Cardenolide

Last updated
Cardenolide
Cardenolide.png
Names
IUPAC name
3-[(8R,9S,10S,13S,14R,17S)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
UNII
  • InChI=1S/C23H34O2/c1-22-11-4-3-5-16(22)6-7-17-19-9-8-18(15-13-21(24)25-14-15)23(19,2)12-10-20(17)22/h4,11,15-20H,3,5-10,12-14H2,1-2H3/t15-,16?,17-,18+,19+,20-,22-,23+/m0/s1 Yes check.svgY
    Key: NMLOFHCUVXKTGV-OCYOQFCJSA-N Yes check.svgY
  • InChI=1/C23H34O2/c1-22-11-4-3-5-16(22)6-7-17-19-9-8-18(15-13-21(24)25-14-15)23(19,2)12-10-20(17)22/h4,11,15-20H,3,5-10,12-14H2,1-2H3/t15-,16?,17-,18+,19+,20-,22-,23+/m0/s1
    Key: NMLOFHCUVXKTGV-OCYOQFCJBM
  • CC12CCCCC1CCC3C2CCC4(C3C=CC4C5CC(=O)OC5)C
  • C[C@]52/C=C\CCC5CC[C@H]1[C@H]3CC[C@@H]([C@@]3(C)CC[C@@H]12)[C@H]4CC(=O)OC4
Properties
C23H34O2
Molar mass 342.51486
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

A cardenolide is a type of steroid. Many plants contain derivatives, collectively known as cardenolides, including many in the form of cardenolide glycosides (cardenolides that contain structural groups derived from sugars). Cardenolide glycosides are often toxic; specifically, they are heart-arresting. Cardenolides are toxic to animals through inhibition of the enzyme Na+/K+‐ATPase, which is responsible for maintaining the sodium and potassium ion gradients across the cell membranes. [1]

Contents

Etymology

The term derives from card- "heart" (from Greek καρδία kardiā) and the suffix -enolide, referring to the lactone ring at C17. [2] Cardenolides are a class of steroids (or aglycones if viewed as cardiac glycoside constituents), and cardenolides are a subtype of this class (see MeSH D codes list).

Structure

Cardenolides are C(23)-steroids with methyl groups at C-10 and C-13 and a five-membered lactone (specifically a butenolide) at C-17. They are aglycone constituents of cardiac glycosides and must have at least one double bond in the molecule. The class includes cardadienolides and cardatrienolides. Members include:

Bufadienolide and marinobufagenin are similar in structure and function.

Cardanolide is the same core structure, but has a saturated lactone ring instead of one containing an alkene.

As defense mechanism

Some plant and animal species use cardenolides as defense mechanisms, notably the milkweed butterflies. [3] Species such as the monarch, queen, and plain tiger ingest the cardenolides contained in the milkweeds (Asclepias) that they mostly feed on and sequester as larvae for defense as adults. [1] [4] The cardenolide content in butterflies deters most vertebrate predators, except a few which have evolved to become cardenolide-tolerant, such as the black-backed orioles (Icterus abeillei Lesson) and black-headed grosbeaks (Pheucticus melanocephalus Swainson) that account for 60% of monarch butterfly mortalities in the overwintering sites in central Mexico. In addition to milkweeds and other members of the Apocynaceae, plants in at least 12 botanical families have convergently evolved cardenolides, used as a chemical defense mechanism against herbivores. [5] Herbivorous insects in six different orders have evolved resistance to the toxic effects of cardenolides in the food sources that they use. These cardenolide-resistant insect species convergently evolved this resistance through similar amino-acid substitutions in the alpha subunit of the enzyme Na+/K+‐ATPase. [6] [7] [8]

Related Research Articles

<span class="mw-page-title-main">Cardiac glycoside</span> Class of organic compounds

Cardiac glycosides are a class of organic compounds that increase the output force of the heart and decrease its rate of contractions by inhibiting the cellular sodium-potassium ATPase pump. Their beneficial medical uses are as treatments for congestive heart failure and cardiac arrhythmias; however, their relative toxicity prevents them from being widely used. Most commonly found as secondary metabolites in several plants such as foxglove plants, these compounds nevertheless have a diverse range of biochemical effects regarding cardiac cell function and have also been suggested for use in cancer treatment.

