Kumarin

Kumarin (2H-chromene-2one ya 2H-1-benzopyranon-2) - lactone o-hydroxycinnamic turşusu.

Xüsusiyyətləri

Yeni kəsilmiş otların qoxusunu verən rəngsiz kristallardır; ərimə temperaturu 70 ° C, qaynama temperaturu 291 ° C-dir. Kumarin spirt və efirdə yaxşı, suda zəif həll olur ,4-hidroksillə yüngül turşu xassəsi göstərdiyi üçün, bir qədər qələvi mühitdə həll edilə bilər.

Kimyəvi xassələr

Kumarin benzoldan fərqli olaraq doymamış laktonlar və ya benzoləvəzləyicilərlə daha az reaksiya qabiliyyətinə malikdir. A

Təbiətdə olması

Kumarin glikosidlər şəklində bir çox bitkilərin tərkibində aşkar edilmişdir - onların nümayəndələri arasında Astrov ailə ( gerbera, chamomile, civanperçemi ), eləcə də yonca, bizon, darçını göstərmək olar.

Alınması

Sənayedə coumarin salisilik aldehid və asatik anhidritdən əldə edilir (bax) Perkin reaksiya ).

Tətbiqi

Kumarindən tütün məhsullarının istehsalında və ətir sənayesində istifadə olunur. tTörəmələridən (coumarins) boya lazerlərində istifadə olunur. Qalvanika sənayesində də güclü parlayıcı kimi istifadə olunur. Kumarinin bir insana fizioloji təsiri çox zəifdir. Bununla birlikdə, coumarin müxtəlif bitkilər üzərində nəzərə çarpacaq dərəcədə təsir göstərir. Koumarin törəmələrində fizioloji təsiri daha qabarıqdır. Məsələn, coumarin-3-karboksilik turşusu törəmələri hipnotikdir. Dikumarol (3,3'-metilen-bis-4-hidroksikumarin) qan laxtalanmasına müdaxilə edir.

