Bansal Ranju, Guleria Sheetal, Thota Sridhar, Hartmann Rolf Wolfgang, Zimmer Christina
University Institute of Pharmaceutical Sciences, Sector-14, Panjab University, Chandigarh, India.
Chem Pharm Bull (Tokyo). 2011;59(3):327-31. doi: 10.1248/cpb.59.327.
Taking into consideration the structural requirements for cytotoxicity and aromatase inhibition, several new 16E-arylidenosteroidal derivatives have been prepared and evaluated for their cytotoxic and aromatase inhibitory activity. The new steroidal analogues 3, 5-8 and 11 exhibited significant cytotoxic effects when screened against three cancer cell lines, MCF-7 (breast), NCl-H460 (lung) and SF-268 central nervous system (CNS) at 100 µM and sensible cytotoxic effects subsequently in sixty cancer cell lines derived from nine cancers types (leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate and breast cancers). The imidazolyl substituted steroidal derivatives 5 and 7 exhibited strong inhibition of the aromatase enzyme with 16-[4-{3-(imidazol-1-yl)propoxy}-3-methoxybenzylidene]-5-androstene-3β,17β-diol (7) displaying 13 times more potency in comparison to aminoglutethimide.
考虑到细胞毒性和芳香化酶抑制的结构要求，已制备了几种新型16E-芳叉甾体衍生物，并对其细胞毒性和芳香化酶抑制活性进行了评估。当在100 μM浓度下针对三种癌细胞系MCF-7（乳腺癌）、NCl-H460（肺癌）和SF-268中枢神经系统（CNS）进行筛选时，新型甾体类似物3、5-8和11表现出显著的细胞毒性作用，随后在源自九种癌症类型（白血病、肺癌、结肠癌、中枢神经系统癌、黑色素瘤、卵巢癌、肾癌、前列腺癌和乳腺癌）的60种癌细胞系中也表现出明显的细胞毒性作用。咪唑基取代的甾体衍生物5和7对芳香化酶具有强烈的抑制作用，其中16-[4-{3-(咪唑-1-基)丙氧基}-3-甲氧基苄叉基]-5-雄甾烯-3β,17β-二醇（7）的效力比氨鲁米特高13倍。
