ABC> Vol.4 No.4, June 2014

Bio-Medical Aspects of Purine Alkaloids

DownloadDownload as PDF (Size:647KB)  HTML   XML  PP. 274-280  

ABSTRACT

This review shortly summarized bio-medical activities of purine alkaloids, caffeine (caf), theophyline (top) and theobromine (tob). Caffeine potentiates the cytotoxicity of a variety of DNA domaging agents. Caffeine increased antitumor activity of some cancerostatic drugs. Caffeine inhibits the carcinogenic activity of cigarette smoke, significantly potentiating the therapeutic effect of acetaminophenol, cyclophosphoramide, enhances lipid oxidation, affects the central nervous system and alters cardiovascular system. Theophyline has expressive anti-inflammatory and antiasthmatic effect, and enhanced mobilization of lipid reduces the brain regional adenylate cyclase activity, facilitates glucose inhibition. Theophyline is muscle relaxant, vasodilator, diuretic and cardiac stimulant. Theobromine increases antitumor activity of adriamycin and doxorubicin, has expressive anti-inflammatory effect and it is classical diureticum. Several examples of caffeine with some organic substrates as well as with copper are also outlined. Increasing activity of the respective drugs in the present of the purine alkaloids can be ascribed to direct interaction as was proved by X-ray data of some caffeine adducts with organic substances as well as Cu(II) complexes.

Cite this paper

Melnik, M. , Sprusansky, O. and Musil, P. (2014) Bio-Medical Aspects of Purine Alkaloids. Advances in Biological Chemistry, 4, 274-280. doi: 10.4236/abc.2014.44033.

