Rational design and synthesis of novel dibenzo[b,d]furan-1,2,3-triazole conjugates as potent inhibitors of Mycobacterium tuberculosis

详细信息    查看全文

• 作者：Thirumal Yempala ; Jonnalagadda Padma Sridevi ; Perumal Yogeeswari ; Dharmarajan Sriram ; Srinivas Kantevari
• 关键词：Dibenzofuran ; Mycobacterium tuberculosis ; Click chemistry ; Corey&ndash ; Fuchs reaction ; Cytotoxicity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：7 January, 2014
• 年：2014
• 卷：71
• 期：Complete
• 页码：160-167
• 全文大小：610 K

文摘

A series of novel dibenzo[b,d]furan-1,2,3-triazole conjugates, rationally designed by reorientation of dibenzo[b,d]furan pharmacophore and alkyl/aryl groups appended on 1,2,3-triazole core, were synthesized using click chemistry. The required key intermediate, 2-ethynyl dibenzo[b,d]furan 3 was prepared from dibenzofuran-2-carboxaldehyde using Corey-Fuchs reaction. Further reaction of 3 with various alkyl/aryl azides in the presence of copper catalyst produced 1,2,3-triazole conjugates in excellent yields. Evaluation of all the new compounds for in聽vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294), resulted 5a (MIC: 1.56聽渭g/mL), 5d (MIC: 0.78聽渭g/mL) and 5f (MIC: 0.78聽渭g/mL) as promising lead analogues. Among these three compounds, 1-(4-bromobenzyl)-4-(dibenzo[b,d]furan-2-yl)-1H-1,2,3-triazole (5f) emerged as the most promising antitubercular agent with lowest cytotoxicity (selectivity index: 鈮?5) against the HEK-293T cell line.