A Novel One-Pot and Efficient Procedure for Synthesis of New Fused Uracil Derivatives for DNA Binding

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.

[1]  C. La Mesa,et al.  Alkyl glucopyranoside-based niosomes containing methotrexate for pharmaceutical applications: evaluation of physico-chemical and biological properties. , 2013, International journal of pharmaceutics.

[2]  C. Ganesh Kumar,et al.  Synthesis of novel benzo[4,5]thiazolo[1,2-a]pyrimidine-3-carboxylate derivatives and biological evaluation as potential anticancer agents. , 2013, European journal of medicinal chemistry.

[3]  A. Ramírez de Molina,et al.  Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells. , 2013, Pharmacological research.

[4]  M. Strnad,et al.  Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases. , 2013, European journal of medicinal chemistry.

[5]  Mamdouh M. Ali,et al.  Synthesis and anticancer effects of some novel pyrazolo[3,4-d]pyrimidine derivatives by generating reactive oxygen species in human breast adenocarcinoma cells. , 2011, European journal of medicinal chemistry.

[6]  T. Economopoulos,et al.  Methotrexate, paclitaxel, ifosfamide, and cisplatin in poor-risk nonseminomatous germ cell tumors. , 2010, Urologic oncology.

[7]  Xudong Yuan,et al.  Development of methotrexate proline prodrug to overcome resistance by MDA-MB-231 cells. , 2010, Bioorganic & medicinal chemistry letters.

[8]  N. Peet,et al.  Reaction of Ninhydrin with β-Dicarbonyl Compounds. , 2010 .

[9]  F. Lévi,et al.  Chronotherapy and the molecular clock: Clinical implications in oncology. , 2010, Advanced drug delivery reviews.

[10]  C. Supuran,et al.  Pteridine-sulfonamide conjugates as dual inhibitors of carbonic anhydrases and dihydrofolate reductase with potential antitumor activity. , 2010, Bioorganic & medicinal chemistry.

[11]  S. Youssif,et al.  One-pot Synthesis of Fused 2-Thiouracils: Pyrimidopyrimidines, Pyridopyrimidines and Imidazolopyrimidines , 2008 .

[12]  G. Rewcastle Pyrimidines and their Benzo Derivatives , 2008 .

[13]  P. Reddanna,et al.  Identification and evaluation of antioxidant, analgesic/anti-inflammatory activity of the most active ninhydrin-phenol adducts synthesized. , 2006, Bioorganic & medicinal chemistry.

[14]  D. O'Hagan,et al.  Fluorine in medicinal chemistry: A review of anti-cancer agents , 2006 .

[15]  S. Youssif 6-Aminouracils as precursors for the syntheses of fused di- and tricyclic pyrimidines , 2004 .

[16]  M. N. Nasr,et al.  Pyrido [2, 3‐d]pyrimidines and Pyrimido[5′, 4′:5, 6]pyrido[2, 3‐d]pyrimidines as New Antiviral Agents: Synthesis and Biological Activity , 2002, Archiv der Pharmazie.

[17]  Debabrata Banerjee,et al.  Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. , 2002, Biochimica et biophysica acta.

[18]  Arun Kumar,et al.  Syntheses of novel antimycobacterial combinatorial libraries of structurally diverse substituted pyrimidines by three-component solid-phase reactions. , 2002, Bioorganic & medicinal chemistry letters.

[19]  P. Brigidi,et al.  Antimicrobial and antitumor activity of N-heteroimmine-1,2,3-dithiazoles and their transformation in triazolo-, imidazo-, and pyrazolopirimidines. , 2002, Bioorganic & medicinal chemistry.

[20]  G. Peters,et al.  Multiple mechanisms of resistance to methotrexate and novel antifolates in human CCRF-CEM leukemia cells and their implications for folate homeostasis. , 2002, Biochemical pharmacology.

[21]  J. Lown,,et al.  Anticancer, Anti-inflammatory 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 , 2001 .

[22]  S. Queener,et al.  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. , 1999, Journal of medicinal chemistry.

[23]  G. Olah,et al.  Acid-Catalyzed Condensations of Ninhydrin with Aromatic Compounds. Preparation of 2,2-Diaryl-1,3-indanediones and 3-(Diarylmethylene)isobenzofuranones1. , 1999, The Journal of organic chemistry.

[24]  W. Eisenreich,et al.  Biosynthesis of Pteridines , 1998, The Journal of Biological Chemistry.

[25]  W. Pfleiderer,et al.  Purines XIV.. Reactivity of 8-bromo-3,9-dimethylxanthine towards some nucleophilic reagents† , 1998 .

[26]  J. Mackey,et al.  Nucleoside transport and its significance for anticancer drug resistance. , 1998, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[27]  S. Youssif DMF acetals as alkylating and cyclizing agents: A facile route to substituted pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-diones , 1997 .

[28]  M. Assy,et al.  Fervenulin, 4‐Deazafervenulin and 5‐Deazaalloxazine Analogues: Synthesis and Antimicrobial Activity. , 1997 .

[29]  H. Lorenz,et al.  A rapid and simple method for the isolation of apoptotic DNA fragments. , 1994, Nucleic acids research.

[30]  H. Wamhoff,et al.  Uracils: Versatile Starting Materials in Heterocyclic Synthesis , 1993 .

[31]  H. Ogura,et al.  Synthesis and X-Ray Analysis of 1-Benzyl-6-chlorouracil. , 1991 .

[32]  H. Ogura,et al.  Synthesis and x-ray analysis of 1-benzyl-6-chlorouracil , 1990 .

[33]  G. Elgemeie,et al.  Chemistry of Pyrazolopyrimidines , 1988 .

[34]  D. J. Brown,et al.  2.13 – Pyrimidines and their Benzo Derivatives , 1984 .

[35]  W. Pfleiderer,et al.  PURINES. XIII. SIMPLIFIED SYNTHESES OF 7-METHYL- AND 1,7-DIMETHYLXANTHINES AND -URIC ACIDS , 1980 .

[36]  G. Brown,et al.  The biosynthesis of pteridines. , 1971, Advances in enzymology and related areas of molecular biology.

[37]  H. Wood,et al.  928. The biosynthesis of pteridines. Part I. The synthesis of riboflavin , 1960 .

[38]  H. Bredereck,et al.  Synthesen in der Purinreihe, VI. Mitteil.1): Synthesen mit 4‐ und 5‐Amino‐uracil , 1955 .

[39]  F. Blicke,et al.  Reactions of 1,3-Dimethyl-5,6-diaminouracil , 1954 .

[40]  J. Ruttink Investigations in the purine series. II. Synthesis of some purine derivatives , 1946 .

[41]  S. Gabriel,et al.  Synthesen in der Purinreihe , 1901 .