Taxine

Taxine is a very toxic [alkaloid] which is found in Yew tree (Taxus baccata). It can also be found in various other taxus species. But the taxus baccata contains the highest taxine concentration. It is present mostly in all parts of the tree but in seeds its concentration is relatively higher. The major constituents of taxine are Taxine A and Taxine B. From the ancient days, these alkaloids has been used as suicidal agent and a chemical weapon during hunting and warfare. Taxine A and Taxine B both are cardiotoxic but taxine B is more potent. IUPAC name of taxine B is - (2alpha,5alpha,9alpha,10beta)-10-Acetoxy-1,2,9-trihydroxy-13-oxotaxa-4(20),11-dien-5-yl (3R)-3-(dimethylamino)-3-phenylpropanoate.

This substance is characterized by high melting and boiling point. Taxine is soluble in chloroform and alcohol, and insoluble in water or oil.

Taxine B is cardiotoxic and has been found to be very potent, and sometimes used as suicidal and war weapons. For taxanes, as this group of derivatives is commonly called, more than 100 have been discovered to date, and these have been extracted from various yew species. Biosynthesis of the anticancer drug Taxol in Taxus (yew) species involves 19 steps from the universal diterpenoid progenitor geranylgeranyl diphosphate derived by the plastidial methyl erythritol phosphate pathway for isoprenoid precursor supply. Following the committed cyclization to the taxane skeleton, eight cytochrome P450-mediated oxygenations, three CoA-dependent acyl/aroyl transfers, an oxidation at C9, and oxetane (D-ring) formation yield the intermediate baccatin III, to which the functionally important C13-side chain is appended in five additional steps.

Taxine B contains normal taxane terpenoid core and has a 13-oxo group. The side chain present in Taxine B is winterstein's acid Taxine B undergoes isomerization to Isotaxine B due to migration of Acetyl group. The migration of Acetyl group and formation of Isotaxine B has been studied, characterized by NMR and Mass spectrometry by H. Kohler et. al. in 2006 Taxine B is used for synthesis of Paclitaxel and 7-deoxypaclitaxel derivatives, which are known for their anticancer activity by stabilizing the microtubules and suppressing the microtubule dynamic

Taxine B is more potent and degree of toxicity depends on the dose. In addition, Taxine can be very rapidly absorbed with in the body so the patient does not give much time before they die if high dose is taken. Taxine B has negative inotropic effect and it delays atrioventricular (AV) conduction. It also acts as a class- I antiarrhythmic drug. Taxine B is LD 50. The following are signs and symptoms of toxicity in animals: Ataxia, Bradycardia, Dyspnea, muscle tremors, Convulsions followed by death. The humans have symptoms such as dizziness, nausea, vomiting, pupil dilation, abdominal pain. These signs may proceed further to bradycardia and death of the patient. Treatment for Taxine B includes rumenotomy in animals and intramuscular doses of Atropine sulfate or Lidocaine. Taxine alkaloids cause fatal poisoning, in particular due to the compound’s toxic effect on the cardiovascular apparatus. In addition, there is no specific antidote for taxine B so the patients can only receive treatment for their symptoms.

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