vinca alkaloids

Summary

Summary: A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.

Top Publications

  1. Feher G, Koltai K, Kesmarky G, Horvath B, Toth K, Komoly S, et al. Effect of parenteral or oral vinpocetine on the hemorheological parameters of patients with chronic cerebrovascular diseases. Phytomedicine. 2009;16:111-7 pubmed publisher
    ..Our results confirmed the beneficial rheological effects of high-dose parenteral VP (partially caused by hemodilution) observed previously, and also warrant its long-term oral admission to maintain the beneficial rheological changes. ..
  2. Kémeny V, Molnar S, Andrejkovics M, Makai A, Csiba L. Acute and chronic effects of vinpocetine on cerebral hemodynamics and neuropsychological performance in multi-infarct patients. J Clin Pharmacol. 2005;45:1048-54 pubmed
    ..No other significant differences in the neuropsychological test could be detected between the treatment and the placebo groups. Longer lasting and higher dosage of vinpocetine therapy is suggested to prove its potential effect. ..
  3. Szczepanik A, Sikorska A, Slomkowski M, Konopka L. The use of vinca alkaloids in preparation for splenectomy of corticosteroid refractory chronic immune thrombocytopenic purpura patients. Int J Lab Hematol. 2007;29:347-51 pubmed
    Administration of vinca alkaloids (VA) to chronic corticosteroid refractory immune thrombocytopenia (ITP) patients results in a temporary increase of platelet count...
  4. Abdel Salam O, Oraby F, Hassan N. Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats. Acta Biol Hung. 2007;58:411-9 pubmed publisher
    ..2 mg/kg of vinpocetine was similar to that obtained by 30 mg/kg silymarin. Therefore, it is suggested that vinpocetine might be a good pharmacological agent in the treatment of liver disease besides its neuroprotective effects. ..
  5. Duflos A, Kruczynski A, Barret J. Novel aspects of natural and modified vinca alkaloids. Curr Med Chem Anticancer Agents. 2002;2:55-70 pubmed
    The clinical interest of Vinca alkaloids was clearly identified as early as 1965 and so this class of compounds has been used as anticancer agents for more than 30 years...
  6. Gerasimenko I, Sheludko Y, Ma X, Stockigt J. Heterologous expression of a Rauvolfia cDNA encoding strictosidine glucosidase, a biosynthetic key to over 2000 monoterpenoid indole alkaloids. Eur J Biochem. 2002;269:2204-13 pubmed
    ..serpentina and C. roseus cell suspension cultures occurs at a later stage than strictosidine deglucosylation. ..
  7. Fahy J. Modifications in the "upper" velbenamine part of the Vinca alkaloids have major implications for tubulin interacting activities. Curr Pharm Des. 2001;7:1181-97 pubmed
    b>Vinca alkaloids represent a chemical class of major interest in cancer chemotherapy. The lead compounds vinblastine and vincristine have been employed in clinical practice for more than thirty years and remain widely used to this day...
  8. Ngan V, Bellman K, Hill B, Wilson L, Jordan M. Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine. Mol Pharmacol. 2001;60:225-32 pubmed
    The two second-generation Vinca alkaloids, vinorelbine and vinflunine, affect microtubule dynamics very differently from vinblastine, a first generation Vinca alkaloid...
  9. Spagnuolo P, Hu J, Hurren R, Wang X, Gronda M, Sukhai M, et al. The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma. Blood. 2010;115:4824-33 pubmed publisher
    ..Therefore, flubendazole is a novel microtubule inhibitor that displays preclinical activity in leukemia and myeloma. ..

More Information

Publications62

  1. Chiu W, Luo S, Chen C, Cheng J, Hsieh C, Wang C, et al. Vinca alkaloids cause aberrant ROS-mediated JNK activation, Mcl-1 downregulation, DNA damage, mitochondrial dysfunction, and apoptosis in lung adenocarcinoma cells. Biochem Pharmacol. 2012;83:1159-71 pubmed publisher
    b>Vinca alkaloids are clinically used to inhibit the growth of malignancy by interfering with microtubule polymerization...
