A Novel One-Pot and Efficient Procedure for Synthesis of New Fused Uracil Derivatives for DNA Binding
Author(s)
Bothaina A. Mousa1,
Ashraf H. Bayoumi2*,
Makarem M. Korraa1,
Mohamed G. Assy3,
Samar A. El-Kalyoubi4
Affiliation(s)
1 Department of Organic Chemistry, Faculty of Pharmacy, Cairo University, Giza, Egypt. 2 Department of Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt. 3 Department of Organic Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt. 4 Department of Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
1 Department of Organic Chemistry, Faculty of Pharmacy, Cairo University, Giza, Egypt. 2 Department of Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt. 3 Department of Organic Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt. 4 Department of Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
ABSTRACT
Hydrazinolysis of 6-chloro-1-methyluracil followed by condensation of the product with different aromatic aldehyde gives the respective hydrazones which undergoes oxidative cyclization using thionyl chloride to obtain pyrazolo[3,4-d]pyrimidines in good yields. On the other hand, nitrosation of 6-aminouracils followed by the reaction with different arylidineanilines gives new xanthine derivatives. Finally, indenopyrrolopyrimidine and indenopteridine are obtained in good yields via the reaction of 6-aminouracils and 5,6-diaminouracil with ninhydrin respectively. The newly synthesized compounds show binding, chelation and fragmentation of the nucleic acid DNA.
Hydrazinolysis of 6-chloro-1-methyluracil followed by condensation of the product with different aromatic aldehyde gives the respective hydrazones which undergoes oxidative cyclization using thionyl chloride to obtain pyrazolo[3,4-d]pyrimidines in good yields. On the other hand, nitrosation of 6-aminouracils followed by the reaction with different arylidineanilines gives new xanthine derivatives. Finally, indenopyrrolopyrimidine and indenopteridine are obtained in good yields via the reaction of 6-aminouracils and 5,6-diaminouracil with ninhydrin respectively. The newly synthesized compounds show binding, chelation and fragmentation of the nucleic acid DNA.
KEYWORDS
6-Chloro-1-methyluracil, Pyrazolo[3, 4-d]pyrimidines, 6-Aminouracils, Xanthine, Indenopyrrolopyrimidine and Indenopteridine
6-Chloro-1-methyluracil, Pyrazolo[3, 4-d]pyrimidines, 6-Aminouracils, Xanthine, Indenopyrrolopyrimidine and Indenopteridine
Cite this paper
Mousa, B. , Bayoumi, A. , Korraa, M. , Assy, M. and El-Kalyoubi, S. (2015) A Novel One-Pot and Efficient Procedure for Synthesis of New Fused Uracil Derivatives for DNA Binding. International Journal of Organic Chemistry, 5, 37-47. doi: 10.4236/ijoc.2015.51005.
Mousa, B. , Bayoumi, A. , Korraa, M. , Assy, M. and El-Kalyoubi, S. (2015) A Novel One-Pot and Efficient Procedure for Synthesis of New Fused Uracil Derivatives for DNA Binding. International Journal of Organic Chemistry, 5, 37-47. doi: 10.4236/ijoc.2015.51005.
References
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http://dx.doi.org/10.1016/S0968-0896(01)00294-2 [20] Nasr, M.N. and Gineinah, M.M. (2002) Pyrido[2, 3-d]pyrimidines and Pyrimido[5’,4’:5, 6]pyrido[2, 3-d]pyrimidines as New Antiviral Agents: Synthesis and Biological Activity. Archiv der Pharmazie, 335, 289-295.
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http://dx.doi.org/10.1016/j.ejmech.2013.08.024 [22] Sondhi, S.M., Johar, M., Rajvanshi, S., Dastidar, S.G., Shukla, R., Raghubir, R., et al. (2001) Anticancer, Antiinflammatory and Analgesic Activity Evaluation of Heterocyclic Compounds Synthesized by the Reaction of 4-Isothiocyanato- 4-methylpentan-2-one with Substituted o-Phenylenediamines, o-Diaminopyridine and (Un)Substituted o. Australian Journal of Chemistry, 54, 69-74.
http://dx.doi.org/10.1071/CH00141 [23] Youssif, S. and Assy, M. (1996) Fervenulin, 4-Deazafervenulin and 5-Deazaalloxazines Analogue: Synthesis and Antimicrobial Activity. Journal of Chemical Research, 442, 2546. [24] Herrmann, M., Lorenz, H.M., Voll, R., Grünke, M., Woith, W. and Kalden, J.R. (1994) A Rapid and Simple Method for the Isolation of Apoptotic DNA Fragments. Nucleic Acids Research, 22, 5506-5507.
