Chemistry and the Potential Antiviral, Anticancer, and Anti-Inflammatory Activities of Cardiotonic Steroids Derived from Toads

Hesham R El-Seedi; Nermeen Yosri; Bishoy El-Aarag; Shaymaa H Mahmoud; Ahmed Zayed; Ming Du; Aamer Saeed; Syed G Musharraf; Islam M El-Garawani; Mohamed R Habib; Haroon Elrasheid Tahir; Momtaz M Hegab; Xiaobo Zou; Zhiming Guo; Thomas Efferth; Shaden A M Khalifa

doi:10.3390/molecules27196586

Chemistry and the Potential Antiviral, Anticancer, and Anti-Inflammatory Activities of Cardiotonic Steroids Derived from Toads

Molecules. 2022 Oct 5;27(19):6586. doi: 10.3390/molecules27196586.

Authors

Hesham R El-Seedi^{1

2

3

4}, Nermeen Yosri^{5

6}, Bishoy El-Aarag^{7

8

9}, Shaymaa H Mahmoud¹⁰, Ahmed Zayed¹¹, Ming Du¹², Aamer Saeed¹³, Syed G Musharraf¹⁴, Islam M El-Garawani¹⁰, Mohamed R Habib¹⁵, Haroon Elrasheid Tahir⁶, Momtaz M Hegab⁵, Xiaobo Zou⁶, Zhiming Guo⁶, Thomas Efferth¹⁶, Shaden A M Khalifa¹⁷

Affiliations

¹ International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China.
² Pharmacognosy Group, Department of Pharmaceutical Biosciences, Biomedical Centre, Uppsala University, Box 591, SE 751 24 Uppsala, Sweden.
³ International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing (Jiangsu Education Department), Zhenjiang 212013, China.
⁴ Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt.
⁵ Chemistry Department of Medicinal and Aromatic Plants, Research Institute of Medicinal and Aromatic Plants (RIMAP), Beni-Suef University, Beni-Suef 62514, Egypt.
⁶ School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China.
⁷ Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt.
⁸ Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan.
⁹ Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA.
¹⁰ Zoology Department, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt.
¹¹ Pharmacognosy Department, College of Pharmacy, Tanta University, Elguish Street, Tanta 31527, Egypt.
¹² National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116024, China.
¹³ Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
¹⁴ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan.
¹⁵ Medical Malacology Department, Theodor Bilharz Research Institute, Imbaba, Giza 12411, Egypt.
¹⁶ Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, 55128 Mainz, Germany.
¹⁷ Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE 10691 Stockholm, Sweden.

Abstract

Cardiotonic steroids (CTS) were first documented by ancient Egyptians more than 3000 years ago. Cardiotonic steroids are a group of steroid hormones that circulate in the blood of amphibians and toads and can also be extracted from natural products such as plants, herbs, and marines. It is well known that cardiotonic steroids reveal effects against congestive heart failure and atrial fibrillation; therefore, the term "cardiotonic" has been coined. Cardiotonic steroids are divided into two distinct groups: cardenolides (plant-derived) and bufadienolides (mainly of animal origin). Cardenolides have an unsaturated five-membered lactone ring attached to the steroid nucleus at position 17; bufadienolides have a doubly unsaturated six-membered lactone ring. Cancer is a leading cause of mortality in humans all over the world. In 2040, the global cancer load is expected to be 28.4 million cases, which would be a 47% increase from 2020. Moreover, viruses and inflammations also have a very nebative impact on human health and lead to mortality. In the current review, we focus on the chemistry, antiviral and anti-cancer activities of cardiotonic steroids from the naturally derived (toads) venom to combat these chronic devastating health problems. The databases of different research engines (Google Scholar, PubMed, Science Direct, and Sci-Finder) were screened using different combinations of the following terms: "cardiotonic steroids", "anti-inflammatory", "antiviral", "anticancer", "toad venom", "bufadienolides", and "poison chemical composition". Various cardiotonic steroids were isolated from diverse toad species and exhibited superior anti-inflammatory, anticancer, and antiviral activities in in vivo and in vitro models such as marinobufagenin, gammabufotalin, resibufogenin, and bufalin. These steroids are especially difficult to identify. However, several compounds and their bioactivities were identified by using different molecular and biotechnological techniques. Biotechnology is a new tool to fully or partially generate upscaled quantities of natural products, which are otherwise only available at trace amounts in organisms.

Keywords: anti-inflammatory; anticancer; antiviral; bufadienolides; bufalin; bufotalin; cardiotonic steroids.

Publication types

Review

MeSH terms

Animals
Antiviral Agents
Biological Products*
Bufanolides* / chemistry
Bufonidae
Cardenolides / chemistry
Cardiac Glycosides* / pharmacology
Hormones
Humans
Lactones
Poisons*

Substances

Antiviral Agents
Biological Products
Bufanolides
Cardenolides
Cardiac Glycosides
Hormones
Lactones
Poisons

Grants and funding

This research received no external funding.