  2. Deshmukh R, Sharma V, Mehan S, Sharma N, Bedi K. Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine -- a PDE1 inhibitor. Eur J Pharmacol. 2009;620:49-56 pubmed publisher
    ..The observed beneficial effects of vinpocetine on spatial memory may be due to its ability to favorably modulate cholinergic functions, prevent neuronal cell damage and possibly through its antioxidant mechanism also. ..
  3. Sertel S, Fu Y, Zu Y, Rebacz B, Konkimalla B, Plinkert P, et al. Molecular docking and pharmacogenomics of vinca alkaloids and their monomeric precursors, vindoline and catharanthine. Biochem Pharmacol. 2011;81:723-35 pubmed publisher
    ..In addition to tubulin as primary target, microarray-based mRNA signatures of responsiveness of these compounds have been identified by COMPARE and signaling pathway profiling. ..
  4. Zhou H, Tai Y, Sun C, Pan Y. Rapid identification of vinca alkaloids by direct-injection electrospray ionisation tandem mass spectrometry and confirmation by high-performance liquid chromatography-mass spectrometry. Phytochem Anal. 2005;16:328-33 pubmed
    A simple and rapid method for the identification of Vinca alkaloids from a crude extract of Catharanthus roseus G...
  5. Barthe L, Ribet J, Pélissou M, Degude M, Fahy J, Duflos A. Optimization of the separation of Vinca alkaloids by nonaqueous capillary electrophoresis. J Chromatogr A. 2002;968:241-50 pubmed
    A rapid method for the determination of Vinca alkaloids by nonaqueous capillary electrophoresis with diode array detection has been developed...
  6. Ehrhardt H, Schrembs D, Moritz C, Wachter F, Haldar S, Graubner U, et al. Optimized anti-tumor effects of anthracyclines plus Vinca alkaloids using a novel, mechanism-based application schedule. Blood. 2011;118:6123-31 pubmed publisher
    Application of anthracyclines and Vinca alkaloids on the same day represents a hallmark of polychemotherapy protocols for hematopoietic malignancies...
  7. Valikovics A. [Investigation of the effect of vinpocetine on cerebral blood flow and cognitive functions]. Ideggyogy Sz. 2007;60:301-10 pubmed
    ..The authors recommend the use of vinpocetine for the treatment of patients with mild cognitive impairment. ..
  8. Coderch C, Morreale A, Gago F. Tubulin-based structure-affinity relationships for antimitotic Vinca alkaloids. Anticancer Agents Med Chem. 2012;12:219-25 pubmed
    The Vinca alkaloids are a group of widely used anticancer drugs, originally extracted from the Madagascar periwinkle, that disrupt microtubule dynamics in mammalian cells by interfering with proper assembly of ?,?-tubulin heterodimers...
  9. Murata J, Roepke J, Gordon H, De Luca V. The leaf epidermome of Catharanthus roseus reveals its biochemical specialization. Plant Cell. 2008;20:524-42 pubmed publisher
    ..The value and versatility of this EST data set for biochemical and biological analysis of leaf epidermal cells is also discussed. ..
  10. Verissimo C, Cheng S, Puigvert J, Qin Y, Vroon A, van Deutekom J, et al. Combining doublecortin-like kinase silencing and vinca alkaloids results in a synergistic apoptotic effect in neuroblastoma cells. J Pharmacol Exp Ther. 2012;342:119-30 pubmed publisher
    Microtubule-destabilizing agents, such as vinca alkaloids (VAs), are part of the treatment currently applied in patients with high-risk neuroblastoma (NB)...
  11. Barleben L, Panjikar S, Ruppert M, Koepke J, Stockigt J. Molecular architecture of strictosidine glucosidase: the gateway to the biosynthesis of the monoterpenoid indole alkaloid family. Plant Cell. 2007;19:2886-97 pubmed
    ..The data presented here will contribute to deciphering the structure and reaction mechanism of other higher plant glucosidases. ..