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http://dx.doi.org/10.1002/jhet.5570350428 [28] Youssif, S. (1997) DMF Acetals as Alkylating and Cyclizing Agents: A Facile Route to Substituted Pyrazolo[3,4-d] pyrimidine-4,6(5H,7H)-diones. Chemical Monthly, 128, 493-501.
http://dx.doi.org/10.1007/BF00806857 [29] Hutzenlaub, W. and Pfleiderer, W. (1979) Purines, XIII. Simplified Syntheses of 7-Methy- and 1,7-Dimethylxanthines and Uric Acids. Liebigs Annalen der Chemie, 1847-1854. [30] Youssif, S. (2004) 6-Aminouracil as Precursors for the Synthesis of Fused Di- and Tricyclic Pyrimidines. Journal of Chemical Research, 341-343. [31] Youssif, S. and Ageli, F. (2008) One-Pot Synthesis of Fused 2-Thiouracils: Pyrimidopyrimidines, Pyridopyrimidines and Imidazolopyrimidines. Zeitschrift für Naturforschung, 63b, 860-864. [32] Peet, N.P., Huber, E.W. and Huffman, J.C. (1995) Reaction of Ninhydrin with β-Dicarbonyl Compounds. Journal of Heterocyclic Chemistry, 32, 33-41.
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http://dx.doi.org/10.1002/cber.19550880825
[1] Brown, D.J. (1984) Pyrimidines and Their Benzo Derivatives. Comprehensive Heterocyclic Chemistry, 3, 57-155.
http://dx.doi.org/10.1016/B978-008096519-2.00035-7 [2] Wamhoff, H., Dzenis, J. and Hirota, K. (1992) Uracils: Versatile Starting Materials in Heterocyclic Synthesis. Advances in Heterocyclic Chemistry, 55, 129-259.
http://dx.doi.org/10.1016/S0065-2725(08)60222-6 [3] González-Vallinas, M., Molina, S., Vicente, G., de la Cueva, A., Vargas, T., Santoyo, S., García-Risco, M.R., Fornari, T., Reglero, G. and de Molina, A.R. (2013) Antitumor Effect of 5-Fluorouracil Is Enhanced by Rosemary Extract in Both Drug Sensitive and Resistant Colon Cancer Cells. Pharmacological Research, 72, 61-68.
http://dx.doi.org/10.1016/j.phrs.2013.03.010 [4] Innominato, P.F., Lévi, F.A. and Bjarnason, G.A. (2010) Chronotherapy and the Molecular Clock: Clinical Implications in Oncology. Advanced Drug Delivery Reviews, 62, 979-1001.
http://dx.doi.org/10.1016/j.addr.2010.06.002 [5] Isanbor, C. and O’Hagan, D. (2006) Fluorine in Medicinal Chemistry: A Review of Anti-Cancer Agents. Journal of Fluorine Chemistry, 127, 303-319.
http://dx.doi.org/10.1016/j.jfluchem.2006.01.011 [6] Muzzalupo, R., Tavano, L. and La Mesa, C. (2013) Alkyl Glucopyranoside-Based Niosomes Containing Methotrexate for Pharmaceutical Applications: Evaluation of Physico-Chemical and Biological Properties. International Journal of Pharmaceutics, 458, 224-229.
http://dx.doi.org/10.1016/j.ijpharm.2013.09.011 [7] Wu, Z.Q., Shah, A., Patel, N. and Yuan, X.D. (2010) Development of Methotrexate Proline Prodrug to Overcome Resistance by MDA-MB-231 Cells. Bioorganic Medicinal Chemistry Letters, 20, 5108-5112.
http://dx.doi.org/10.1016/j.bmcl.2010.07.024 [8] Pectasides, D., Pectasides, E., Papaxoinis, G., Xiros, N., Kamposioras, K., Tountas, N. and Economopoulos, T. (2010) Methotrexate, Paclitaxel, Ifosfamide, and Cisplatin in Poor-Risk Nonseminomatous Germ Cell Tumors. Urologic Oncology: Seminars and Original Investigations, 28, 617-623.
http://dx.doi.org/10.1016/j.urolonc.2008.10.013 [9] Banerjee, D., Mayer-Kuckuk, P., Capiaux, G., Budak-Alpdogan, T., Gorlick, R. and Bertino, J.R. (2002) Novel Aspects of Resistance to Drugs Targeted to Dihydrofolate Reductase and Thymidylate Synthase. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease, 1587, 164-173.
