DEVELOPMENT OF NOVEL TOPOISOMERASE II INHIBITORS

Abstract

The World Health Organization (WHO) considers tuberculosis to be the most dangerous chronic communicable disease in the world, infecting two billion people or one-third of the world’s population. Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a leading cause of mortality worldwide into 21st century. Tuberculosis is second only to AIDS among other infectious diseases in causing deaths worldwide. The emergence of AIDS, decline of socioeconomic standards and a reduced emphasis on tuberculosis control programmer contribute to the disease’s resurgence in industrialized countries. In last decade treatment of infectious disease had undergone a productive shift. An advancement in the immunization, biotechnology and immunization novel techniques had been developed for delivering diverse biologicals. In this study we selected computational approaches to design a library of compounds based on medicinal chemistry approaches. We evaluated a series of organic compounds for their binding studies against selected targets. The target selected for this study was topoisomerase II a potential target in the antitubercular therapy. The topoisomerase II was selected for screening of the compounds against structure based model using the co-crystal structure reported in PDB database. The in-silico designed library of 200 was further evaluated for their docking scores and the top scored compounds from this library were used for the development of potential lead candidates for the selected target. These potential leads top 20 were further simplified using the rational medicinal chemistry approaches to minimize their synthetic cost.