Alkaloids inhibition

The periwinkle, or vinca plant, served as a source for the drugs vincristine and vinblastine, which are commonly referred to as the vinca alkaloids. The vinca alkaloids inhibit the assembly... 

This benzylisoquinoline alkaloid inhibits in vitro the specific bonding of [3H] dopamine to dopamine receptors and abrogates amphetamine-induced circling behavior in rodents with unilateral degeneration of dopaminergic neurons in the corpus striatum (109). 

Vinblastine -vinca alkaloid inhibits tubulin polymerization G2 phase specific -bone marrow suppression -vesicant if extravasated -nausea and vomiting -constipation (often secondary to neuropathy induced ileus) -neuropathy (jaw pain, peripheral neuropathy, autonomic neuropathy) -SIADH -tumor pain... 

Although it is comparatively easy to explain the fact that some alkaloids inhibit AChE because of their molecular features, it is not easy to correlate chemical structure and activity for some other phytochemical types for which AChE inhibition has recently been reported. 

Rahman AU, Khalid A, Sultana N, et al., New natural cholinesterase inhibiting and calcium channel blocking quinoline alkaloids, Inhibition Med Chem 21 703-710, 2006. 

In 2000, Boyd et al. reported for the first time an anti-HIV active carbazole alkaloid, siamenol (89) (see Scheme 2.17). This prenylated carbazole alkaloid inhibited HIV-1 induced cytopathic inhibitor activity in an XTT-tetrazolium assay with EC50 2.6 pg/mL (85,449). Recently, Kongkathip et al. reported anti-HIV-1 activity for O-methylmukonal (glycosinine) (38) (see Scheme 2.9), 7-methoxy-O-methylmu-konal (2,7-dimethoxy-3-formylcarbazole) (48) (see Scheme 2.10), and clausine K (clausazoline-J) (51). These studies showed strong anti-HIV-1 activity for... 

Gocze, P. M., and D. A. Freeman. Cytotoxic effects of cigarette smoke alkaloids inhibit the progesterone production and cell growth of cultured MA-10 Leydig tumor cells. Eur J Obstet Gynecol Reprod Biol 2000, 93(1) 77-83. 

As representative of the derivatives of pyridoacridine, eilatin, a marine alkaloid inhibits in vitro cell proliferation in chronic myeloid leukemia patients [244], Other members of the pyridoacridines, such as alkaloids isolated from a Cystodytes sp. ascidian, inhibit topoisomerase II [245], Additionally, analogues derivatives of these type of alkaloids showed interesting anti-HIV activity [246],... 

This selection of alkaloid activities, though far from complete, clearly shows that many alkaloids inhibit central processes at the cellular, organ, or organismal level, an important requisite for a chemical defense compound. However, most of the potential targets for the 10,000 alkaloids known at present remain to be established. If no activity has been reported, it often means that nobody looked into this question scientifically, and not that a particular alkaloid is without a certain biological property. 

Two new polycyclic guanidine alkaloids, cambrescidins 826 and dehydroaranobine A, were isolated from the marine sponge Monanchora spp. [61]. The pentacyclic guanidine alkaloids inhibit HIV-1 envelope-... 

In the 1990s, it was found that tylophorine alkaloids inhibit several key targets for clinically important anticancer drugs, including the metabolic enzymes thymidylate synthase (TS) and dihydrofolate reductase [8, 94], TS catalyzes the reductive methylation of the substrate dUMP (2 -deoxyuridine 5 -monophosphate) to dTMP (2 -deoxythymidine 5 -monophosphate thymidylate) with concomitant conversion of the cofactor CH2THF (5,10-methylenetetrahydrofolate) to DHF (7,8-dihydrofolate) (see Equation 1). 

The mechanism of human toxicity has not been clearly delineated. In animal models, solanaceous alkaloids inhibit cholinesterase activity and demonstrate cardiac glycoside activity. Solanine inhibits hepatic microsomal enzymes and can cause hemolysis. 

The anti-inflammatory and antiallergic effects of aromoline were evaluated via the measurement of antigen-induced histamine release from leukocytes, and it was found that the alkaloid inhibited antigen-induced histamine release [180]. 

Treatment with berbamine was found to relax K+-precontracted rat aortal rings, with an ICJ0 of about 20 pmol/liter. This relaxation was not inhibited by denudation of the endothelium or by premedication of the aortas with indomethacin, methylene blue or propranolol. In addition, the alkaloid inhibited contractions induced by norepinephrine, phenylephrine, and serotonin in a non-competitive manner, as well as competitively blocking calcium-induced contraction in a Ca+2-free depolarizing PSS. The blockade of calcium entry appears to be the major mechanism of the dilatory effect of this alkaloid, but its interaction with a-adrenoceptors was not excluded [188]. 

Intraperitoneal administration of coptisine at dosages of 0.5, 1, and 5 mg/kg/day to original-type anti-GBM-induced nephritic rats was shown to be effective in the inhibition of urinary protein excretion, elevation of serum cholesterol, and creatinine contents, as well glomerular histopathological changes. The alkaloid inhibited platelet aggregation in both in vitro and in vivo assays. These results suggest that the antinephritic effect of coptisine may be due partly to antiplatelet action and improved renal hemodynamics, via the alteration of prostanoid synthesis [223]. 

The Catharanthus-alkaloids inhibit mitosis, binding to the nucleus protein tubulin in... 

These alkaloids inhibit melanin biosynthesis in B16 melanoma cells this represents a rare example of such inhibition by indole alkaloids. 

For this purpose we have determined whether an alkaloid can displace a specifically bound ligand from a neuroreceptor, such as ot, 0t2 adrenergic receptors, serotonin receptor [5-HT2], and nicotinic and muscarinic acetyl choline receptors (Table 15) obtained from porcine brains [69-72]. In addition, we have determined whether the same alkaloids inhibit acetylcholine esterase, whether they intercalate DNA, inhibit DNA polymerase I, reverse transcriptase, protein biosynthesis and membrane stability [40, 73]. The results can be summarized as follows ... 

Antiplatelet Aggregation Activity. Alkaloids from Annonaceous plants were reported to inhibit platelet aggregation. According to our previous studies, more than twenty compounds were examined and most of the alkaloids were found inhibiting arachidonic acid (A.A) induced platelet aggregation [41]. Phenanthrene-alkaloids inhibited platelet aggregation initiated by four inducers (arachidonic acid, PAF, collagen, and thrombine)... 

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