References

[1] Tomita, K. and Tsuchija, H. (1989) Caffeine Enhancement of the Effect of Anticancer Agents on Human Sarcoma Cells. Cancer Science, 80, 83-88.
http://dx.doi.org/10.1111/j.1349-7006.1989.tb02249.x
[2] Traganos, F., Kapucinski, J., Gong, J., Ardelt, B. and Darzynkiewicz, R.J. (1993) Caffeine Prevents Apoptosis and Cell Cycle Effects Induced by Camptothecin or Topotecan in HL-60 Cells. Cancer Research, 53, 4613-4618.
[3] Shoyab, M. (1979) Caffeine Inhibits the Binding of Dimethylbenz(a)anthracene to Murine Epidermal Cells DNA in Culture. Archives of Biochemistry and Biophysics, 196, 307-310.
http://dx.doi.org/10.1016/0003-9861(79)90582-4
[4] Traganos, F., Kamiska-Eddy, B. and Darzynkiewicz, Z. (1991) Caffeine Reverses the Cytotoxic and Cell Kinetic Effects of Novantrone(mitoxantrone). Cell Proliferation, 24, 305-319.
http://dx.doi.org/10.1111/j.1365-2184.1991.tb01159.x
[5] Traganos, F., Kapucinski, J., Darzynkiewicz, Z. (1991) Caffeine Modulates the Effects of DNA-intercalating Drugs in Vitro: A Flow Cytometric and Spectrophotometric Analysis of Caffeine Interaction with Novantrone, Doxorubicin, Ellipticine, and the Doxorubicin Analogue AD198. Cancer Research, 51, 3682-3689.
[6] Sadzuka, Y., Machizuki, E. and Tatino, Y. (1993) Caffeine Modulates the Antitumor Activity and Toxic Side Effects of Adriamycin. Cancer Science, 84, 348-353.
http://dx.doi.org/10.1111/j.1349-7006.1993.tb02877.x
[7] Sadzuka, Y., Machizuki, E. and Tatino, Y. (1995) Mechanism of Caffeine Modulation of the Antitumor Activity of Adriamycin. Toxicology Letters, 75, 39-49.
http://dx.doi.org/10.1016/0378-4274(94)03154-Y
[8] Sadzuka, Y., Iwazaki, A., Miyagshima, Y., Nozawa, Y. and Hirota, S.J. (1995) Caffeine-Biochemical Modulator of Axdriamycin. Cancer Science, 86, 594-599.
http://dx.doi.org/10.1111/j.1349-7006.1995.tb02439.x
[9] Tomita, K., Tsuchiya, H. and Sasaki, T. (1989) The Combination Cis-Platin, Adriamycin and Caffein and Wide Effect Antitumor activity. Gan to Kagater Rycho, 16, 576-584.
[10] Furusawa, S., Malkawa, L., Fujimura, T., Takayanage, Y. and Sasaki, K. (1993) Influence of Caffeine on Effect of Pirarubicin. Research Communications in Substance Abuse, 14, 179-192.
[11] Roberts, J.J. (1981) Damage in DNA by Cis-Platin. Advances in Inorganic Biochemistry, 3, 273-276.
[12] Shinomiya, N., Shinimiya, M., Wakaiyama, H., Katsura, Y. and Rokutanda, M. (1994) Enhancement of CDDP Cytotoxicity by Caffeine Is Characterized by Apoptotic Cell Death. Experimental Cell Research, 210, 236-242.
http://dx.doi.org/10.1006/excr.1994.1035
[13] Tomita, A. and Tsuchiya, H. (1989) Cytotoxicity of Cis-Platin in the Presence of Caffeine. Clinical Therapeutics, 11, 43-52.
[14] Sadzuka, Y., Egawa, Y., Savanish, H., Miyamoto, K. and Sonobe, T. (2002) Effects of Xanthine Derivatives on the Influx and Efflux of Doxorubicin in P388 and DOX-Resistant P388 Leukemia Cells. Toxicology Letters, 135, 137-144.
http://dx.doi.org/10.1016/S0378-4274(02)00227-8
[15] Van der Berg, H.W., Favol, H.N.A. and Roberts, J.J. (1977) Caffeine as Inhibition of DNA Repain. Journal of Hematology & Oncology, 7, 349-373.
[16] Rothwell, A. (1974) Dose-Related Inhibition of Chemical Carcinogenesis in Mouse Skin by Caffeine. Nature, 252, 69-70.
http://dx.doi.org/10.1038/252069a0
[17] Beaulac-Baillargeon, L. and Desrosiers, C. (1987) Caffeine-Cigarette Interaction on Fetal Growth. American Journal of Obstetrics & Gynecology, 157, 1236-1240.
http://dx.doi.org/10.1016/S0002-9378(87)80301-0
[18] Gaudin, D. and Yielding, K.L. (1969) Response of a “Resistant” Plasmacytoma to Alkylating Agents and X-Ray in Combination with the Excision Repair Inhibitors Caffeine and Chloroquine. Proceedings of the Society for Experimental Biology and Medicine, 131, 1413-1416.
http://dx.doi.org/10.3181/00379727-131-34119
[19] Rainska-Giezek, T. (1995) Paracetamol. Roczniki Pomorskiej Akademii Medycznej Im. Gen. Karola Swierczewskiego W Szczecinie, 41, 69-84.