  12. Edler M, Fernandez A, Lassota P, Ireland C, Barrows L. Inhibition of tubulin polymerization by vitilevuamide, a bicyclic marine peptide, at a site distinct from colchicine, the vinca alkaloids, and dolastatin 10. Biochem Pharmacol. 2002;63:707-15 pubmed
    ..GTP binding was also found to be weakly affected by the presence of vitilevuamide. These results suggest the possibility that vitilevuamide inhibits tubulin polymerization via an interaction at a unique site. ..
  13. Medina A, Krahe T, Ramoa A. Restoration of neuronal plasticity by a phosphodiesterase type 1 inhibitor in a model of fetal alcohol exposure. J Neurosci. 2006;26:1057-60 pubmed
    ..Our finding should contribute to a better understanding and treatment of cognitive deficits associated with mental disorders, such as FAS. ..
  14. Tárnok K, Kiss E, Luiten P, Nyakas C, Tihanyi K, Schlett K, et al. Effects of Vinpocetine on mitochondrial function and neuroprotection in primary cortical neurons. Neurochem Int. 2008;53:289-95 pubmed publisher
    ..In summary, the present results indicate that the neuroprotective action of vinpocetine in culture can not be explained by its effect on neuronal PBRs alone and that additional drug targets are involved. ..
  15. Gan P, Kavallaris M. Tubulin-targeted drug action: functional significance of class ii and class IVb beta-tubulin in vinca alkaloid sensitivity. Cancer Res. 2008;68:9817-24 pubmed publisher
    ..RNA-mediated knockdown of either betaII- or betaIVb-tubulin hypersensitized the lung cancer cell lines to Vinca alkaloids, with the effects more pronounced following betaIVb-tubulin knockdown...
  16. Banner K, Page C. Acute versus chronic administration of phosphodiesterase inhibitors on allergen-induced pulmonary cell influx in sensitized guinea-pigs. Br J Pharmacol. 1995;114:93-8 pubmed
  17. Bereczki D, Fekete I. A systematic review of vinpocetine therapy in acute ischaemic stroke. Eur J Clin Pharmacol. 1999;55:349-52 pubmed
    ..Based on only one small randomised controlled unconfounded study, presently there is not enough evidence to decide whether the administration of vinpocetine does or does not decrease case fatality and dependency in acute stroke. ..
  18. Vázquez Flota F, Carrillo Pech M, Minero García Y, de Lourdes Miranda Ham M. Alkaloid metabolism in wounded Catharanthus roseus seedlings. Plant Physiol Biochem. 2004;42:623-8 pubmed
    ..No synergistic or additive effects were observed when wounded seedlings were exposed to ethylene or jasmonate. ..
  19. Kim R, Osaki A, Hirai T, Toge T. Utility of technetium-99m methoxyisobutyl isonitrile uptake analysis for prediction of the response to chemotherapy in advanced and relapsed breast cancer. Breast Cancer. 2002;9:240-7 pubmed
    ..effectiveness of Tc-SESTAMIBI for predicting the chemotherapy response to treatment with anthracyclines and vinca alkaloids, we retrospectively evaluated the relationship between the accumulation of Tc-SESTAMIBI and the tumor ..
  20. Takuma K, Lee E, Enomoto R, Mori K, Baba A, Matsuda T. Ibudilast attenuates astrocyte apoptosis via cyclic GMP signalling pathway in an in vitro reperfusion model. Br J Pharmacol. 2001;133:841-8 pubmed
    ..These findings suggest that ibudilast prevents the H(2)O(2)-induced delayed apoptosis of astrocytes via a cyclic GMP, but not cyclic AMP, signalling pathway. ..
  21. Chen Q, Li N, Zhang W, Chen J, Chen Z. Simultaneous determination of vinblastine and its monomeric precursors vindoline and catharanthine in Catharanthus roseus by capillary electrophoresis-mass spectrometry. J Sep Sci. 2011;34:2885-92 pubmed publisher
    ..1 ?g/mL, respectively. The precision was not more than 4.54% and the mean recovery of the analytes was 95.04-97.04%. The CE-MS method was successfully applied to determine VLB and its monomeric precursors in real sample C. roseus. ..
