European Journal of Medicinal Chemistry 2010-11-01

Analysis of physico-chemical properties of substrates of ABC and MFS multidrug transporters of pathogenic Candida albicans.

Nidhi Puri, Om Prakash, Raman Manoharlal, Monika Sharma, Indira Ghosh, Rajendra Prasad

Index: Eur. J. Med. Chem. 45 , 4813-26, (2010)

Full Text: HTML

Abstract

In this study, we have explored the structure activity relationships of substrates of two major, promiscuous, multidrug transporters of an opportunistic human pathogen Candida albicans namely, CaCdr1p and CaMdr1p. To differentiate between substrates and non-substrates, the susceptibilities of the Saccharomyces cerevisiae strains over-expressing CaCdr1p or CaMdr1p were determined for 67 structurally diverse xenobiotics. A comparison of physico-chemical indices of these tested compounds enabled identification of molecular descriptors such as, degree of hydrophobicity (MLogP), geometrical descriptor (DISPv), molecular edge descriptor (MDEC.12 and MDEC.13) and 3D-Morse descriptors, that allowed their segregation into substrates and non-substrates for both the transporter proteins. Taken together, present study provides first evidence of chemical basis of substrate specificities of two clinically relevant multidrug transporters of an opportunistic human pathogen C. albicans.Copyright © 2010 Elsevier Masson SAS. All rights reserved.