[20] El-Bassiony, S.F., Abo-Hashim, N., Sirag, S.M. and El-Ghazaly, Y. (1995) Influence of Caffeine on Paracetamol Induced Hepatotoxicity in Rats. Journal of Environmental Sciences (Mansoura, Egypt), 10, 233-242.
[21] Iqbal, N., Ahmad, B., Janbaz, K.H., Ul Hassan Giland, A. and Sarfeuaz, K. (1995) The Effect of Caffeine on the Pharmacokinetics of Acetaminophen in Man. Biopharmaceutics & Drug Disposition, 16, 481-487.
http://dx.doi.org/10.1002/bdd.2510160606
[22] Anderson, E.D. and Hickey, S. (1994) Effects of Caffeine on the Metabolic and Catecholamine Responses to Exercise in 5 and 28 Degrees. Medicine and Science in Sport and Exercise, 26, 453-458.
http://dx.doi.org/10.1249/00005768-199404000-00009
[23] Nishiyama, Y., Ikeda, T., Takamutsu, M., Kiso, Y., Shibata, H., Fusheki, T. and Moritane, T. (2002) Influence of Caffeine Ingestion on Autonomic Nervous Activity during Endurance Exercise in Humans. European Journal of Applied Physiology, 87, 475-480.
http://dx.doi.org/10.1007/s00421-002-0678-1
[24] Leberman, H.R., Fine, B.J., Kobrick, J.L. and John, J.D.E. (1993) Study of Effects Caffeine on Central Nervous System. AGARD Conference Proceedings, 533.
[25] Wurts, S.W. and Edgar, D.M. (2000) Caffeine during Sleep Deprivation: Sleep Tendency and Dynamics of Recovery Sleep in Rats. Pharmacology, Biochemistry and Behavior, 65, 155-162.
http://dx.doi.org/10.1016/S0091-3057(99)00173-2
[26] Engels, H.J., Wirth, J.C., Celek, S. and Dorsey, J.L. (1999) Influence of Caffeine on Metabolic and Cardiovascular Functions during Sustained Light Intensity Cycling and at Rest. International Journal of Sport Nutrition, 9, 361-370.
[27] Lim, D.Y., Lee, J.M., Kim, W.S., Kim, S.B., Lee, E.H., Lee, J.B. and Ko, S.T. (1991) Studies on Secretion of Catecholamine Evoked by Caffeine from the Isolated Perfused Rat Adrenal Gland. Archives of Pharmacal Research, 14, 55-67.
http://dx.doi.org/10.1007/BF02857816
[28] Su, J.Y. (1991) Influence of Caffeine, Ca2+, and Mg2+ on Ryanodine Depression of the Tension Transient in Skinned Myocardial Fibers of the Rabbit. Pflügers Archiv: European Journal of Physiology, 421, 1-6.
[29] Kagawa, Y., Mayumi, N., Higashigawa, S., Katsuda, K., Kakito, M., Inagaki, S., Ohsugi, H., Sumida, K., Sakurai, M. and Edobashi, T. (1992) Caffeine Facilitates the Conversion of Allopurinol to Oxipurinol. Mie Medical Journal, 42, 203-207.
[30] Valdes, M., Shaye, R., Joseph Jr., F. and Nakamoto, T. (1992) The Effects of Caffeine on the Maxillary Composition in the Newborn Rat. Calcified Tissue International, 50, 165-168.
http://dx.doi.org/10.1007/BF00298795
[31] Kruk, B., Chmura, J., Krzeminski, K., Ziemba, A.W., Nazar, K., Pekkarinen, H. and Kaciuba-Uscilko, H. (2001) Influence of Caffeine, Cold and Exercise on Multiple Choice Reaction Time. Psychopharmacology, 157, 197-201.
http://dx.doi.org/10.1007/s002130100787
[32] Ito, K., Lim, S., Caramori, G., Cosiio, B., Chung, K.F., Adcock, T.M. and Barnes, P.J. (2002) A Molecular Mechanism of Action of Theophylline: Induction of Histone Deacetylase Activity to Decrease Inflammatory Gene Expression. Proceedings of the National Academy of Sciences of the United States of America, 99, 8921-8926.
[33] Sagara, H., Makino, S., Chibana, N., Ota, M., Holgate, S.T., Church, M.K. and Fukuda, T. (2001) Theophyline at Therapeutic Concentrations Inhibits NF-κB Activation in Human Lung Mast Cells. International Archives of Allergy and Immunology, 124, 371-375.
http://dx.doi.org/10.1159/000053761
[34] Louis, R., Bettiol, J., Cataldo, D., Sele, J., Henquet, M. and Rademecker, M. (2000) Effect of a 4-Week Treatment with Theophylline on Sputum Eosinophilia and Sputum Eosinophil Chemotactic Activity in Steroid-Naive Asthmatics. Clinical & Experimental Allergy, 30, 1151-1160.
http://dx.doi.org/10.1046/j.1365-2222.2000.00867.x
[35] Takeuchi, M., Hayakawa, A., Takagi, K., Hiramatsu, K., Shimizu, Y., Matsumoto, S., Hiramatsu, T., Ito, Y., Kume, H., Suzuki, R. and Yamaki, K. (1999) Theophylline Induces Apoptosis of the IL-3 Activated Eosinophils of Patients with Bronchial Asthma. Apoptosis, 4, 461-468.
