Reddy K Papi, Bid Hemant K, Nayak V Lakshma, Chaudhary Preeti, Chaturvedi J P, Arya K R, Konwar Rituraj, Narender T
Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattrar Manzil, Lucknow 226 001, Uttar Pradesh, India.
Eur J Med Chem. 2009 Oct;44(10):3947-53. doi: 10.1016/j.ejmech.2009.04.022. Epub 2009 Apr 22.
The taxane diterpneoid 2-deacetoxytaxinine J (2-DAT-J) 1 has been isolated from the bark of Himalayan yew, Taxus baccata L. spp. wallichiana in a reasonably good yield (0.1%) and its anticancer activity against breast cancer cell lines (MCF-7 and MDA-MB-231) and normal human kidney epithelial cell line (HEK-293) has been studied. 2-DAT-J (1) showed significant in vitro activity against breast cancer cell line at a concentration of 20 microM and 10 microM in MCF-7 and MDA-MB-231 respectively. Few novel taxoids were derived (7, 8 and 10-13) from the naturally occurring 2-DAT-J (1) and screened for their anticancer activity. The structure-activity relationship studies indicated that the cinnamoyl group on C-5 and acetyl group on C-10 are essential for the anticancer activity. 2-DAT-J (1) was also tested for its in vivo activity on DMBA-induced mammary tumors in virgin female Sprague Dawley rats at a dose of 10mg/kg body weight orally for 30 days and showed significant regression in mammary tumors as compared to vehicle treated group (p<0.05).
紫杉烷二萜类化合物2-脱乙酰氧基紫杉宁J（2-DAT-J）1已从喜马拉雅红豆杉（Taxus baccata L. spp. wallichiana）的树皮中分离得到，产率相当可观（0.1%），并对其针对乳腺癌细胞系（MCF-7和MDA-MB-231）及正常人肾上皮细胞系（HEK-293）的抗癌活性进行了研究。2-DAT-J（1）在浓度分别为20 microM（针对MCF-7）和10 microM（针对MDA-MB-231）时，对乳腺癌细胞系显示出显著的体外活性。从天然存在的2-DAT-J（1）衍生出了几种新型紫杉烷类化合物（7、8和10 - 13），并对其抗癌活性进行了筛选。构效关系研究表明，C-5位的肉桂酰基和C-10位的乙酰基对于抗癌活性至关重要。还以10mg/kg体重的剂量对未生育的雌性斯普拉格-道利大鼠口服2-DAT-J（1）30天，测试其对二甲基苯并蒽诱导的乳腺肿瘤的体内活性，结果显示与赋形剂处理组相比，乳腺肿瘤有显著消退（p<0.05）。
