4. Molecular modelling analysis of the metabolism of sulindac

Fazlul Huq

School of Biomedical Sciences, Faculty of Health Sciences, The University of Sydney, Australia. f.huq@fhs.usyd.edu.au

(Received  05 December 2005; accepted 21 February 2006)

Abstract: Sulindac (SD) is a non-steroidal anti-inflammatory drug that is also a promising chemopreventive agent against colorectal cancer (CRC) which is one of the most common causes of cancer death in the United states and other Western countries. In vivo, SD is converted to suldinac sulfide (SS) and suldinac sulfone (SSN). SD, SS and SSN besides having effect on the inflammatory-relevant cyclooxygenase (COX) pathway such as apoptosis-inducing pathway, cause antiproliferative effects independent of COX inhibition. Molecular modelling analyses using the molecular modelling program Spartan ’02 show that SD, SS and SSN are kinetically labile that renders them capacity to deactivate ROS and RNS. The ROS and RNS scavenging activity of SD and its metabolites may contribute strongly to their anti-inflammatory and anticarcinogenic efficacy.

Keywords: Sulindac, anti-inflammatory drug, colorectal cancer, antioxidant, molecular modelling

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