Click chemistry inspired facile synthesis and bioevaluation of novel triazolyl analogs of Ludartin

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• 作者：Shabir H. Lone ; Khursheed A. Bhat ; Rabiya Majeed ; Abid Hamid ; Mohd A. Khuroo
• 关键词：Ludartin ; Michael-addition ; Huisgen 1 ; 3-dipolar cycloaddition ; Cytotoxicity
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 February, 2014
• 年：2014
• 卷：24
• 期：4
• 页码：1047-1051
• 全文大小：1807 K

文摘

A convenient and modular synthesis involving diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction was carried out to furnish 1,4-disubstituted-1,2,3-triazoles of Ludartin. This reaction scheme involving Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction leading to the formation of triazolyl analogs is being reported for the first time. All the triazolyl products were characterised using spectral data analysis. Sulphorhodamine B cytotoxicity screening of the resulting products against a panel of five human cancerous cell-lines revealed that few of the analogs display promising broad spectrum cytotoxic effect. Among all the synthesized compounds, only 3q displayed the best cytotoxic effect with IC₅₀ values of 12, 11, 38, 39 and 8.5 渭M but less than the standard Ludartin (1) with IC₅₀ values of 6.3, 7.4, 7.5, 6.9 and 0.5 渭M against human neuroblastoma (T98G), lung (A-549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell lines, respectively. The present synthesis was designed based on the previous literature reports of Ludartin as an aromatase inhibitor. Our work provides an initial study on structure-activity relationship of triazolyl analogs of sesquiterpene lactones in general and Ludartin (1) in particular.