  22. Parissenti A, Hembruff S, Villeneuve D, Veitch Z, Guo B, Eng J. Gene expression profiles as biomarkers for the prediction of chemotherapy drug response in human tumour cells. Anticancer Drugs. 2007;18:499-523 pubmed
    ..Genetic predictors of response to a variety of anticancer agents are discussed, including the anthracyclines, taxanes, topoisomerase I and II inhibitors, nucleoside analogs, alkylating agents, and vinca alkaloids.
  23. Atsumi S, Nagasawa A, Koyano T, Kowithayakornd T, Umezawa K. Suppression of TGF-beta signaling by conophylline via upregulation of c-Jun expression. Cell Mol Life Sci. 2003;60:2516-25 pubmed
    ..Thus, our data suggest that inhibition of TGF-beta-induced promoter activity by conophylline can be attributed to its potency in modulating the interaction of downstream transcriptional factors via upregulation of c-Jun expression. ..
  24. Ramani S, Chelliah J. UV-B-induced signaling events leading to enhanced-production of catharanthine in Catharanthus roseus cell suspension cultures. BMC Plant Biol. 2007;7:61 pubmed
    ..roseus cell suspension cultures. Based on these findings, a model for signal transduction cascade has been proposed. ..
  25. Cui S, Nie S, Li L, Wang C, Pan W, Sun J. Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine. Drug Dev Ind Pharm. 2009;35:603-11 pubmed publisher
    ..These results obtained demonstrated that vinpocetine absorption was enhanced significantly by employing SMEDDS. Therefore, SMEDDS might provide an efficient way of improving oral bioavailability of poorly water-soluble drugs. ..
  26. Lantz C, Wang W, Medina A. Early alcohol exposure disrupts visual cortex plasticity in mice. Int J Dev Neurosci. 2012;30:351-7 pubmed publisher
    ..Our findings suggest that the combined activation of the cAMP and cGMP cascades may be a good approach to improve neuronal plasticity in FASD models. ..
  27. England D, Padwa A. General access to the vinca and tacaman alkaloids using a Rh(II)-catalyzed cyclization/cycloaddition cascade. J Org Chem. 2008;73:2792-802 pubmed publisher
    ..A variation of the cascade sequence of reactions used to synthesize (+/-)-3H-epivincamine was also employed for the synthesis of the tacaman alkaloids (+/-)-tacamonine and (+/-)-apotacamine. ..
  28. Szapary L, Kesmarky G, Toth K, Misnyovszky M, Tóth T, Balogh A, et al. [Vinpocetin in neurological diseases]. Ideggyogy Sz. 2012;65:387-93 pubmed
    ..Based on the above mentioned results, vinpocetin plays an important role both in basic research and in clinical management of different neurological diseases. ..
  29. Damen C, Rosing H, Schellens J, Beijnen J. High-performance liquid chromatography coupled with mass spectrometry for the quantitative analysis of vinca-alkaloids in biological matrices: a concise survey from the literature. Biomed Chromatogr. 2010;24:83-90 pubmed publisher
    ..These problems encounter carry-over and absorption effects and solutions will be provided how to circumvent these problems. ..
  30. Erdo S, Molnar P, Lakics V, Bence J, Tomoskozi Z. Vincamine and vincanol are potent blockers of voltage-gated Na+ channels. Eur J Pharmacol. 1996;314:69-73 pubmed
    ..The present findings indicate that the three vinca derivatives are potent blockers of voltage-gated Na+ channels, a mechanism that may contribute at least in part to the pharmacological/therapeutic benefit of these drugs. ..
  31. Drago F, Grassi M, Valerio C, Spadaro F, D Agata V, Lauria N. Effects of vinburnine on experimental models of learning and memory impairments. Pharmacol Biochem Behav. 1990;37:53-7 pubmed
    ..In particular, as scopolamine acts as anticholinergic drug, it is possible that VNB mechanism of action includes also a stimulation of acetylcholine neurotransmission. ..