http://dx.doi.org/10.1023/A:1009656527168
[36] Lin, Z.T., Huang, H.L., Zhao, L.N., Yu, Q.S. and Zhong, N.S. (1998) Inhibited of Theophylline on Factor (PAF) in Asthma. Zhongguo YaoYau-Lixue Tongbao, 14, 30-32.
[37] Blake, K. (1999) Theophylline. In: Murphy, S. and Kelly, H.W., Eds., Pediatric Asthma, MarcelDekker, New York, 363-431.
[38] Ichiyama, T., Hasegawa, S., Matsubara, T., Hayashi, T. and Furukawa, S. (2001) Theophylline Inhibits NF-Kappa B Activation and I Kappa B Alpha Degradation in Human Pulmonary Epithelial Cells. Naunum-Schmiedeberg’s Archieves of Pharmacology, 364, 558-561.
[39] Alhomida, A.S. (2001) Oral Theophylline Changes Renal Carnitine Palmitoyltransferase Activity in Rats. Archives of Medical Research, 32, 394-399.
http://dx.doi.org/10.1016/S0188-4409(01)00299-5
[40] Alhomida, A.S. (2001) Evaluation of Theophylline-Stimulated Changes in Carnitine Palmitoyltransferase Activity in Skeletal Muscle and Liver of Rats. Journal of Enzyme Inhibition and Medicinal Chemistry, 16, 177-183.
http://dx.doi.org/10.1080/14756360109162367
[41] Alhomida, A.S. (1998) Evaluation of the Impact of Theophylline Treatment on Carnitine Acetyltransferase Activity in RAT Kidney. In Vivo, 12, 553-558.
[42] Alhomida, A.S. (1999) Study of Theophylline on the Level of Carnitine in the Cardiac Tissues of Rats. Journal of Biochemistry Molecular Biology and Biophysics, 2, 273-280.
[43] Mandal, M. and Podar, M.K. (2001) Brain Regional Adenylate Cyclase Activity: Effect of Theophylline under Non-tolerant and Tolerant Conditions. Biogenic Amines, 16, 251-268.
[44] Okumura, M., Kai, H., Shinozawa, S., Isohama, Y., Takahama, K. and Miyata, T. (1997) Effects of Xanthine Derivatives on Phosphatidylcholine Secretion in Rat Type II Pneumocytes in the Presence of Activated Eosinophils. Japanese Journal of Pharmacology, 75, 425-432.
[45] Faang, N. and Nuttall, F.Q. (1997) The Effect of Caffeine and Caffeine Analogs on Rat Liver Phosphorylase a Activity. Journal of Pharmacology and Experimental Therapeutics, 280, 1312-1318.
[46] Bandyopadhyay, B.C. and Poddar, M.K. (1997) Theophylline-Induced Changes in Mammalian Adenosine Deaminase Activity and Corticosterone Status: Possible Relation to Immune Response. Methods and Findings in Experimental and Clinical Pharmacology, 19, 181-184.
[47] Oner, P., Gurdol, F., Oner-Iyidon, Y., Kolanci, C. and Buyukozturk, S. (1999) Evaluation of the Effect of Low-Dose Oral Theophylline Therapy on Some Bone Turnover Markers and Serum Prolidase I Activity in Mild Asthmatics. Pharmacological Research, 40, 189-193.
http://dx.doi.org/10.1006/phrs.1999.0486
[48] Kawakami, E., Arai, T. and Nakamura, U. (1999) Effects of Medium Containing Heparin and Theophylline on Capacitation and Metabolic Enzyme Activities of Ejaculated spermatozoa from Dogs with Asthenozoospermia. Animal Reproduction Science, 54, 251-259.
http://dx.doi.org/10.1016/S0378-4320(98)00158-4
[49] Sako, J., Hori, S. and Kawamura, M. (1998) Effect of Theophylline, Caffeine and Dimethylxanthines on Endogenous Glucocorticoid Levels in Mice. A Possible Mechanism of Anti-Inflammatory Activity of Theophylline. Pharmacy and Pharmacology Communications, 4, 499-501.
[50] Ebisuzaki, Y., Boyle, P.D. and Smith, J.A. (1997) Methylxanthines. I. Anhydrous Theophylline. Acta Crystallographica Section C, Crystal Structure Communications, 53, 777-779.
http://dx.doi.org/10.1107/S0108270197001960
[51] Nakao, S., Fuji, S., Sakaki, T. and Tomita, K. (1977) Crystal and Molecular-Structure of 2-1 Molecular-Complex of Theophylline with Phenobarbital. Acta Crystallographica Section C, Crystal Structure Communications, 33, 1373-1376.
[52] Del Bartolo Ruenis, A.P., Rosalen, P.L., Volpato, C.M. and Gropo, F.C. (2000) Effects of Caffeine and Theophylline on the Development of Dental Caries in Rats. Biological & Pharmaceutical Bulletin, 23, 339-343.
http://dx.doi.org/10.1248/bpb.23.339
