Synthesis, evaluation and 3D QSAR analysis of novel estradiol-RGD octapeptide conjugates with oral anti-osteoporosis activity
To enhance the potency, reduce the side effects and improve oral property of estradiol in estrogen replacement therapy (ERT), 6 novel estradiol-RGD octapeptide conjugates have been prepared. In an ovariectomized mouse osteoporotic model, at an oral dosage of 110.3 nmol/kg per day, their anti-oste oporosis activity was evaluated, and the results showed significantly higher oral anti-osteoporosis potency and lower risks of thrombogenesis and endometrial hyperplasia than those of estradiol and 6 estradiol-RGD tetrapeptide conjugates. Using QSAR module of Cerius2. the 3D QSAR was performed for both femur weights and femur ash weights of estradiol-RGD peptide conjugates receiving mice. The r2 of the 3D QSAR equations up to 0.995 and 0.988 indicates that they are capable of predicting a compara tively exact anti-osteoporosis activity for a conjugate.
Estradiol RCD octapeptide Conjugate Anti-osteoporosis 3D QSAR
Jiangyuan Liu Xiaoyi Zhang Ming Zhao Shiqi Peng
College of Pharmaceutical Sciences.Peking University, Beijing 100083.PR China College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069.PR China College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069.PR China Correspondin College of Pharmaceutical Sciences.Peking University, Beijing 100083.PR China College of Pharmaceuti
国际会议
广州
英文
298-313
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）