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The Search for Anticancer Agents from Tropical Plants

  • Joshua M. Henkin
  • Yulin Ren
  • Djaja Djendoel Soejarto
  • A. Douglas Kinghorn
Chapter
Part of the Progress in the Chemistry of Organic Natural Products book series (POGRCHEM, volume 107)

Abstract

Many of the clinically used anticancer agents in Western medicine are derived from secondary metabolites found in terrestrial microbes, marine organisms, and higher plants, with additional compounds of this type being currently in clinical trials. If plants are taken specifically, it is generally agreed that the prospects of encountering enhanced small organic-molecule chemical diversity are better if tropical rather than temperate species are investigated in drug discovery efforts. Plant collection in tropical source countries requires considerable preparation and organization to conduct in a responsible manner that abides by the provisions of the 1992 Rio Convention of Biological Diversity and the 2010 Nagoya Protocol on Access to Genetic Resources. Correct taxonomic identifications and enhanced procedures for processing and documenting plant samples when collected in often difficult terrain are required. Phytochemical aspects of the work involve solvent fractionation, known compound dereplication, preliminary in vitro testing, and prioritization, leading to “activity-guided fractionation”, compound structure determination, and analog development. Further evaluation of lead compounds requires solubility, formulation, preliminary pharmacokinetics, and in vivo testing in suitable models. Covering the work of the authors carried out in two sequential multidisciplinary, multi-institutional research projects, examples of very promising compounds discovered from plants acquired from Africa, Southeast Asia, the Americas, and the Caribbean region, and with potential anticancer activity will be mentioned. These include plant secondary metabolites of the diphyllin lignan, cyclopenta[b]benzofuran, triterpenoid, and tropane alkaloid types.

Keywords

Tropical plants Anticancer agents Relevant international conventions Plant collection logistics Taxonomic identification Laboratory processing Lead bioactive compound examples 

Notes

Acknowledgments

The authors of this chapter wish to acknowledge generous financial support through National Cooperative Drug Discovery Groups (NCDDG) project U01/U19 CA52956 (1990–2005) and program project grant P01-CA125066 (2007–2019) from the National Cancer Institute, National Institutes of Health, Bethesda, Maryland, U.S.A. We are extremely grateful to our taxonomic collaborators in many countries during the implementation of the NCDDG project, in particular, the late Dr. Leonardus Kardono and the late Dr. Soedarsono Riswan (Indonesia), Dr. Thawatchai Santisuk and Prof. Vichai Reutrakul (Thailand), Prof. Tangai E. Chagwedera (Zimbabwe), Dr. Domingo A. Madulid (Philippines), Ricardo Garcia (Dominican Republic), Prof. Rosa Pinos (Ecuador), Igr. Agr. Jose Castillo (Guatemala), Dr. R. Mukherjee (Brazil), Dr. Randrianaivo (Madagascar), Dr. T. Gözler and Dr. Abdulkerim Alpinas (Turkey), Dr. M.P. Gupta (Panama), Dr. I. Mbenkum (Cameroon), Dr. G. Mora (Costa Rica), and Dr. Lohi Matainaho (Papua New Guinea). The plants mentioned in this chapter that were collected in Vietnam and Laos were obtained under agreements between the University of Illinois at Chicago and the Institute of Ecology and Biological Resources (IEBR) of the Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam, and the Institute of Traditional Medicine (ITM), Ministry of Health, Vientiane, Lao PDR. We wish to express our thanks to Prof. Le Xuan Canh (former Director of IEBR) and Prof. Tran Huy Thai (present Director of IEBR), and to Prof. Kongmany Sydara (Director of ITM) for their collaboration, and to Dr. Tran Ngoc Ninh (IEBR) for his support and cooperation in the implementation of fieldwork in Vietnam. We wish to thank many present and former highly accomplished faculty, staff, and industrial colleagues, as well as postdoctoral associates, and graduate and undergraduate students who have participated in these collaborative projects to date, and whose names are included in the bibliography below. The two senior authors of this chapter (D.D.S. and A.D.K.) are particularly grateful to the late Dr. Norman R. Farnsworth, formerly Distinguished University Professor and Director, Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, for introducing them both in the 1970s to the scientific investigation of plants as potential anticancer agents.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Joshua M. Henkin
    • 1
  • Yulin Ren
    • 2
  • Djaja Djendoel Soejarto
    • 1
  • A. Douglas Kinghorn
    • 2
  1. 1.Department of Medicinal Chemistry and PharmacognosyCollege of Pharmacy, University of Illinois at ChicagoChicagoUSA
  2. 2.Medicinal Chemistry and PharmacognosyCollege of Pharmacy, The Ohio State UniversityColumbusUSA

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