Session Speaker

Novel Anti-Opportunistic Infection Agents with Lower Cytotoxicity
Seth Y. Ablordeppey, Xue Y. Zhu, Eyunni V. Kumar, Reddy Etukala, Melissa Jacob, Shabana Khan and Larry Walker
USA

The natural product, cryptolepine (I) has attracted tremendous attention as a result of its anti-bacterial, antifungal and antiprotozoal activities among others. Limited Structure-Activity Relationship (SAR) studies revealed that structural modifications on the tetracyclic ring often led to significant changes in biological activity. The main objective of this study was to optimize the anti-opportunistic activity and lower toxicity through a more extended SAR studies. Using rational drug design strategies, several compounds were proposed, synthesized and evaluated indicating that benzothienoquinolinium and angular indoloquinolinium species and their ring-opened analogs constitute new anti-infectives with lower cytotoxicity than cryptolepine. Indeed, several of the new compounds are over 300-fold more potent than the original natural product. Further studies in animal models of cryptococcosis and candidiasis confirmed in vivo efficacy. A systematic presentation of the identification of the new anti-opportunistic agents will be discussed.