Discovery and Development of Natural Product-Derived Chemotherapeutic Agents Based on a Medicinal Chemistry Approach

Medicinal plants have long been in 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 oil 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, dithiophenecdiones, 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]low in phase IIb trials for treating AIDS. Bevirimat is also file first ill a new class of HIV drug candidates called maturation inhibitors, In addition all etoposide GL-31, progressed to anticancer phase 11 clinical trials, and the curcumin analogue JC-9 is in phase II clinical trials for treating aene and in development for. trials against prostate cancer. The discovery and development of these Clinical trial candidates Will also be discussed.