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

Abstract

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 analogs, 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 analog synthesis, as well as structure-activity relationship and mechanism of action studies. Current clinical trials 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 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 clinical trials candidates will also be discussed.

Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect

“…In the continuing search for agents that may treat or ameliorate the affiliation of cancer, natural products have provided an endless supply of active compounds that are increasingly being exploited. In many cases, this quest has already resulted in leads and scaffolds for drugs [1][2][3] and many reports highlight the use of plant-derived compounds as anticancer drugs 4,5 that contribute to new leads in clinical trials. 6 Anisomelic acid (AA) (Fig.…”

Biotransformation of sclareolide by filamentous fungi: cytotoxic evaluations of the derivatives

“…[7][8][9] A major challenge for the transformations using biocatalytic methods is to determine the appropriate microorganism and conditions, so, we proceeded with the screening using different fungal strains and media, with sclareolide (1, Figure 1) as substrate and then the processes were scaled up. In addition and in the search of new bioactive agents from natural products, 10,11 the cytotoxic evaluation against several human tumor cell lines of 1 and the obtained products (2, 4, 16-19) were carried up. Here we report our results.…”

Bracken-fern Extracts Induce Cell Cycle Arrest and Apoptosis in Certain Cancer Cell Lines

“…Reagents with natural origin continue to be of preferred priority in the drug screening programs (Lee, 2004). Today, the plants are well documented as a good source of biologically active compounds (Iranshahi et al, 2007;.…”