Discovery and development of plant-derived antitumor and anti-HIV clinical trials agents

Medicinal plants have long been an excellent source of pharmaceutical agents. Accordingly, the author's Natural Products Research Laboratories (NPRL) uses medicinal chemistry by combining chemistry and biology to discover and design new chemotherapeutic agents based on plant-derived compound leads. Research approaches include bioactivity- or mechanism of action-directed isolation and characterization of active compounds, rational drug design-based modification and analog synthesis, as well as structure-activity relationship and mechanism of action studies. Current clinical trials agents discovered by the NPRL include bevirimat (dimethyl succinyl betulinic acid), which is now in Phase IIb trials for treating AIDS. Bevirimat is also the first in a new class of HIV drug candidates called „maturation inhibitors“. In addition, an etoposide analog, GL-331, progressed to anticancer Phase II clinical trials, and the curcumin analog JC-9 is in Phase II clinical trials for treating acne and in development for trials against prostate cancer. The discovery and development of these and other clinical trials candidates will be discussed. (Aided by NIH grants CA-17625 and AI-33066).