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 ...

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 differe ...

. It is named after Apparicio Duarte, a Brazilian

botanist Botany, also called , plant biology or phytology, is the science of plant life and a branch of biology. A botanist, plant scientist or phytologist is a scientist who specialises in this field. The term "botany" comes from the Ancient Greek wo ...

who studied the ''

Aspidosperma ''Aspidosperma'' is a genus of flowering plant in the family Apocynaceae, first described as a genus in 1824. It is native to South America, Central America, southern Mexico, and the West Indies The West Indies is a subregion of North A ...

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

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

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 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, but they may o ...

of ''

Tabernaemontana elegans ''Tabernaemontana elegans'', the toad tree, is a shrub or small tree in the family Apocynaceae. It is native to eastern Africa. Description ''Tabernaemontana elegans'' grows up to tall, with a trunk diameter of up to . Its fragrant flowers feat ...

'', 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 a wide assortment of oceanic islands. These plants are evergreen ...

'' 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 is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

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 aromatic ...

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 f ...

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

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 chemical entity (normal molecule, reaction intermediate, etc.) into two or more fragments. Chemical decomposition is usually regarded and defined as t ...

, and the nascent field of nuclear magnetic resonance (NMR) decoupling using the ¹H isotope of hydrogen.

Ultraviolet–visible spectroscopy UV spectroscopy or UV–visible spectrophotometry (UV–Vis or UV/Vis) refers to absorption spectroscopy or reflectance spectroscopy in part of the ultraviolet and the full, adjacent visible regions of the electromagnetic spectrum. Being relativel ...

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 color that is seen by our eyes is the one not absorbed by the reflecting object within a certain wavelength spectrum of visible light. The chromophore is a region in the molec ...

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 aromatic heterocyclic organic compound with the formula C8 H7 N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environmen ...

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 an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

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, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

with

permanganate A permanganate () is a chemical compound containing the manganate(VII) ion, , the conjugate base of permanganic acid. Because the manganese atom is in the +7 oxidation state, the permanganate(VII) ion is a strong oxidizing agent. The ion is a tra ...

allowed location of the two

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

ring carbon substituents.

Applications

Apparicine may have several potential applications. In

cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...

s, it has shown

cytotoxicity Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

against the experimental

lymphocytic leukemia Lymphoid leukemias are a group of leukemias affecting circulating lymphocytes, a type of white blood cell. The lymphocytic leukemias are closely related to lymphomas of the lymphocytes, to the point that some of them are unitary disease entities t ...

P388 The NCI-60 cancer cell line panel is a group of 60 human cancer cell lines used by the National Cancer Institute (NCI) for the screening of compounds to detect potential anticancer activity. Purpose The screening procedure is called the NCI- ...

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

. It exhibits strong activity against

poliovirus A 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: types 1, 2, and 3. Poliovirus is composed of an ...

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

pathogen In biology, a pathogen ( el, πάθος, "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 ...

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 somatostatin r ...

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 Partn ...

for

adenosine receptor The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand. There are four known types of adenosine receptors in humans: A1, A2A, A2B and A3; each is encoded by a di ...

s. Apparicine has local

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

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

Notes

References

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

External links

(-)-Apparicine
at the

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