  32. Dézsi L, Kis Varga I, Nagy J, Komlódi Z, Kárpáti E. [Neuroprotective effects of vinpocetine in vivo and in vitro. Apovincaminic acid derivatives as potential therapeutic tools in ischemic stroke]. Acta Pharm Hung. 2002;72:84-91 pubmed
    ..These results together with former literature data indicate that apovincaminic acid derivatives possessing strong neuroprotective potential may play an important role in the therapy of ischemic stroke. ..
  33. Jordan M. Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr Med Chem Anticancer Agents. 2002;2:1-17 pubmed
    ..These drugs include several that inhibit microtubule polymerization at high drug concentrations, namely, the Vinca alkaloids, cryptophycins, halichondrins, estramustine, and colchicine...
  34. Zhang D, Song H, Qin Y. Total synthesis of indoline alkaloids: A cyclopropanation strategy. Acc Chem Res. 2011;44:447-57 pubmed publisher
    ..The observation of a retro Diels-Alder reaction during our synthesis of communesin F inspired the hetero Diels-Alder reaction on which our total synthesis of perophoramidine was based. ..
  35. Ogata T, Li L, Yamada S, Yamamoto Y, Tanaka Y, Takei I, et al. Promotion of beta-cell differentiation by conophylline in fetal and neonatal rat pancreas. Diabetes. 2004;53:2596-602 pubmed
    ..These results suggest that conophylline induces differentiation of pancreatic precursor cells and increases the formation of beta-cells. ..
  36. Truss M, Stief C, Uckert S, Becker A, Schultheiss D, Machtens S, et al. Initial clinical experience with the selective phosphodiesterase-I isoenzyme inhibitor vinpocetine in the treatment of urge incontinence and low compliance bladder. World J Urol. 2000;18:439-43 pubmed
    ..Although these initial data are preliminary, they represent the first evidence that isoenzyme-selective PDE inhibition may be a novel approach to the treatment of lower urinary tract disorders. ..
  37. Horvath S. [The use of vinpocetine in chronic disorders caused by cerebral hypoperfusion]. Orv Hetil. 2001;142:383-9 pubmed
    ..This fact might give an explanation on the beneficial effect of vinpocetine on clinical signs and symptoms of chronic cerebrovascular insufficiency. ..
  38. Cormier A, Knossow M, Wang C, Gigant B. The binding of vinca domain agents to tubulin: structural and biochemical studies. Methods Cell Biol. 2010;95:373-90 pubmed publisher
    ..In addition, these studies have provided new information on the interaction of tubulin with guanine nucleotides, namely on the mechanisms of nucleotide exchange and hydrolysis. ..
  39. Gulcin I, Beydemir S, Topal F, Gagua N, Bakuridze A, Bayram R, et al. Apoptotic, antioxidant and antiradical effects of majdine and isomajdine from Vinca herbacea Waldst. and kit. J Enzyme Inhib Med Chem. 2012;27:587-94 pubmed publisher
    ..On the other hand, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ?-tocopherol and trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) were used as reference antioxidants. ..
  40. Kuehne M, Qin Y, Huot A, Bane S. The syntheses of 16a'-homo-leurosidine and 16a'-homo-vinblastine. Generation of atropisomers. J Org Chem. 2001;66:5317-28 pubmed
    ..The synthesis was achieved through a stereoselective inversion of the tertiary hydroxyl function in the enantioselectively generated C-20' progenitor 39. ..
  41. Verma A, Laakso I, Seppanen Laakso T, Huhtikangas A, Riekkola M. A simplified procedure for indole alkaloid extraction from Catharanthus roseus combined with a semi-synthetic production process for vinblastine. Molecules. 2007;12:1307-15 pubmed
    ..The mass spectra of vinblastine were dominated by the corresponding protonated molecular ion [M+H]+ at m/z 811 and the characteristic fragment ions matched with those of the standard compound. ..
  42. Nekrassov V, Sitges M. Vinpocetine inhibits the epileptic cortical activity and auditory alterations induced by pentylenetetrazole in the guinea pig in vivo. Epilepsy Res. 2004;60:63-71 pubmed
    ..These results show the antiepileptic potential of vinpocetine and indicate the capability of vinpocetine to prevent the changes in the BAEP waves associated with the hearing loss observed during generalized epilepsy. ..
