Molecular modeling of the interaction of novel hydroxy- and aminobisphosphonate...

• Author(s): Duarte, Luís F. ; Teixeira, Fátima C. ; Fausto, Rui
• Date: 2010
• Persistent ID: http://hdl.handle.net/10316/17972
• Origin: Estudo Geral - Universidade de Coimbra
• Subject(s): Bisphosphonates; Hydroxyapatite binding; Molecular modeling; Molecular mechanics
• Document Type: Article
• Language: English

Description

Bisphosphonates (BPs) are a class of drugs widely used in the treatment of several metabolic bone disorders associated with increased bone resorption. Although BPs can directly inhibit the cellular activity of osteoclasts, their ability to adsorb on bone mineral is also an important factor in determining their potency and duration of action. In this study, we performed a molecular mechanics analysis of the molecular structures of 18 novel hydroxy- and aminobisphosphonates and examined their interactions with hydroxyapatite. From the calculated interaction energies, general rules were extracted relating structural characteristics of BPs and their affinities to the mineral. The results obtained were shown to be in agreement with in vitro and in vivo studies performed for some of the studied BPs. Keywords: Bisphosphonates, hydroxyapatite binding, molecular modeling, molecular mechanics This paper is dedicated to Prof. António M. d’A. Rocha Gonçalves. In his classes of organic chemistry, at the University of Coimbra, he was the first to show me the beauty of structural chemistry (R.F.)