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The enediynes are a class of cyclic molecules whose core ring contains an alkene conjugated to two alkynes. This core ring consists of a total of either nine or ten members. Other functional groups are usually attached to the nine- or ten-membered ring, providing each enediyne with additional chemical properties.

Since the discovery of calicheamicin and esperamicin in 1987, several more enediynes have been discovered as natural products in bacteria. Synthetic enediynes have also been designed to improve the functionality of the naturally occurring enediynes.

Enediynes are most notable for their limited use as antitumor antibiotics. They are efficient at inducing apoptosis in cells, but cannot differentiate cancerous cells from healthy cells. Consequently, research is being conducted to increase the specificity of enediyne toxicity.

Structure and Reactivity
A nine- or ten-membered ring containing a double bond between two triple bonds is termed the warhead of the enediyne. In this state, the warhead is inactive. Enediynes are triggered into a chemically active state via Bergman or Myers-Saito cyclization. The triggering mechanism can be attributed to an intramolecular nucleophilic attack initiated by one of the variable regions of the molecule. Triggering can also occur via attack by an external nucleophile. Bergman cyclization restructures the enediyne ring into two smaller rings. One electron from each of the enediyne triple bonds is pushed to the adjacent single bonds, generating two new double bonds. Meanwhile, another pair of electrons (one from each alkyne) is used form a new covalent bond. The resulting formation is a 1,4-benzenoid diradical fused to a ring comprised of the leftover atoms from the original enediyne.

Some enediynes have an epoxide group attached to their ring, making Bergman cyclization unfavorable due to steric hindrance. For Bergman cyclization to occur, the epoxide must be removed. Myers-Saito cyclization is another triggering mechanism by which an enediyne warhead becomes a diradical. This mechanism requires the alkene of the enediyne to be part of a diene with a double bond in a variable group. A nucleophile will attack the double bond in the variable region, causing a chain reaction of electron pushing. Ultimately, one of the triple bonds of the enediyne is converted to a cumulene. The cumulene and the remaining alkyne donate one electron each to form a new covalent bond.

The diradicals generated by Bergman and Myers-Saito cyclization are highly reactive.

Classes of Enediynes
There are fourteen naturally occurring enediynes. The other existing classes of enediynes have been synthesized in the lab.

Enediynes have been split into two sub-families: those with nine members in the core enediyne ring and those with ten-membered rings.

Nine-Membered Enediyne Rings (Chromoproteins)
The nine-membered enediynes are also referred to as chromoproteins because they have an attached protein as a variable group. This protein is necessary for transport and stabilization of the enediyne group.

Neocarzinostatin
Neocarzinostatin is a natural product of Streptomyces carzinostaticus. It forms an apoprotein with a 113-amino acid polypeptide which can cleave histone protein H1. Neocarzinostatin is an example of an enediyne that undergoes triggering via Myers-Saito cyclization. An analog of neocarzinostatin, SMANCS, has been approved for use in Japan as an antitumor drug for liver cancer.

C-1027
Also known as lidamycin, C-1027 is one of the most potent antitumor enediynes. C-1027 was first isolated from Streptomyces globisporus in a soil sample taken from the Qian-Jiang District of China. Unlike most enediynes, C-1027 does not undergo a triggering process to become an activated 1,4-benzenoid diradical. C-1027 has demonstrated potential efficacy against hypoxic tumors.

Calicheamicins
The calicheamicins are a sub-family of enediynes that were isolated from Micromonospora echinospora calichensis. All calicheamicin family members demonstrate potent antimicrobial activity against Gram-positive and Gram-negative organisms. Calicheamicn γ1 exhibited significant antitumor activity against leukemia and melanoma cells in vivo. The calicheamicins are notably similar in structure to the esperamicins.

Esperamicins
The esperamicins are a sub-family of enediynes that are considered among the most potent antitumor antibiotics discovered. First isolated in Actinomadura verrucosospora, members of the esperamicin family include esperamicin A1, A1b, A2, A3, A4, B1, B2, and X. Esperamicin X is an inactive esperamicin naturally produced by A. verrucosospora. Compounds with thiol groups induce triggering among the esperamicins.

Dynemicins
The dynemicins are a sub-family of enediynes whose members are organic compounds generated in Micromonospora chersina. Dynemicin A was the first member of this sub-family to be discovered. It was isolated from M. chersina in a soil sample taken from the state of Gujarat in India. Dynemicins are violet in color because they contain anthraquinone as a variable group attached to the enediyne core. Dynemycins have demonstrated strong antitumor activity against leukemia and melanoma cells.

Golfomycin A
Golfomycin A is a synthetic enediyne molecule designed in an attempt to create a more easily manufactured antitumor antibiotic. DNA strand-scission induced by golfomycin A is pH dependent. Preliminary in vitro studies have demonstrated that golfomycin A can reduce carcinomas in bladder cells.