http://dx.doi.org/10.1016/S0925-4439(02)00079-0 [10] Mackey, J.R., Baldwin, S.A., Young, J.D. and Cass, C.E. (1998) Nucleoside Transport and Its Significance for Anticancer Drug Resistance. Drug Resistance Updates, 1, 310-324.
http://dx.doi.org/10.1016/S1368-7646(98)80047-2 [11] Marques, S.M., Enyedy, E.A., Supuran, C.T., Krupenko, N.I., Krupenko, S.A. and Santos, M.A. (2010) Pteridine-Sulfonamide Conjugates as Dual Inhibitors of Carbonic Anhydrases and Dihydrofolate Reductase with Potential Antitumor Activity. Bioorganic & Medicinal Chemistry, 18, 5081-5089.
http://dx.doi.org/10.1016/j.bmc.2010.05.072 [12] Mauritz, R., Peters, J., Priest, D.G., Assaraf, Y.G., Drori, S., Kathmann, I., Noordhuis, P., Bunni, M.A., Rosowsky, A., Schornagel, J.H., Pinedo, H.M. and Jansen, G. (2002) Multiple Mechanisms of Resistance to Methotrexate and Novel Antifolates in Human CCRF-CEM Leukemia Cells and Their Implications for Folate Homeostasis. Biochemical Pharmacology, 63, 105-115.
http://dx.doi.org/10.1016/S0006-2952(01)00824-3 [13] Gangjee, A., Adair, O. and Queener, S.F. (1999) Pneumocystis carinii and Toxoplasma gondii Dihydrofolate Reductase Inhibitors and Antitumor Agents:? Synthesis and Biological Activities of 2,4-Diamino-5-methyl-6-[(monosubstituted anilino)methyl]pyrido[2,3-d]pyrimidines. Journal of Medicinal Chemistry, 42, 2447-2455.
http://dx.doi.org/10.1021/jm990079m [14] Elnagdi, M.H., Al-Awadi, N. and Erian, A.N. (1996) In Compensative Heterocyclic Chemistry II. In: Katritzky, A.R., Rees, C.W. and Scriven, E.F.V., Eds., Pergamon Press, Oxford, 431-488. [15] Rashad, A.E., Mahmoud, A.E. and Ali, M.M. (2011) Synthesis and Anticancer Effects of Some Novel Pyrazolo[3,4-d]-pyrimidine Derivatives by Generating Reactive Oxygen Species in Human Breast Adenocarcinoma Cells. European Journal of Medicinal Chemistry, 46, 1019-1026.
http://dx.doi.org/10.1016/j.ejmech.2011.01.013 [16] Elnagdi, M.H., Elmoghayar, M.R.H. and Elgemeie, G.F. (1987) Chemistry of Pyrazolo-Pyrimidines. Advances in Heterocyclic Chemistry, 41, 319-376.
http://dx.doi.org/10.1016/S0065-2725(08)60164-6 [17] Zatloukal, M., Jorda, R., Gucky, T., Reznícková, E., Voller, J., Pospísil, T., Malínková, V., Adamcová, V., Krystof, V. and Strnad, M. (2013) Synthesis and in Vitro Biological Evaluation of 2,6,9-Trisubstituted Purines Targeting Multiple Cyclin-Dependent Kinases. European Journal of Medicinal Chemistry, 61, 61-72.
http://dx.doi.org/10.1016/j.ejmech.2012.06.036 [18] Kumar, A., Sinha, S. and Chauhan, P.M. (2012) Synthesis of Novel Antimycobacterial Combinatorial Libraries of Structurally Diverse Substituted Pyrimidines by Three Component Solid Phase Reactions. Bioorganic Medicinal Chemistry Letters, 12, 667-669.
http://dx.doi.org/10.1016/S0960-894X(01)00829-0 [19] Baraldi, P.G., Pavani, M.G., Nunez, M., Brigid, P., Vitali, B., Gambari, R. and Romagnoli, R. (2002) Antimicrobial and Antitumor Activity of n-Heteroimmine-1,2,3-dithiazoles and Their Transformation in Triazolo-, Imidazo-, and Pyrazolopirimidines. Bioorganic Medicinal Chemistry, 10, 449-456.
http://dx.doi.org/10.1016/S0968-0896(01)00294-2 [20] Nasr, M.N. and Gineinah, M.M. (2002) Pyrido[2, 3-d]pyrimidines and Pyrimido[5’,4’:5, 6]pyrido[2, 3-d]pyrimidines as New Antiviral Agents: Synthesis and Biological Activity. Archiv der Pharmazie, 335, 289-295.