<i>Erysimum</i> Genus of flowering plants

Erysimum, or wallflower, is a genus of flowering plants in the cabbage family, Brassicaceae. It includes more than 150 species, both popular garden plants and many wild forms. The genus Cheiranthus is sometimes included here in whole or in part. Erysimum has since the early 21st century been ascribed to a monogeneric cruciferous tribe, Erysimeae, characterised by sessile, stellate (star-shaped) and/or malpighiaceous (two-sided) trichomes, yellow to orange flowers and multiseeded siliques.

<i>Asclepias tuberosa</i> Species of flowering plant

Asclepias tuberosa, commonly known as butterfly weed, is a species of milkweed native to eastern and southwestern North America. It is commonly known as butterfly weed because of the butterflies that are attracted to the plant by its color and its copious production of nectar.

<span class="mw-page-title-main">Sodium–potassium pump</span> Enzyme found in the membrane of all animal cells

The sodium–potassium pump is an enzyme found in the membrane of all animal cells. It performs several functions in cell physiology.

<span class="mw-page-title-main">Monarch butterfly</span> Milkweed butterfly in the family Nymphalidae

The monarch butterfly or simply monarch is a milkweed butterfly in the family Nymphalidae. Other common names, depending on region, include milkweed, common tiger, wanderer, and black-veined brown. It is amongst the most familiar of North American butterflies and an iconic pollinator, although it is not an especially effective pollinator of milkweeds. Its wings feature an easily recognizable black, orange, and white pattern, with a wingspan of 8.9–10.2 cm (3.5–4.0 in). A Müllerian mimic, the viceroy butterfly, is similar in color and pattern, but is markedly smaller and has an extra black stripe across each hindwing.

<i>Asclepias</i> Genus of flowering plants

Asclepias is a genus of herbaceous, perennial, flowering plants known as milkweeds, named for their latex, a milky substance containing cardiac glycosides termed cardenolides, exuded where cells are damaged. Most species are toxic to humans and many other species, primarily due to the presence of cardenolides. However, as with many such plants, some species feed upon them or from them. The most notable of them is the monarch butterfly, which uses and requires certain milkweeds as host plants for their larvae.

<span class="mw-page-title-main">Glycoside</span> Molecule in which a sugar is bound to another functional group

In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. These can be activated by enzyme hydrolysis, which causes the sugar part to be broken off, making the chemical available for use. Many such plant glycosides are used as medications. Several species of Heliconius butterfly are capable of incorporating these plant compounds as a form of chemical defense against predators. In animals and humans, poisons are often bound to sugar molecules as part of their elimination from the body.

Chemical ecology is the study of chemically mediated interactions between living organisms, and the effects of those interactions on the demography, behavior and ultimately evolution of the organisms involved. It is thus a vast and highly interdisciplinary field. Chemical ecologists seek to identify the specific molecules that function as signals mediating community or ecosystem processes and to understand the evolution of these signals. The substances that serve in such roles are typically small, readily-diffusible organic molecules, but can also include larger molecules and small peptides.

<span class="mw-page-title-main">Phytochemistry</span> Study of phytochemicals, which are chemicals derived from plants

Phytochemistry is the study of phytochemicals, which are chemicals derived from plants. Phytochemists strive to describe the structures of the large number of secondary metabolites found in plants, the functions of these compounds in human and plant biology, and the biosynthesis of these compounds. Plants synthesize phytochemicals for many reasons, including to protect themselves against insect attacks and plant diseases. The compounds found in plants are of many kinds, but most can be grouped into four major biosynthetic classes: alkaloids, phenylpropanoids, polyketides, and terpenoids.

