Apparicine is a

monoterpenoid Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear (acyclic) or contain rings (monocyclic and bicyclic). Modified terpenes, such as those containing oxygen funct ...

tricyclic

indole alkaloid Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known differ ...

. It is named after Apparicio Duarte, a Brazilian

botanist Botany, also called plant science, is the branch of natural science and biology studying plants, especially Plant anatomy, their anatomy, Plant taxonomy, taxonomy, and Plant ecology, ecology. A botanist or plant scientist is a scientist who s ...

who studied the ''

Aspidosperma ''Aspidosperma'' is a genus of flowering plant in the Dogbane family (biology), family (Apocynaceae), first described as a genus in 1824. It is native to South America, Central America, southern Mexico, and the West Indies. One Central American ...

'' species from which apparicine was first isolated. It was the first member of the vallesamine group of

s to be isolated and have its structure established, which was first published in 1965. It has also been known by the synonyms gomezine, pericalline, and tabernoschizine.

Biochemistry

The alkaloid has been isolated from seven species of ''Aspidosperma''. It is the principal alkaloid found in the

callus A callus (: calluses) is an area of thickened and sometimes hardened skin that forms as a response to repeated friction, pressure, or other irritation. Since repeated contact is required, calluses are most often found on the feet and hands, b ...

of '' Tabernaemontana elegans'', and has also been identified in other ''

Tabernaemontana ''Tabernaemontana'' is a genus of flowering plants in the family Apocynaceae. It has a pan-tropical distribution, found in Asia, Africa, Australia, North America, South America, and islands of the Indian and Pacific Oceans. These plants are everg ...

'' species, including '' T. africana'', '' T. divaricata'', '' T. orientalis'', and '' T. pachysiphon''. In studies of ''T. pachysiphon'', it was found that alkaloid content including that of apparicine was greatest in young leaves and leaves receiving greater shade, and varied with leaf age, plant age, and provenance. Research on '' Aspidosperma pyricollum'' has led to the discovery that apparicine is

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

ed from

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

by "loss of C-2 and retention of C-3". The biosynthesis of apparicine requires alteration of the usual

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

side chain In organic chemistry and biochemistry, a side chain is a substituent, chemical group that is attached to a core part of the molecule called the "main chain" or backbone chain, backbone. The side chain is a hydrocarbon branching element of a mo ...

with loss of C-1.

Structure determination

Its structure was established through the methods of

chemical decomposition Chemical decomposition, or chemical breakdown, is the process or effect of simplifying a single molecular entity, chemical entity (normal molecule, reaction intermediate, etc.) into two or more fragments. Chemical decomposition is usually regarded ...

, and the nascent field of nuclear magnetic resonance (NMR) decoupling using the ¹H isotope of hydrogen. Ultraviolet–visible spectroscopy showed that apparicine has a similar UV absorption to uleine, and their

chromophore A chromophore is the part of a molecule responsible for its color. The word is derived . The color that is seen by our eyes is that of the light not Absorption (electromagnetic radiation), absorbed by the reflecting object within a certain wavele ...

s were found to be identical. NMR decoupling experiments revealed that apparicine lacks an ''N''-methyl signal and has one methylenic carbon atom between the nitrogen atom and the

indole Indole is an organic compound with the formula . Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole ...

rings, allowing researchers to distinguish it from uleine. This was a notable early use of NMR decoupling to determine a chemical structure. Its carbon

skeleton A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fra ...

was found to be related but different from that of uleine, and the structures of vallesamine and O-acetyl-vallesamine to be related to apparicine.

Dehydrogenation In chemistry, dehydrogenation is a chemical reaction that involves the removal of hydrogen, usually from an organic molecule. It is the reverse of hydrogenation. Dehydrogenation is important, both as a useful reaction and a serious problem. At ...

of apparicine followed by

oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

with

permanganate A permanganate () is a chemical compound with the manganate(VII) ion, , the conjugate base of permanganic acid. Because the manganese atom has a +7 oxidation state, the permanganate(VII) ion is a strong oxidising agent. The ion is a transition ...

allowed location of the two

piperidine Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless liquid with an odor de ...

ring carbon substituents.

Applications

Apparicine may have several potential applications. In

cell culture Cell culture or tissue culture is the process by which cell (biology), cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been Cell isolation, isolated from living tissue, ...

s, it has shown

cytotoxicity Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of d ...

against the experimental lymphocytic leukemia P388

cell line An immortalised cell line is a population of cells from a multicellular organism that would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...

. It exhibits strong activity against

poliovirus Poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species '' Enterovirus C'', in the family of '' Picornaviridae''. There are three poliovirus serotypes, numbered 1, 2, and 3. Poliovirus is composed ...

type 3 (PV3), and has moderate to strong activity against some human

pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...

s. It is also active at

opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostati ...

s and has micromolar

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for

adenosine receptor The adenosine receptors (or P1 receptors) are a class of Purinergic receptor, purinergic G protein-coupled receptors with adenosine as the endogenous ligand (biochemistry), ligand. There are four known types of adenosine receptors in humans: Aden ...

s. Apparicine has local

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

properties. It inhibited xanthine oxidase as potently as allopurinol (IC₅₀ = 0.65 μM).

Notes

References

* * * * * * * * * * * * *

External links

(-)-Apparicine
in the

United States Environmental Protection Agency The Environmental Protection Agency (EPA) is an independent agency of the United States government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it began operation on De ...