http://dx.doi.org/10.1002/1521-4184(200208)335:6<289::AID-ARDP289>3.0.CO;2-Z [21] Nagarapu, L., Vanaparthi, S., Bantu, V. and Kumar, C.G. (2013) Synthesis of Novel Benzo[4,5]thiazolo[1,2- a]pyrimi- dine-3-carboxylate Derivatives and Biological Evaluation as Potential Anticancer Agents. European Journal of Medicinal Chemistry, 69, 817-822.
http://dx.doi.org/10.1016/j.ejmech.2013.08.024 [22] Sondhi, S.M., Johar, M., Rajvanshi, S., Dastidar, S.G., Shukla, R., Raghubir, R., et al. (2001) Anticancer, Antiinflammatory and Analgesic Activity Evaluation of Heterocyclic Compounds Synthesized by the Reaction of 4-Isothiocyanato- 4-methylpentan-2-one with Substituted o-Phenylenediamines, o-Diaminopyridine and (Un)Substituted o. Australian Journal of Chemistry, 54, 69-74.
http://dx.doi.org/10.1071/CH00141 [23] Youssif, S. and Assy, M. (1996) Fervenulin, 4-Deazafervenulin and 5-Deazaalloxazines Analogue: Synthesis and Antimicrobial Activity. Journal of Chemical Research, 442, 2546. [24] Herrmann, M., Lorenz, H.M., Voll, R., Grünke, M., Woith, W. and Kalden, J.R. (1994) A Rapid and Simple Method for the Isolation of Apoptotic DNA Fragments. Nucleic Acids Research, 22, 5506-5507.
http://dx.doi.org/10.1093/nar/22.24.5506 [25] Ishikawa, I., Itoh, T., Melik-Ohanjanian, R.G., Takayangi, H., Mizunc, Y. and Ogura, H. (1990) Synthesis and X-Ray Analysis of 1-Benzyl-6-chlorouracil. Heterocycles, 31, 1641-1646.
http://dx.doi.org/10.3987/COM-90-5472 [26] Cresswell, R.M. and Wood, H.C.S. (1960) The Biosynthesis of Pteridines. Part I. The Synthesis of Riboflavin. Journal of the Chemical Society, 4768-4775. [27] Youssif, S. and Pfleiderer, W. (1998) Purines XIV.[1]. Reactivity of 8-Bromo-3,9-dimethylxanthine towards Some Nucleophilic Reagents. Journal of Heterocyclic Chemistry, 35, 949-954.
http://dx.doi.org/10.1002/jhet.5570350428 [28] Youssif, S. (1997) DMF Acetals as Alkylating and Cyclizing Agents: A Facile Route to Substituted Pyrazolo[3,4-d] pyrimidine-4,6(5H,7H)-diones. Chemical Monthly, 128, 493-501.
http://dx.doi.org/10.1007/BF00806857 [29] Hutzenlaub, W. and Pfleiderer, W. (1979) Purines, XIII. Simplified Syntheses of 7-Methy- and 1,7-Dimethylxanthines and Uric Acids. Liebigs Annalen der Chemie, 1847-1854. [30] Youssif, S. (2004) 6-Aminouracil as Precursors for the Synthesis of Fused Di- and Tricyclic Pyrimidines. Journal of Chemical Research, 341-343. [31] Youssif, S. and Ageli, F. (2008) One-Pot Synthesis of Fused 2-Thiouracils: Pyrimidopyrimidines, Pyridopyrimidines and Imidazolopyrimidines. Zeitschrift für Naturforschung, 63b, 860-864. [32] Peet, N.P., Huber, E.W. and Huffman, J.C. (1995) Reaction of Ninhydrin with β-Dicarbonyl Compounds. Journal of Heterocyclic Chemistry, 32, 33-41.
http://dx.doi.org/10.1002/jhet.5570320106 [33] Prabhakar, K.R., Veerapur, V.P., Bansal, P., Vipan, K.P., Reddy, K.M., Barik, A., Reddy, B.K.D., Reddanna, P., Priyadarsini, K.I. and Unnikrishnan, M.K. (2006) Identification and Evaluation of Antioxidant, Analgesic/Anti-Inflammatory Activity of the Most Active Ninhydrin-Phenol Adducts Synthesized. Bioorganic & Medicinal Chemistry, 14, 7113-7120.
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