获得的，以研究这些功能对生物活性的影响。筛选所有合成的化合物，以针对白色念珠菌，光滑念珠菌和热带念珠菌菌株进行体外抗候选评价。结果表明，化合物5n显示出有效的抗候选活性，IC _（50）范围为8.4至14.6μgmL〜（？1）。使用人红细胞（hRBCs）的溶血活性和对人胚胎肾（HEK-293）细胞进行MTT分析的细胞毒性揭示了所选化合物的无毒性质。化合物5n的生长动力学研究表明其杀真菌性质，因为即使在24小时后也未观察到念珠菌细胞的显着生长。在不同浓度的5n存在下测定细胞中麦角固醇的含量，以间接测量羊毛甾醇14α-脱甲基酶的活性。结果显示，对接研究支持通过抑制羊毛甾醇14α-脱甲基酶活性来显着破坏麦角甾醇的生物合成途径（PDB：5v5z）。总的来说，这项研究证明了5n的抗候选潜力，可以作为进一步结构优化和SAR研究的线索。

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