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

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

Hesham R El-Seedi  1   2   3   4 , Nermeen Yosri  5   6 , Bishoy El-Aarag  7   8   9 , Shaymaa H Mahmoud  10 , Ahmed Zayed  11 , Ming Du  12 , Aamer Saeed  13 , Syed G Musharraf  14 , Islam M El-Garawani  10 , Mohamed R Habib  15 , Haroon Elrasheid Tahir  6 , Momtaz M Hegab  5 , Xiaobo Zou  6 , Zhiming Guo  6 , Thomas Efferth  16 , Shaden A M Khalifa  17
Affiliations
Review

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

Hesham R El-Seedi et al. Molecules. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) The basic steroid aglycone unit of cardiotonic steroids and their types, cardenolides and bufadienolides; (B) numbered chemical structure of the bufadienolide aglycone or steroidal nucleus, i.e., the main type of cardiotonic steroids (n denotes the number of the sugar monomer in the cardiac glycoside structures (n = 1–3)).
Figure 2
Figure 2
Proposed mechanism of the biosynthesis of bufadienolides by toads (Bufo marinus) [29].
Figure 3
Figure 3
Proposed mechanism of the biosynthesis of marinobufagenin by toads (Bufo marinus) [30].
Figure 4
Figure 4
Chemical structures of most common compounds isolated from venom of toads.
Figure 4
Figure 4
Chemical structures of most common compounds isolated from venom of toads.
See this image and copyright information in PMC

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