Mənbə

• Химическая энциклопедия / Редкол.: Кнунянц И.Л. и др.. — М.: Советская энциклопедия, 1990. — Т. 2 (Даф-Мед). — 671 с. — ISBN 5-82270-035-5.
• Lake B.G. Coumarin metabolism toxicity and carcinogenicity: relevance for human risk assessment / B.G. Lake // Food and Chemical Toxicology. –1999. –№ 37. –Р. 423–453.
• Carlton B. D. Effects of Coumarin Following Perinatal and Chronic Exposure in SpragueWDawley Rats and CDW1 Mice / B. D. Carlton, J.–C. Auburn, G. S. Simon //Fundamental and Applied Toxicology. W1996. – № 30. –P. 145–151.
• Opdyke D. L. J. Monographs on fragrance raw materials: coumarin/ D. L. J. Opdyke// Food and cosmetics Toxicology . –1974. –№ 12. –P. 385–388.
• Качественное обнаружение кумаринов в растительном сырье / Г.А. Дрозд, Н.Ф. Комиссаренко // IV Всесоюзный симпоз. по фенольным соединениям. –Ташкент. –1982. –С. 27–28.
• The pharmacology, metabolism, analysis and applications of coumarin and coumarinWrelated compounds / D. Egan, R. O'Kennedy, E. Moran [et al.] // Drug. Metab. Rev. 1990. –№ 22. –P. 503–529.
• Phase II study of coumarin and cimetidine in patients with metastatic renal cell сarcinoma / F. H. Dexeus, С. J. Logothetis, F. Sella, A. [et al.] // J. Clin. Oncol. 1990. –№ 8. –P. 325–329.
• Cox D. The relevancy of liver toxicity in patients treated with coumarin (1,2WbenzoWpyron) / D.Cox, R. O'Kennedy, R. D. Thornes // Hum. Toxicol..–1989. –№
• –P. 501–506. 8. Morris L. SideWeffects of coumarin / L .Morris, P.D.Welsby // Postgrad. Med. J. –1995. –№ 71. – P. 701–702.
• Toxicity of coumarin / L. W. Hazleton, T. W. Tusing, , Zeitlin M.K. [et al.] // J. Pharmacol. Exp. Ther. –1956. –№ 118. –P. 348–358.
• Cohen A.J. Critical review of the toxicology of coumarin with special references to interspecies differW ences in metabolism and hepatotoxic response and their significance to man / A. J. Cohen // Food Chem. Toxicol. –1979. –№ 17. –P. 277–289.
• Lake B. G. Investigations into the mechanism of coumarinWinduced hepatotoxicity in the rat / B. G. Lake // Arch. Toxicol. Suppl. –1984. –№ 7. –P. 16–29.
• Lake B. G. Effect of pretreatment with some mixedWfunction oxidase enzyme inducers on the acute hepatotoxicity of coumarin in the rat / B. G. Lake, J. G. Evans, // Food Chem. Toxicol. –1993. –№ 31. – P. 963–970.
• Comparative metabolism and kinetics of coumarin in mice and rats / S. L. Born, A. M. Api, R. A. Ford, [et al.] // Food Chem. Toxicol. –2003. –№41. –P. 247–258.
• BeckleyWKartey S. A. J. Comparative in vitro skin absorption and metabolism of coumarin (1,2WbenzopyW rone) in human, rat and mouse / S. A. J. BeckleyWKartey, S. A. M. Hotchkins, M. Capel // Toxicology and Applied Pharmacology . –1997. –№ 145. –P. 34–42.
• Metabolism and toxicity of coumarin on cultured human, rat, mouse and rabbit hepatocytes / D.Ratanasavanh, D. Lamiable, M. Biour [et al.] // Fundam. Clin. Pharmacol. –1996. –V.10(6). – P. 504–510.
• Born S. L. OWhydroxyphenylacetaldehyde (oWHPA) is a hepatotoxic metabolite of coumarin / S. L. Born, J. K. Hu, L. D. LehmanWMcKeeman // Toxicological Sciences. –1998. –V. 42. –№ 1–S. –P. 400–403.
• MechanismWbased inactivation of human liver cytochrome P450 2A6 by 8Wmethoxypsoralen / L. L. Koenigs, R. M. Peter, S. J. Thompson [et al.] // Drug Metabolism and Disposition . –1997. –№ 25. – P. 1407–1415.
• Fentem J. H. Species differences in the metabolism and hepatotoxicity of coumarin / J. H. Fentem, J. R. Fry // Comp. Biochem. Physiol. –1993. –№ 104. –P. 1–8.
• Fentem J. H. Species differences in the hepatotoxicity of coumarin: A comparison of rat and Mongolian gerbil / J. H.Fentem, J. R. Fry, N. W. Thomas // Toxicology. –1992. –№ 71. –P. 129–136.
