The Alkaloids Pharmacology

Biomedical Journal of Scientific & Technical Research
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Its leaves are opposite, oblong, with round apex, simple, whole, dark green color, shiny in the upper side, and of short petioles.


Read the latest chapters of The Alkaloids: Chemistry and Pharmacology at, Elsevier's leading platform of peer-reviewed scholarly literature. PDF | Plant alkaloids, one of the largest groups of natural products, represent a highly diverse group of chemical entities. Historically, although.

Its branches can be erect or decumbent, and its relatively big flowers are axillary, solitary, of short peduncle and with five petals. Its fruit is a dehiscent follicle that contains numerous seeds more than 20 of color black [ 19 , 20 ].

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There are several forms differentiated by flower coloration, probably due to genotypic variations, prevailing those of white color, white with red centre, red centre, dark rose almost purple , white with disperse centre to violet rose or with dark centre bordered with red. This species of wild plant can tolerate many types of biotic and abiotic stress.

Vincristine and vinblastine are potent mitotic inhibitors used in leukemia chemotherapy; they are structures hard to synthesize chemically, like other cancer-fighting drugs such as taxol [ 21 ] thus biotechnological approaches represent the best route for its obtention. It has been shown that the biosynthesis of terpenoid indole alkaloids TIA in C.

The Alkaloids: Chemistry and Pharmacology, Volume 30 - 1st Edition

Several studies have dealt with the regulation of some of the genes coding for the enzymes involved in the synthesis of TIA and recently some of the molecular mechanisms controlling gene expression in cell suspension cultures of C. The first step in TIA biosynthesis is the formation of tryptamine [ 24 ] from the l -tryptophane amino acid in a reaction catalyzed by the TDC enzyme. This cytosolic enzyme binds the primary metabolism with the secondary metabolism and its activity is considered as a limiting step, although not the only one, in the control of TIA biosynthesis [ 25 ].

Another limiting step in the biosynthesis is the tryptamine that binds to the secologanin monoterpene, the final product of the biosynthetic route of iridoids, in a reaction catalyzed by the STR1 enzyme. Tryptamine condensation with iridoid glucoside secologanin under the catalysis of the strictosidine synthase STR results in the formation of strictosidine, the central intermediary in the biosynthesis of all types of indole alkaloids [ 26 ]. Subsequently, strictosidine is metabolized through different enzymatic steps, including those catalyzed by D4H and DAT enzymes that lead to the formation of vindoline and catharanthine, the monoterpene alkaloids precursors to vinblastine and vincristine [ 27 ].

The main alkaloids obtained from C. The elimination of the rest of the glucose of strictosidine by SGD leads to an unstable, highly reactive aglucone, that is believed to convert into 4,21 dehydrogeissoschizine. It is believed that the latter is converted into cathenamine by the cathenamine synthase. Cathenamine is then converted into tabersonine through several steps, transforming into vindoline by a six-step sequence [ 28 ]. Gene and enzyme regulation participating in TIA biosynthesis in C. In addition, it has been found that the molecular mechanisms of regulation respond differentially to the presence of elicitors or to conditions of light and hormone stress, among others [ 29 ].

The tdc and str1 transcripts and their respective proteins show high cellular and tissue specificity, for example, they have been detected exclusively in the superior and inferior epidermis of leaves, in stem epidermis, and flower buds [ 30 ]. In cell cultures of C. The expression of these two genes is inhibited by the presence of auxins, although they are induced by elicitation with fungi, yeast extraction, methyl jasmonate MeJa , salicylic acid, and chitosan. These results suggest that the expression of str1 and tdc in cell cultures of C.

The presence of some elements responding to elicitation in the promoter of the tdc gene has been determined. The analysis of the promoter of the str1 gene of C. In other experiments, [ 32 ] showed that the biosynthetic route of jasmonate octadecanoic acid pathway was an integral part of the signal transduction pathway leading to the expression of tdc and str1 genes in cells in suspension of C. The expression of the promoter of the gene str1 in transgenic cellular cultures of C. In a subsequent report, [ 33 ] identified an element of 42 base pairs pb within the pb fragment—the Jasmonate and Elicitor Responsive Element JERE.

The JERE region showed a GCC sequence in the str1 promoter that was necessary and sufficient for gene expression in the treatment with elicitors and jasmonate. The AP2 domain is found exclusively in plant transcription factors and is involved in the regulation of several stress responses. In cell suspension cultures of C.

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ORCA3 coordinately regulates multiple genes, including dxs, tdc, str1, sgd, cpr, and d4h, which code for pathway routes both of primary and secondary metabolism related to TIA formation [ 23 ]. In situ hybridization and immunolocalization studies have showed that d4h and its protein are located in specialized cells laticifers and idioblasts shown in young leaves, stems and flower buds of C.

Both the transcripts of dat gene and its protein are co-located with d4h and D4H in laticifers and idioblasts [ 30 ]. In addition, studies with intact plants and with plantlings have shown that the induction of the mRNA of dat, and DAT activity and accumulation occur preferentially in leaves and cotyledons of etiolated plants treated with light, but they are not present in roots nor in cell suspension cultures, which explains the impossibility of producing vinblastine and vincristine in cell systems.

Vinblastine is a drug used in the elective regime for the metastatic treatment of testicular cancer. The terminal elimination phase for vincristine is reported to be three to four times longer than the one estimated for vinblastine, and the slow elimination of vincristine from the neuronal susceptible tissue suggest that it plays a role in neurotoxicity commonly seen in clinical adjustments with vincristine but not with vinblastine [ 35 ]. It has been reported that vinblastine inhibits a polymorphic cytochrome P in human hepatic microsomes, but the necessary concentrations were higher than those observed in clinical adjustments [ 38 ].

