Selection of orlistat as a potential inhibitor for lipase from Candida species

Infections caused by Candida species manifest in a number of diseases, including candidemia, vulvovaginal candidiasis, endocarditis, and peritonitis. Candida species have been reported to possess lipolytic activity due to the secretion of lipolytic enzymes such as esterases, lipases and phospholipases. Extra-cellular hydrolytic enzymes seem to play an important role in Candida overgrowth. Candidiasis is commonly treated with antimycotics such as clotrimazole and nystatin. The antimycotics bind to a major component of the fungal cell membrane (ergosterol), forming pores that lead to death of the fungus. However, the secondary effects caused during such treatment have aroused a need to develop a treatment based on lipase inhibition. Nonetheless, no such lipase inhibitors for candidiasis treatment are currently available. Thus, we have performed a docking study with the natural inhibitor, orlistat or tetrahydrolipstatin. Our results have shown ten possible binding inhibitors to Candida rugosa lipase (CRL), out of which one possibility was selected, based on the weakest interatomic distance of 2.7 Å. Therefore, we propose the selection and design of a potential inhibitor candidate, orlistat for the treatment of candidiasis infections. However, this study has to be supported with in vitro and in vivo experiments to demonstrate the effectiveness of orlistat in lipase inhibition.