• iquid chromatographic determination оf the glutathione conjugate and ring opened metabolites formed from coumarin epoxidation. / Vassallo, J. D., Morall, S. W., Fliter, [et al.] // J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. –2003. –№ 794. –P. 257–271.
• Gangolli S. D. Studies on the metabolism and hepatotoxicity of coumarin in the baboon / S. D.Gangolli, W. H . Shilling, P.Grasso , L. F. Gaunt //Biochem. Soc Trans. –1974. –№ 2. –P. 310–312.
• 22. Evans J. G. TwoWyear toxicity study on coumarin in the baboon / J. G. Evans, I. F. Gaunt, B. G. Lake // Food Cosmet. Toxicol. –1979. –№ 17. –P. 187–193.
• 23. Ueno I. NonWcarcinogenic response to coumarin in Syrian golden hamsters / I.Ueno, I. Hirono // Food Cosmet. Toxicol. –1980. –№ 19. –P. 353–355.
• 24. Wood A. W. Genetic variation in coumarin hydroxylase activity in the mouse (mus musculus) / A. W. Wood, A. H. Conney // Science. –1974. –№ 185 (4151). –P. 612–614.
• 25. Endell W. Coumarin toxicity in different strains of mice. / W. Endell, Seidel G. // Agents Actions. –1978. –№8. –P. 299–302.
• 26. Metabolism of coumarin and 7Wethoxycoumarin by rat, mouse, guinea pig, Cynomolgus monkey and human precisionWcut liver slices / A. Steensma, J. A. Beamand, D. G. Walters [et al.] // Xenobiotica . –1994. –№ 24. –P. 893W907.
• 27. Pelkonen O. CYP2A6: a human coumarin 7Whydroxylase / Pelkonen O., Rautio A., Raunio H., Pasanen M. // Toxicology . –2000. –V. 144. –Issues 1–3. –P. 139–147.
• 28. A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7W hydroxylation to 3Whydroxylation of coumarin / H.Hadidi, K.Zahlsen, J. R. Idle [et al.] // Food and Chemical Toxicology . –1997. –№ 35. –P. 903–907.
• 29. Studies on the mechanism of coumarinWindiced toxicity in rat hepatocytes: Comparison with dihydroW coumarin and other coumarin metabolites / B. G. Lake, T. J. Gray, J. G.Evans [et al.] // Toxicol. Appl. Pharmacol. –1989. –№ 97. –P. 311–323.
• 30. Studies on the induction of cholangiofibrosis by coumarine on the rat / J. G. Evans, E. C. Appleby, B. G. Lake [et al.] // Toxicology. –1989. –№ 55. – P. 207–224.
• 31. Effect of inducers of cytochrome P450 on the metabolism of [3WHC] coumarin by rat hepatic microsomes / M. M. Peters, D. G.Walters, B. van Ommen [et al.] // Xenobiotica. –1991. –№ 21. –P. 499–514.
• 32. Identification of the human liver cytochrome PW450 responsible for coumarin 7Whydroxylase activity/ J. S. Miles, A. W. McLaren , L. M. Forrester [et al.] // Biochem. J. –1990. –№ 267. –P. 365–371.
• 33. Williams R. T. The influence of enterohepatic circulation on toxicity of drugs/ R. T. Williams, P. Millburn, R. L. Smith //Ann. N. Y. Acad. Sci. –1965. –123. –P. 110–113.
• 34. Shilling W. H. Metabolism of coumarin in man / W. H. Shilling, R. F. Crampton, R. C. Longland // Nature. –1969. –№ 221. –P. 664–665.
• 35. Feuer G. Liver response tests. VII Coumarin metabolism in relation to the inhibition of ratWliver glucose 6W phosphatase / G. Feuer, Golberg L., Gibson K. //Food. Cosmet. Toxicol. –1966. –№ 4. –P. 157–167.
• 36. Berenbaum M. Coumarins and caterpillars: a case for coevolution. / M.Berenbaum // Evolution. –1983. –№ 37(1). –P. 163–179.
• 37. Guilbault G.G Practical fluorescence / edited by George G. Guilbault . –New York. USA. –1990. –249 p.
• 38. Marshall M. E. Growth–inhibitory effects of coumarin (1,2Wbenzopyrone) and 7Whydroxycoumarin on human malignant cell lines in vitro /M. E. Marshall , K. Kervin, C. Benefield // J. Cancer Res. Clin. Oncol . –1994, V. 120. –suppl.1. –P. 3–10.
• 39. Seliger B. 7WHydroxycoumarin inhibits oncogeneWinduced transformation of murine fibroblasts / B. Seliger, H. Pettersson // J. Cancer Res. Clin. Oncol . –1994. –№ 20 (Suppl). –P. 23–27.
