Synthesis and Anticancer Activities of 5-halogeno Pyrimidine

Synthesis and anticancer Activities of 5-halogeno PyrimidineSOLID STATE MICROWAVE-ASSISTED SYNTHESIS AND ANTICANCER ACTIVITIES OF N-DERIVATIVES OF 5-HALOGENO SUBSTITUTED PYRIMIDINE 2, 4 DIONEBYTAHIRA SAGHIR overturnThis study will report the discount of some substituted 5-halogenated pyrimidine 2,4dione by stuffy and solid state atomise aid methods. Derivitization of 5-halogenated pyrimidine,2,4 dione give predominately N1and N3-subsituted compounds where R whitethorn be the alkyl ,aryl, allyl, acyl, cyclohexenyleetc. 5-halogenated pyrimidine 2,4 dione derivatives represent the late group of anticancer and bacteriacide agents with potential for development of medicinal application. The application of solid state vaporizes to fundamental synthetic thinking is discourteousing up new opportunities for the synthetic chemist by providing new routes. High consumption of chemicals for prolonged time has adverse effecton environment. This is the backbone reason to adopt answer p ut down condition i.e. eco-friendly microwave aid solid state synthetic routes.IntroductionMicrowave diaphysis has emerged as powerful tool for organic entailment. In concern with a promptly expanding applications base, microwave synthesis can be effectively applied to whatever type of chemistry resulting in faster chemical reaction time from minutes to seconds and improved product yield.The environmental protection has become a globular concern and chemical industry is increasingly searching the ways of developing and applying more effectively and environmentally begins strategies for future sustainable growth.An important disclose of present effort towards eco friendly synthesis is aimed at reduction of intake of resultants as in classical procedures. For this purpose in organic synthesis solid support has made a land mark as the reaction can be performed in dry media or solvent free conditions.Further usage of solid support in association with microwave leads to high yield remarkable reaction rate sweetening high catalytic activity with optimum utilization of energy. The solvent slight orgasm provide an opportunity to conduct selective organic in operation(p) group transformation more efficiently and also allows the work to conductin open vessel thus avoiding the risk of high pressure development.5-halogenated pyrimidine 2,4dione is used as an anticancer agent. A major difference between cancer stalls and design electric cells atomic anatomy 18 that the cancer cells divide much more rapidly. Rapidly dividing cells bring a constant new supply of DNA is the nucleoside,deoxythimidine,which is synthesized in the cell by methylation of uridine. Flouro uracil is administrated to a cancer patient as explode of chem separateapy. The body convert it in to flourouridine capitally decreasing DNA synthesis.A total of pyrimidine bases possess anti viral and anti cancer activities. In profit N1and N3-di substituted 5 halogenated pyrimidine2,4dion e also exhibit anticancer , antibacterial and anti fungalactivities. literary works ReviewZeng and his coworkersstudied on activity and structure of co-relation which are useful to medicine breakthrough. By modifying the nature and position of substituent or pyrimidine and theirderivatives, a change in biological activity is observed. The synthesis of organic compound and pharmacological evaluation of these compound deal been set forth by them, they have synthesized large effect of compound using different reaction condition i.e. liquid flesh reaction and solid phase1.Stefeny,PaulaM and their coworkers applied microwave assisted organic synthesis in many formats ranging from traditional solution phase to solvent free reactions2.Verma and Rajender Singh made solvent free synthesis of heterocyclic compounds. They reported that microwave enhanced solvent free synthetic approach has many advantages. These advantages aresimplicity,manipulative comforter of the operation and conse rvation of solvent .A variety of solid state reactions are described that occur rapidly at ambient pressure downstairs solventless conditions and provide ready access to intermediates such(prenominal) as enamines and tosyloxyketones which can be transformed in situ to biologically significant heterocyclic compounds such as isoflav-3-enes, flavones, quinolones, 2-aroylbenzobfurans and thiazoles in one-pot operation. Multi parcel reactions under these solvent-free conditions can be adapted for high expedite parallel synthesis and are exemplified by assembly of dihydropyrimidine-2(1H)-ones (Biginelli reaction) and imidazo1,2-aannulated pyridines, pyrazines and pyrimidines (Ugi reaction) which may have potential in building a library of such compounds3.Verma et al. 2009 show that microwave enhanced solvent free synthatic approach has thefeatures simplicity manipulative ease of the operation and