In Silico Screening and Identification of Novel Secondary Metabolites as Effective Anti inflammatory and Anti cancerous Drugs

Abstract

Cancer is a devastating disease, accounting as the second leading cause of death in humans. In recent times chronic inflammation has been closely linked to the cancer development and progression. The lack of selectivity, toxicity and the development of multi-drug resistant cells to the currently available drugs make the successful treatment of cancer difficult. Among the various strategies for cancer treatment, the work carried out in the present thesis pertains to the inhibition of certain selected key enzymatic cancer targets using plant derived secondary metabolites. Plant derived secondary metabolites have been considered to be a safer substitute to synthetic drugs against a number of precarious diseases, including cancer. Thus, for therapeutic applications, identification of specific inhibitors of selected cancer targets coming from natural sources is desirable. Thus, the present work deals with screening and identification of novel secondary metabolites belonging to alkaloids, flavonoids and terpenoids for their inhibitory potential against the selected enzymatic cancer targets, namely cyclooxygenases (COX-1 and COX-2) and 5-lipooxygenase (5-LOX) (as key anti-inflammatory targets), topisomerases (Topo I and Topo IIand#946;) and aromatase (as anti-cancerous targets), using in silico approaches such as pharmacokinetic analyses, homology modeling, molecular docking, dynamic simulation as well as quantitative structure activity relationship (QSAR).he salient findings of the work presented in the thesis are summarized as follows: newline