  43. Liaw T, Chang M, Kavallaris M. The cytoskeleton as a therapeutic target in childhood acute leukemia: obstacles and opportunities. Curr Drug Targets. 2007;8:739-49 pubmed
    ..Natural product tubulin-binding agents such as the Vinca alkaloids have proven highly effective in the treatment of leukemia...
  44. Ribeiro L, Carvalho R, Ferreira D, Veiga F. Multicomponent complex formation between vinpocetine, cyclodextrins, tartaric acid and water-soluble polymers monitored by NMR and solubility studies. Eur J Pharm Sci. 2005;24:1-13 pubmed
  45. Kaneda T, Watanabe A, Shimizu K, Urakawa N, Nakajyo S. Effects of various selective phosphodiesterase inhibitors on carbachol-induced contraction and cyclic nucleotide contents in the guinea pig gall bladder. J Vet Med Sci. 2005;67:659-65 pubmed
    ..In conclusion, the effect of PDE inhibitors in the guinea pig gall bladder was different from those in smooth muscles, such as the trachea, taenia coli, and aorta. ..
  46. Nakade Y, Sakamoto K, Yamauchi T, Inoue T, Kobayashi Y, Yamamoto T, et al. Conophylline inhibits non-alcoholic steatohepatitis in mice. PLoS ONE. 2017;12:e0178436 pubmed publisher
    ..CnP might accordingly be a suitable therapeutic option for NASH. ..
  47. Li H, Boonnak N, Padwa A. N-alkenyl indoles as useful intermediates for alkaloid synthesis. J Org Chem. 2011;76:9488-96 pubmed publisher
    ..The work described provides an attractive route to the tetracyclic core of some vinca alkaloids, including the tetrahydroisoquinocarbazole RS-2135.
  48. Giovanelli E, Leroux S, Moisan L, Carreyre H, Thuery P, Buisson D, et al. On the elucidation of the mechanism of Vinca alkaloid fluorination in superacidic medium. Org Lett. 2011;13:4116-9 pubmed publisher
    Detailed investigations on one of the key steps of the superacidic fluorination of Vinca alkaloids that is the origin of C20' activation are reported...
  49. Gabryel B, Adamek M, Pudełko A, Małecki A, Trzeciak H. Piracetam and vinpocetine exert cytoprotective activity and prevent apoptosis of astrocytes in vitro in hypoxia and reoxygenation. Neurotoxicology. 2002;23:19-31 pubmed
    ..The higher concentration of VINP (10 microM) was detrimental in hypoxic conditions. Our experiment proved the significant cytoprotective effect of 1 mM PIR and 0.1 microM VINP on astrocytes in vitro. ..
  50. Rotella D. American Chemical Society--236th National Meeting & Exposition. Drug development for tuberculosis and cancer. IDrugs. 2008;11:699-701 pubmed
  51. Stockigt J, Barleben L, Panjikar S, Loris E. 3D-Structure and function of strictosidine synthase--the key enzyme of monoterpenoid indole alkaloid biosynthesis. Plant Physiol Biochem. 2008;46:340-55 pubmed publisher
    ..Finally, alignment studies of functionally expressed strictosidine synthases are presented and the evolutionary aspects of sequence- and structure-related beta-propeller folds are discussed. ..
  52. Szapary L, Horvath B, Alexy T, Marton Z, Kesmarky G, Szots M, et al. [Effect of vinpocetin on the hemorheologic parameters in patients with chronic cerebrovascular disease]. Orv Hetil. 2003;144:973-8 pubmed
    ..The beneficial rheological effect of high dose parenteral vinpocetine indicates the use of this drug in the treatment of chronic cerebrovascular diseases. ..
  53. Vas A, Gulyas B. Eburnamine derivatives and the brain. Med Res Rev. 2005;25:737-57 pubmed
    ..Vinpocetine exerts beneficial effects in cerebral glucose metabolism and regional cerebral blood flow in chronic post-stroke patients. ..