Discovery and Development of Novel Prototype Antibiotics for Opportunistic Infections Related to Acquired Immunodeficiency Syndrome

Abstract

The major AIDS-related opportunistic fungal and bacterial infections are candidiasis, cryptococcosis and mycobacteriosis. The need for new, more effective and less toxic antibiotics for the treatment of these infections is obvious in light of the significant toxicities and failure rates of the currently available agents. In the past, the discovery of new antibiotics has relied primarily on the isolation of such agents from natural sources. The major advantage of this approach is the likelihood of identifying new prototype drugs with different chemical structures, and hence, possible new mechanisms and less likelihood of similar toxicities and cross-resistance. Although in the past microorganisms have been the primary source of new antibiotics, higher plants are now recognized as important sources of new antimicrobial agents. Recent efforts to discover new prototype antibiotics with potential utility specifically for the treatment of opportunistic disseminated mycoses and mycobacteriosis are discussed. Initial in vitro evaluation of higher plant extracts for antifungal and antimycobacterial activity is followed by fractionation and purification of active extracts using a bioassay-directed scheme. Pure compounds with significant in vitro activity are evaluated for in vivo efficacy in established animal models of disseminated mycosis and mycobacteriosis in order to determine their potential clinical utility.