DISCOVERY OF NOVEL SMALL-MOLECULE COMPOUNDS WITH ANTIVIRAL AND ANTICANCER PROPERTIES by Kavya Ramkumar
A Thesis Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (PHARMACEUTICAL SCIENCES) August 2008 Copyright 2008 Kavya Ramkumar
HIV-1 integrase (IN) has emerged as an important therapeutic target for anti-HIV drug development. Its uniqueness to the virus and its critical role in the viral life cycle makes IN suitable for selective inhibition. The recent approval of Raltegravir (MK-0518) has created a surge in interest and great optimism in the field. With an aim to identify novel structural classes with promising IN inhibitory profile, we discovered substituted analogs of 3-acetyl-4-hydroxy-2-pyranones and their difluoridoborate complexes, and 2-thioxo-4-thiazolidinone (rhodanine) derivatives as novel IN inhibitors. We also studied the cytotoxic effects of IN inhibitors and other ellipticine derivatives. In the process, we discovered two novel small-molecules containing chloroacetamide functionality with promising antiproliferative properties.