• 40. Antitumor and immunomodulatory affect of coumarin and 7Whydroxycoumarin against Sarcoma 180 in mice / T.N. Stefanova, N.J. Nikolova, R.A. Toshkova [et al.] // Journal of experimental therapeutics & oncology. –2007. –№ 6(2). –P. 107–115.
• 41. Hoult J. Pharmacological and biochemical actions of simple coumarins:natural products with therapeutic potential / J. Hoult, M. Paya // Gen. Pharmacol. –1996. –№ 7. –P. 713–722.
• 42. Kostova I. Synthetic and natural coumarins as cytotoxic agents / I. Kostova // Curr. Med. Chem. –AntiW Cancer Agents. –2005. –V. 5. –№. 1. –P. 29–46
• 43. Umbelliferone analogs and their potential to inhibit benzo(a)pyreneW and hydrogen peroxideWinduced mutations / S.P. Pillai, S.R.Menon, L.A.Mitscher [et al.] // J. Nat. Prod. –1999. –V. 62. –P. 1358–1362.
• 44. Evaluation of antigenotoxicity effects of umbelliprenin on human peripheral lymphocytes exposed to oxidative stress / F. Soltani, F. Mosaffa, M. Iranshahi [et al.] //Cell. Biol. Toxicol. –2009. –№ 25(3). –P. 291–296.
• 45. Wojkowich K. Ultrasound investigation of the effect of 4Whydroxycoumarin and umbelliferon on lipid bilayW ers / K.Wojkowich // Molecular and Quantum Acoustics . –2007. –V. 28. –P. 285–292.
• 46. Effects of umbelliferone in a murine model of allergic airway inflammation / J. F. Vasconcelos, M. M. Teixeira, J. M. BarbosaWFilho [et al.] // European Journal of Pharmacology. –2009. –V. 609. –Issues 1–3. – P. 126–131
• 47. Effect of umbelliferone (7Whydroxycoumarin, 7WHOC) on the enzymatic, edematogenic and necrotic activW ities of secretory phospholipase A2 (sPLA2) isolated from Crotalus durissus collilineatus venom / D.O. Toyamaa, S. Marangonib, E.B.S. DizWFilhob [et al.] // Toxicon. –2009. –V. 53. –Issue 4. –P. 417–426. 44 Проблеми харчування 34/2009
• 48. Hardt T.J. Investigation of the dose response relationship upon intraperitoneal administration of coumarin and 7Whydroxycoumarin on the carrageenan induced edema of the rats hind paw / T.J. Hardt , W.A. Ritschell // Arzneim. Forsch. –1983. –V. 33. –issue 12. –P. 1662–1666.
• 49. Янченко П.С. Виділення та вивчення деяких кумаринів і хромонів із рослин родин бобові та селеW рові та їх ліпазотропна активність / П.С. Янченко, А.М. Ковальова, Г.В. Георгієвський, А.М. КомісаW ренко // ФАРМАКОМ. –2004. –№ 2. –C. 1–7.
• 50. Ramesh B. Protective effect of umbelliferone on membranous fatty acid composition in streptozotocinW induced diabetic rats / B.Ramesh, P. Viswanathan P., K.V.Pugalendi // European Journal of Pharmacology. –2007. –V. 566. –Issues 1–3. –P. 231–239.
• 51. Ramesh B. Impact of umbelliferone (7–hydroxycoumarin) on hepatic marker enzymes in streptozotocin diabetic rats /B. Ramesh , K.V. Pugalendi // Indian J. Pharmacol. –2006. –№ 38. –P. 209–210.
• 52. Ramesh B. Antihyperglycemic effect of umbelliferone in STZWdiabetic rats. / B. Ramesh, K.V. Pugalendi // J. Med. Food . –2006. –№ 9 (4). –P. 562–566.
• 53. Ramesh B. Influence of umbelliferone on membrane–bound ATPases in streptozotocinWinduced diabetic rats / B. Ramesh , K.V. Pugalendi // Pharmacol. Rep. –2004. –№ 59 (3). –P. 339–348.
• 54. Ramesh B. Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats / B. Ramesh , K.V. Pugalendi // Yale J. Biol. Med. –2005. –№ 78(4). –P. 189–196.
• 55. Ramesh B. Impact of umbelliferone on erythrocyte redox status in STZWdiabetic rats / B. Ramesh, K.V. Pugalendi // Yale Journal of Biology and Medicine. –2005. –№ 78. –P. 11–18.
• 56. Ramesh B. Effect of umbelliferone on tail tendon collagen and haemostatic function in streptozotocinW diabetic rats / B. Ramesh , K.V. Pugalendi // Basic Clin. Pharmacol. Toxicol. –2007. –V. 101. –№ 2. – P. 73–77.