[53] Sadzuka, Y., Iwazaki, A. and Hirota, S. (1998) Effects of Methylxanthine Derivatives on Antitumor Activity and Toxic Side Effect of Adriamycin Induced by Inhibition of DNA Biosynthesis. Yakugaku Zasshi, 118, 179-187.
[54] Kakuyama, A. and Sadzuka, Y. (2001) Effect of Methylxanthine Derivatives on Doxorubicin Transport and Antitumor Activity. Current Drug Metabolism, 2, 379-395.
http://dx.doi.org/10.2174/1389200013338270
[55] Nomura, T. (1983) Comparative Inhibiting Effects of Methylxanthines on Urethan-Induced Tumors, Malformations, and Presumed Somatic Mutations in Mice. Cancer Research, 43, 1342-1346.
[56] Hosseinzadeh, H. and Deghan, R. (1999) Anti-Inflammatorynactivity of Purine Alkaloids. Pharmaceutical and Pharmacological Letters, 9, 18-19.
[57] Pollard, I., Locquet, O., Odette, S., Solvar, A. and Magre, S. (2001) Effects of Caffeine and Its Reactive Metabolites Theophylline and Theobromine on the Differentiating Testis. Reproduction, Fertility and Development, 13, 435-441.
http://dx.doi.org/10.1071/RD01018
[58] Rettie, E.A. and Dieter, H.D. (2000) Can Caffeine Metabolism Be Used as an In-Vivo Probe for Human Flavin-Containing Monooxygenase Activity? Pharmacogenetics, 10, 275-277.
http://dx.doi.org/10.1097/00008571-200004000-00010
[59] Kuribara, H., Asahi, T. and Tadokoro, S. (1992) Behavioral Evaluation of Psycho-Pharmacological and Psychotoxic Actions of Methylxanthines by Ambulatory Activity and Discrete Avoidance in Mice. Journal of Toxicological Sciences, 17, 81-90.
http://dx.doi.org/10.2131/jts.17.81
[60] Shefter, E. (1968) Structural Studies on Complexes II. Crystal and Molecular Structure of a 1:1 Caffeine and 5-Chlorosalicyclic Acid Complex. Journal of Pharmaceutical Sciences, 57, 1163-1168.
http://dx.doi.org/10.1002/jps.2600570715
[61] Craven, B.M. and Gartland, G.L. (1974) The 2:1 Crystal Complex of 5,5-diethylbarbituric Acid (Barbital) and Caffeine. Acta Crystallographica Section B, 30, 1191-1195.
http://dx.doi.org/10.1107/S0567740874004559
[62] Mercer, A. and Trotter, J. (1978) Crystal and Molecular Structure of 1,3,7-trimethyl-2,6-Purinedione Hydrochloride Dihydrate (Caffeine Hydrochloride Dihydrate). Acta Crystallographica Section B, 34, 450-453.
http://dx.doi.org/10.1107/S0567740878003337
[63] Cingi, M.B., Villa, A.C., Manfredotti, A.G. and Guastini, C. (1972) Crystal Structure of Caffeine-Hydrochloride Dihydrate. Crystal Structure Communications, 1, 363-365.
[64] Bondoli, G., Biagini, M.C., Clemente, D.A. and Rizzardi, G. (1976) Preparation, Crystal and Molecular Structure of aquadichlorocaffeinecopper(II). Inorganica Chimica Acta, 20, 71-78.
http://dx.doi.org/10.1016/S0020-1693(00)94093-3
[65] Koman, M., Melnik, M., Moncol, J. and Glowiak, T. (2000) Caffeine in Copper(II) Complexes: Crystal and Molecular Structure of di(caffeine)tetrakis(naproxenato) dicopper(II). Inorganic Chemistry Communications, 3, 489-492.
http://dx.doi.org/10.1016/S1387-7003(00)00122-2
[66] Valach, F., Melnik, M., Bernardinelli, G. and From, K.M. (2006) A Structural Study of Copper(II) Carboxylates: Crystal Structure and Physical Characterisation of [Cu2(2-bromopropanoato)4(caffeine)2]. Journal of Chemical Crystallography, 36, 571-580.
http://dx.doi.org/10.1007/s10870-006-9102-8
[67] Segla, P., Miklos, D. and Melnik, M. (2010) Structures, Physico-Chemical Properties and Biological Activities of Copper(II) Pyridinecarboxylates. Nova Science Publishers, Inc., New York, 1-82.
[68] Dudová, B., Hudecová, D., Pokorny, R., Mikulásová, M., Palicová, M., Segl'a, P. and Melník, M. (2001) Copper Complexes with Bioactive Ligands. Part I-Antimicrobial Activity, Folia Microbiologica, 46, 379-384.
http://dx.doi.org/10.1007/BF02814425
[69] Dudova, B., Hudecova, D., Pokorny, R., Mickova, M., Palicova, M., Segla, P. and Melnik, M. (2002) Copper Complexes with Bioactive Ligands—Part II—Antifungal Activity. Folia Microbiologica, 47, 225-229.
http://dx.doi.org/10.1007/BF02817642

  
comments powered by Disqus

Copyright © 2014 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.