Medicinal plants have long been an excellent source of
pharmaceutical agents. Accordingly, the long-term objectives of the author's research program are to discover and design new chemotherapeutic agents based on
plant-derived compound leads by using a medicinal chemistry approach, which is a combination of chemistry and biology. Different examples of promising bioactive natural products and their synthetic analogues, including
sesquiterpene lactones,
quassinoids,
naphthoquinones, phenylquinolones, dithiophenediones,
neo-tanshinlactone,
tylophorine,
suksdorfin, DCK, and DCP, will be presented with respect to their discovery and preclinical development as potential clinical trial candidates. Research approaches include bioactivity- or mechanism of action-directed isolation and characterization of active compounds, rational
drug design-based modification and analogue synthesis, and structure-activity relationship and mechanism of action studies. Current clinical trial agents discovered by the Natural Products Research Laboratories, University of North Carolina, 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 analogue,
GL-331, progressed to anticancer phase II clinical trials, and the
curcumin analogue 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 clinical trial candidates will also be discussed.