It is recommended that vinblastine and vincristine doses must be reduced in patients with liver disease. Vincristine is conventionally administered intravenously, in adults, with a dose of 1. Sulkes and Collins have commented on the adjustments that can be provided for conventional doses of vincristine and other drugs [ 39 ]. Of particular importance is the possibility that some patients can show a good clinical response and relatively low toxicity in dose regimes involving the cautious use of large quantities of vincristine.

The initial dose of vinblastine for adults is 3. Considering the traditional use against diabetes, C. Nevertheless, although no extract derived from the plant showed sensitivity in that regard, an occasional observation in blood indicated that some leaf-derived extracts accumulated alkaloids, sensibly decreasing the number of white globules, granulocytes in particular.

This finding motivated scientists to carry out in vitro studies with leukemia cells, which lead to the isolation of vinblastine and vincristine in the 60s, among the more than 70 alkaloids of indolic nature that this plant produces. Later, Svodoba in Lilly successfully performed assays in rats with P leukemia, finding that the tumor was sensitive to these extracts. Don is a plant traditionally used by populations in India, South Africa, China, and Malaysia to treat diabetes.

Most of the reports on the antidiabetic activity of this plant have been made using crude extracts [ 39 , 40 , 41 , 42 ]. Soon et al. Four alkaloids—vindoline I, vindolidine II, vindolicine III and vindolinine IV—were isolated and identified from the dichloromethane leaf extract of this plant.

Classification of Alkaloids

Vincristine is employed to treat lymphocytic acute leukemia the most frequent malign hemopathy in childhood , of which several chromosomic alterations with prognostic importance are known. Among them there are the translocation 4;11 and the translocation 9;22 , which are indicators of a bad prognosis, while hyperdiploidy is associated with a good prognosis [ 44 ] and it attacks lymphomas including solid tumors in children. An experiment with different concentrations of sodium chloride in two varieties of Catharanthus var.

Ozcelik et al. Catharoseumine, a monoterpenoid indole alkaloid, has a unique peroxy bridge, which was identified as a potential inhibitor against falcipain-2 protozoa parasites causes of malaria , showing an IC 50 value of 4. Vinblastine and vincristine showed an antiparasitic effect against Trypanosoma , that causes trypanosomiasis in humans, inhibiting its mitosis and affecting its cellular shape in a dose-dependent manner. It was shown in several animal studies, that ethanolic leaf and flowers extracts decreased the levels of glucose in blood.

Hypoglycemic effects are a result of increasing the use of glucose in liver [ 47 ]. The antidiarrhoeic in vivo activity of ethanolic leaf extracts was tested in Wistar rats with beaver oil as an experimental diarrhea inductor agent. Loperamide and atropine were used as standard drugs.

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The antimicrobial activity of leaf extracts was tested against microorganisms such as Pseudomonas , Salmonella , Staphylococcus and thus, these extracts show promissory effects as prophylactic agents in the treatment of many diseases. Ramya et al.

The results indicated that leaf extracts showed a higher antibacterial activity than the extracts prepared from other parts of the Catharanthus plant. Thus, the aqueous extracts of leaves, stems, roots and flowers showed low microorganism growth [ 52 ] tested leaf extracts of Catharanthus var. Stem extracts of var. This site uses Akismet to reduce spam.

2] Heterocyclic Alkaloids or Typical Alkaloids:

Learn how your comment data is processed. You can read more about what information we collect and how we use your information on our Privacy Policy page. Table below shows the chemical structure and biological significance of these compounds: Name Structure Biological Significance Ephedrine Adrenergic agent-used for asthma and hay fever Colchicine Relieves gout Erythromycin Antibiotic Taxol Paclitaxel Used in the treatment of ovarian cancer, breast cancer and non-small cell lung cancer 2] Heterocyclic Alkaloids or Typical Alkaloids: Structurally these have the nitrogen as a part of a cyclic ring system.

Heterocycle Example 1. Pyrrole and Pyrrolidine Hygrine, Stachydrine 2. Pyrrolizidine Senecionine, Symphitine, Echimidine, Seneciphylline 3. Quinoline Quinine, Quinidine, Cinchonine, Cinchonidine 6. Quinolizidine Lupanine, Cytisine, Laburnine, Sparteine 9. Indolizidine Castanospermine, Swainsonine Imidazole or glyoxaline Pilocarpine, Pilosine Other methods of classification of alkaloids include: Based on their pharmacological action: Alkaloids have very diverse pharmacological actions.

They are known to be adrenergics, antibiotics, poisons, stimulants, diuretics, astringents, anti-inflammatory, anti-hypertensives, anti-mydriatics, analgesics, anti-gout, expectorant, emetic, anti-spasmodic and many others.

1.1 Therapeutic efficacy of BBR in AD

Chemical Information Review Document for Vinpocetine. J Knowl Manag Pract. Int J Clin Exp Med. PIP also exerts persuasive anti-depressant action which is beneficial in case of PD [ 50 , 51 ]. There are several side effects which are linked with the use of high dose of piperine including nausea, vomiting, diarrhea, headaches and dizziness [ ]. Matrine, oxymatrine, allomatridine [67] [70] [71]. Five subtypes M1-M5 of muscarinic receptor are widely distributed in the CNS which are chiefly involved in a vast variety of functions including nociception, cognition and movement regulation [ ].

However, structurally diverse molecules may show similar pharmacological actions while in certain cases the activity might be identical for specific structure. Hence it is very difficult to classify them on the sole basis of pharmacological action. Based on their biosynthetic origin: Biosynthetic origin here means from which fundamental chemical building block these alkaloids are derived.

For example indole alkaloids often come from tryptophan, pyrrolidine and tropane containing alkaloids come from proline and ornithine, quinolizidine containing alkaloids are derived from lysine.