<span class="mw-page-title-main">Cerberin</span> Chemical compound

Cerberin is a type of cardiac glycoside, a steroidal class found in the seeds of the dicotyledonous angiosperm genus Cerbera; including the suicide tree and the sea mango. This class includes digitalis-like agents, channel-blockers that as a group have found historic uses as cardiac treatments, but which at higher doses are extremely toxic; in the case of cerberin, consumption of the C. odollam results in poisoning with presenting nausea, vomiting, and abdominal pain, often leading to death. The natural product has been structurally characterized, its toxicity is clear—it is often used as an intentional human poison in third-world countries, and accidental poisonings with fatalities have resulted from individuals even indirectly consuming the agent—but its potentially therapeutic pharmacologic properties are very poorly described.

<span class="mw-page-title-main">Black-headed grosbeak</span> Species of bird

The black-headed grosbeak is a medium-sized, seed-eating bird in the family Cardinalidae. It is sometimes considered conspecific with the rose-breasted grosbeak with which it hybridizes on the American Great Plains.

Herbivores are dependent on plants for food, and have coevolved mechanisms to obtain this food despite the evolution of a diverse arsenal of plant defenses against herbivory. Herbivore adaptations to plant defense have been likened to "offensive traits" and consist of those traits that allow for increased feeding and use of a host. Plants, on the other hand, protect their resources for use in growth and reproduction, by limiting the ability of herbivores to eat them. Relationships between herbivores and their host plants often results in reciprocal evolutionary change. When a herbivore eats a plant it selects for plants that can mount a defensive response, whether the response is incorporated biochemically or physically, or induced as a counterattack. In cases where this relationship demonstrates "specificity", and "reciprocity", the species are thought to have coevolved. The escape and radiation mechanisms for coevolution, presents the idea that adaptations in herbivores and their host plants, has been the driving force behind speciation. The coevolution that occurs between plants and herbivores that ultimately results in the speciation of both can be further explained by the Red Queen hypothesis. This hypothesis states that competitive success and failure evolve back and forth through organizational learning. The act of an organism facing competition with another organism ultimately leads to an increase in the organism's performance due to selection. This increase in competitive success then forces the competing organism to increase its performance through selection as well, thus creating an "arms race" between the two species. Herbivores evolve due to plant defenses because plants must increase their competitive performance first due to herbivore competitive success.

<i>Asclepias curassavica</i> Species of flowering plant

Asclepias curassavica, commonly known as tropical milkweed, is a flowering plant species of the milkweed genus, Asclepias. It is native to the American tropics and has a pantropical distribution as an introduced species. Other common names include bloodflower or blood flower, cotton bush, hierba de la cucaracha, Mexican butterfly weed, redhead, scarlet milkweed, and wild ipecacuanha.

<span class="mw-page-title-main">Daigremontianin</span> Chemical compound

Daigremontianin is a bufadienolide. Bufadienolides are steroids and cardiac glycoside aglycones that are similar to cardenolides, differing only in the structure of the C-17 substituent on the D ring. This chemical has been found to be toxic in experiments on mice. It is one of five bufadienolides that have been isolated from Kalanchoe daigremontiana.

<span class="mw-page-title-main">Bufadienolide</span> Chemical compound

Bufadienolide is a chemical compound with steroid structure. Its derivatives are collectively known as bufadienolides, including many in the form of bufadienolide glycosides. These are a type of cardiac glycoside, the other being the cardenolide glycosides. Both bufadienolides and their glycosides are toxic; specifically, they can cause an atrioventricular block, bradycardia, ventricular tachycardia, and possibly lethal cardiac arrest.

<i>Calotropis gigantea</i> Species of plant

Calotropis gigantea, the crown flower, is a species of Calotropis native to Cambodia, Vietnam, Bangladesh, Indonesia, Malaysia, Thailand, Sri Lanka, India, China, Pakistan, and Nepal.

