Synthesis, evaluation and 3D QSAR analysis of novel estradiol-RGD octapeptide conjugates with oral anti-osteoporosis activity.

Abstract:

: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-osteoporosis activity was significantly higher than that of estradiol and estradiol-RGD tetrapeptide conjugates, and their risks of thrombogenesis and endometrial hyperplasia were significantly lower than that of estradiol and 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 r(2) of the 3D QSAR equations up to 0.995 and 0.988 indicates that they are capable of predicting a comparatively exact anti-osteoporosis activity for a conjugate.

journal_name

Eur J Med Chem

authors

Liu J,Zhang X,Zhao M,Peng S

doi

10.1016/j.ejmech.2008.09.036

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

1689-704

issue

4

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(08)00433-9

journal_volume

44

pub_type

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