Multi-target drug discovery in anti-cancer therapy: Fragment-based approach toward the design of potent and versatile anti-prostate cancer agents

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Alejandro Speck Planche (Author) Other; Valeria V Kleandrova (Author) Other; Feng Luan (Author) Other; Natalia N D S Cordeiro (Author) FCUP

Journal

Title: Bioorganic and Medicinal Chemistry

Vol. 19

Pages: 6239-6244

ISSN: 0968-0896

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 71 Citations

Scopus - 72 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-002-K62

DOI: 10.1016/j.bmc.2011.09.015

Abstract (EN): Prostate cancer (PCa) is the second-leading cause of cancer deaths among men in the around the world. Understanding the biology of PCa is essential to the development of novel therapeutic strategies, in order to prevent this disease. However, after PCa make metastases, chemotherapy plays an extremely important role. With the pass of the time, PCa cell lines become resistant to the current anti-PCa drugs. For this reason, there is a necessity to develop new anti-PCa agents with the ability to be active against several PCa cell lines. The present work is an effort to overcome this problem. We introduce here the first multi-target approach for the design and prediction of anti-PCa agents against several cell lines. Here, a fragment-based QSAR model was developed. The model had a sensitivity of 88.36% and specificity 89.81% in training series. Also, the model showed 94.06% and 92.92% for sensitivity and specificity, respectively. Some fragments were extracted from the molecules and their contributions to anti-PCa activity were calculated. Several fragments were identified as potential substructural features responsible of anti-PCa activity and new molecular entities designed from fragments with positive contributions were suggested as possible anti-PCa agents.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6