Plant Secondary Metabolites as Potential Anticancer Agents and Cancer Chemopreventives

A Douglas Kinghorn

doi:10.3390/50300285

Abstract

A. Douglas KinghornProgram for Collaborative Research in the Pharmaceutical Sciences and Department of MedicinalChemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 SouthWood Street, Chicago, IL 60612, U.S.ATel.: (312) 996-0914, Fax: (312) 996-7107, E-mail: kinghorn@uic.eduThere is considerable interest in the screening of plant and other natural product extracts in moderndrug discovery programs, since structurally novel chemotypes with potent and selective biological ac-tivity may be obtained [1-4]. A consideration of biological activity in addition to the isolation andstructure elucidation stages in a phytochemical investigation may add a great deal to the overall scien-tific significance of the work. Phytochemists may gain considerable information by using panels ofsimple bioassays and/or more specialized in vitro bioassays to follow each step of a purification proce-dure [3]. In the following paragraphs, recent examples of bioactive compounds obtained in the author’slaboratory in projects directed towards the search for novel anticancer agents and cancer chemopre-ventives from higher plants will be presented.In the United States in 1999, it is estimated that over 1.2 million persons will be diagnosed with in-vasive forms of cancer, and over 1,500 people will die as a result of cancer each day [5]. Among manyrecent advances in cancer chemotherapy, plant natural products have played an important role in con-tributing to the arsenal of the approximately 60 cancer chemotherapeutic drugs on the market. For in-stance, in the United States, there are now four structural classes of plant anticancer agents available,constituted by the Catharanthus (Vinca) alkaloids (vinblastine, vincristine, vinorelbine), the epipodo-phyllotoxins (etoposide, etoposide phosphate, teniposide), the taxanes (paclitaxel and docetaxel), andthe camptothecin derivatives (irinotecan and topotecan) [6]. Several other plant-derived compoundsare currently in preclinical and clinical trials [6,7].As part of a National Cooperative Natural Products Drug Discovery Group (NCNPDDG) researchproject funded by the United States National Cancer Institute (1995-2000), our collaborative team atthe College of Pharmacy, University of Illinois at Chicago (Chicago, Illinois), and Research TriangleInstitute (Research Triangle Park, North Carolina), and Bristol-Myers Squibb (Princeton, New Jersey)is evaluating about 400 plant samples per year, with the aim of discovering and evaluating novel plant-derived anticancer agents. During the funding period 1990-1995, the industrial partner was GlaxoWellcome Medicines Research Centre (Sevenage, U.K.), and past progress made in the project hasbeen reviewed [8]. Since 1995, the primary plant samples have been collected in the Dominican Re-public, Peru, and Indonesia. Plant recollections have taken place mainly in Thailand and Zimbabwe in

Highlights

In the United States in 1999, it is estimated that over 1.2 million persons will be diagnosed with invasive forms of cancer, and over 1,500 people will die as a result of cancer each day [5]
A consideration of biological activity in addition to the isolation and structure elucidation stages in a phytochemical investigation may add a great deal to the overall scientific significance of the work
Among many recent advances in cancer chemotherapy, plant natural products have played an important role in contributing to the arsenal of the approximately 60 cancer chemotherapeutic drugs on the market

Summary

Introduction

In the United States in 1999, it is estimated that over 1.2 million persons will be diagnosed with invasive forms of cancer, and over 1,500 people will die as a result of cancer each day [5]. There is considerable interest in the screening of plant and other natural product extracts in modern drug discovery programs, since structurally novel chemotypes with potent and selective biological activity may be obtained [1,2,3,4].

Results

Conclusion