<i>Erysimum cheiranthoides</i> Species of flowering plant

Erysimum cheiranthoides, the treacle-mustard,wormseed wallflower, or wormseed mustard is a species of Erysimum native to most of central and northern Europe and northern and central Asia. Like other Erysimum species, E. cheiranthoides accumulates two major classes of defensive chemicals: glucosinolates and cardiac glycosides.

<span class="mw-page-title-main">Escape and radiate coevolution</span>

Escape and radiate coevolution is a hypothesis proposing that a coevolutionary 'arms-race' between primary producers and their consumers contributes to the diversification of species by accelerating speciation rates. The hypothesized process involves the evolution of novel defenses in the host, allowing it to "escape" and then "radiate" into differing species.

<span class="mw-page-title-main">Anurag Agrawal (ecologist)</span> American ecologist and biologist (born 1972)

Anurag Agrawal is an American professor of ecology, evolutionary biology, and entomology who has written over a 150 peer-reviewed articles, which earned him an h-index of 92. He is the author of a popular science book, Monarchs and Milkweeds from Princeton University Press, and is currently the James Alfred Perkins Professor of Environmental Studies at Cornell University.

<span class="mw-page-title-main">Calotropin</span> Chemical compound

Calotropin is a toxic cardenolide found in plants in the family Asclepiadoideae. In extreme cases, calotropin poisoning can cause respiratory and cardiac failure. Accidental poisoning is common in livestock who have ingested milkweed. Calotropin is commonly stored as a defense mechanism by insects that eat milkweeds as their main food source.

References

  1. 1 2 Agrawal, Anurag A.; Petschenka, Georg; Bingham, Robin A.; Weber, Marjorie G.; Rasmann, Sergio (April 2012). "Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions". The New Phytologist. 194 (1): 28–45. doi: 10.1111/j.1469-8137.2011.04049.x . ISSN   1469-8137. PMID   22292897.
  2. Naudé, T. W. (1977). "The occurrence and significance of South African cardiac glycosides". Journal of the South African Biological Society. 18: 7.
  3. "Interactions with Milkweed | Breeding / Life Cycle | Biology & Natural History | Biology & Research | Monarch Lab". Archived from the original on 2014-02-20. Retrieved 2014-03-25.
  4. Edgar, J. A.; Cockrum, P. A.; Frahn, J. L. (1976-12-01). "Pyrrolizidine alkaloids inDanaus plexippus L. andDanaus chrysippus L.". Experientia. 32 (12): 1535–1537. doi:10.1007/bf01924437. ISSN   0014-4754. S2CID   27664625.
  5. Agrawal, Anurag A. (2012). "Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions". New Phytologist. 194 (1): 28–45. doi: 10.1111/j.1469-8137.2011.04049.x . PMID   22292897.
  6. Zhen, Ying; Aardema, Matthew L.; Medina, Edgar M.; Schumer, Molly; Andolfatto, Peter (2012-09-28). "Parallel Molecular Evolution in an Herbivore Community". Science. 337 (6102): 1634–1637. Bibcode:2012Sci...337.1634Z. doi:10.1126/science.1226630. ISSN   0036-8075. PMC   3770729 . PMID   23019645.
  7. Dobler, S., Dalla, S., Wagschal, V., & Agrawal, A. A. (2012). Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na,K-ATPase. Proceedings of the National Academy of Sciences, 109(32), 13040–13045. https://doi.org/10.1073/pnas.1202111109
  8. Yang, L.; Ravikanthachari, N.; Mariño-Pérez, R.; Deshmukh, R.; Wu, M.; Rosenstein, A.; Kunte, K.; Song, H.; Andolfatto, P. (2019). "Predictability in the evolution of Orthopteran cardenolide insensitivity". Philosophical Transactions of the Royal Society of London, Series B. 374 (1777): 20180246. doi:10.1098/rstb.2018.0246. PMC   6560278 . PMID   31154978.