Cardenolides: Insights from chemical structure and pharmacological utility

Hesham R El-Seedi; Shaden A M Khalifa; Eman A Taher; Mohamed A Farag; Aamer Saeed; Mohamed Gamal; Mohamed-Elamir F Hegazy; Diaa Youssef; Syed G Musharraf; Muaaz M Alajlani; Jianbo Xiao; Thomas Efferth

doi:10.1016/j.phrs.2018.12.015

Cardenolides: Insights from chemical structure and pharmacological utility

Pharmacol Res. 2019 Mar:141:123-175. doi: 10.1016/j.phrs.2018.12.015. Epub 2018 Dec 21.

Authors

Affiliations

¹ Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-75123, Uppsala, Sweden; Chemistry Department, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; H. E. J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom, Egypt. Electronic address: hesham.el-seedi@ilk.uu.se.
² Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91, Stockholm, Sweden.
³ National Organization for Drug Control and Research (NODCAR), P.O. Box 29, Cairo, Egypt; Department of Chemistry, Royal Institute of Technology, KTH, Sweden.
⁴ Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr el Aini St., 11562 Cairo, Egypt; Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, New Cairo, Egypt.
⁵ Chemistry Department, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
⁶ Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom, Egypt.
⁷ Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt; Department of Pharmaceutical Biology, Institute of Pharmacy, Johannes Gutenberg University, 55128 Mainz, Germany.
⁸ Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia.
⁹ H. E. J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.
¹⁰ Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-75123, Uppsala, Sweden.
¹¹ Institute of Chinese Medical Sciences, State Key Laboratory of Quality Control in Chinese Medicine, University of Macau, Macau, China.
¹² Department of Pharmaceutical Biology, Institute of Pharmacy, Johannes Gutenberg University, 55128 Mainz, Germany.

PMID: 30579976
DOI: 10.1016/j.phrs.2018.12.015

Abstract

Cardiac glycosides (CGs) are a class of naturally occurring steroid-like compounds, and members of this class have been in clinical use for more than 1500 years. They have been used in folk medicine as arrow poisons, abortifacients, heart tonics, emetics, and diuretics as well as in other applications. The major use of CGs today is based on their ability to inhibit the membrane-bound Na⁺/K⁺-ATPase enzyme, and they are regarded as an effective treatment for congestive heart failure (CHF), cardiac arrhythmia and atrial fibrillation. Furthermore, increasing evidence has indicated the potential cytotoxic effects of CGs against various types of cancer. In this review, we highlight some of the structural features of this class of natural products that are crucial for their efficacy, some methods of isolating these compounds from natural resources, and the structural elucidation tools that have been used. We also describe their physicochemical properties and several modern biotechnological approaches for preparing CGs that do not require plant sources.

Keywords: Cardiac glycosides; Chemical property space; Heart failure; Isolation.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cardenolides / chemistry*
Cardenolides / pharmacology*
Cardiovascular Agents / chemistry
Cardiovascular Agents / pharmacology
Diuretics / chemistry
Diuretics / pharmacology
Humans

Substances

Antineoplastic Agents
Cardenolides
Cardiovascular Agents
Diuretics