conservation of solvents as the main advantage. This eco friendly approach is found as an application in facile organic operating(a) group transformation is applied to rapid assembly of hetrocyclic compounds4.Filler and Roberts postulated the enormousness of fluore containing compounds synthesis in bio and medicinal chemistry e.g. amino acid,anti canceragents,nucleosides, centeral nervous placement agents and anesthetic agents5.Sugiyama,H,etal.explained 5 iodo uracil containing DNA-zalpha complex showed photo reactivity. For the high lean binding it was observed that NH2 terminusZ-alpha and double strained RNA was very darksome respectively. In the absence the incidence of Z-alpha,to relate the structure of Z-DNA induced by Zalpha,were perceived in comparison to that with high salt concentration,than the hydroxylated product was meritoriously produced in it specified by Z-alpha.6Zhan,etal. have made the solvent and catalyst-free synthesis of dihydropyrimidione in one pot conditions under focused microwave irradiation in 2008.7Andre Loupy has defined microwave chemist ry as the science of applying microwave irradiation to chemical reaction8.In literature we found that initiallyRichard Gedye and coworkers have described the use of microwave irradiation for organic synthesis.After Richard then number of other scientist in the field of organic chemistry reported in fact about various organic reactions which were performed by using this technology. Various reactions in literatureinclude Alkylation,Esterification,Sponification,Condensation ,Oxidation.Reduction.Cycloaddition,Rearrangments,N-acylations,and Olefination.9Kidwai and Rastogi reported an eco friendly approach for the synthesis of 2 substituted-4-6-diarylpyrimidines using inorganic solid supports for its catalytic roleas well as energy transfer strength is described.The methodology eliminates the usage of solvents during reaction.Microwave assisted basic alumina catalysed reaction is the beat out as a catalysis as well as reaction time and yield.10Gedye and Langahave talked about specific microwave effects.11Loupy and coworkershave published a number of rewiews on solvent-free reactions.12Kamal Alannan have reported that substituted uracils especially at 5-position play a key role in many metabolic processes. Uracil reacts with halogens such as,chlorine,Bromine. Iodineflorine to give haogen substituted compounds. From the literature it was found that the halogen substituted uracils are important anticancer drugs.13Zhang and eats reported the major advantage of solvent-free, for the green synthesis derivatives of heterocyclic compounds. The major advantages of this method are simple experimental and work-up procedures, solvent-free reaction conditions, small fare of catalyst and short reaction time, high yield, and utilization of an inexpensive and reclaimable catalyst14Zhao and co-workers reported the advances in the research of pyrimidine derivatives as antitumor drug harmonize to their action on targets.15Chowdhury and shanker describe the recent development in s olvent-free multi component reactions which was the perfect synergy for eco-compatible organic synthesis. The eco-friendly solvent free approach opens up numerous possibilities for conducting rapid organic sunthesis.16Khosrou and Ali reported the cytotoxicity of synthesized dinitrophenyl derivatives of 5-fluorouracil under hypotoxic conditions on HT-29 cell line under both aerobic and hypotoxic conditions.17ObjectivesSolid state microwaves assisted organic synthesis have an impact on drug discovery. The discovery of compounds with improved biological properties can be made more efficient by using new techniques.The objectives of the present research will beSynthesis of new bio active compounds.Method development for synthesis of new bioactive compounds.Characterization of all synthesized compounds.Pharmacological evaluation.Plan of workSynthesis of 5 -halogen substituted pyrimidine 2,4 dione.Synthesis of N-derivatives of 5-halogeno substituted pyrmindine-2,4-dione.Structure elucidat ion will be carried out bya.UV/VIS spectroscopyb.FTIRspectroscopyc.NMRd.Mass spectrometry4.Pharmacological evaluation(anticanceractivities)of synthesized compounds.METHODOLOGYMicrowave- assisted synthesis has been applied in many formats ranging from traditional solution phase to solid phase and solvent free reactions. By using dry conditions, the hazards of volatile organic solvents in microwave oven can be eliminated. The solid state synthesis of N-derivatives of 5-halogen substituted of pyrimidine 2,4 dione is of great interest in present research.PLACE OF WORK1. Lahore College For Women University, Lahore.2.University of Veterinary and living organism Sciences Lahore..References1.Zeng ,J .pharma, Res.16, 304-309, 1999.2.Stafani, H.A Gatti, P.M, Synth.commun.30, 2165-2173,2000.3.Varma, R.S., JournalofHetrocycle.Chem.36, 1565-1571, 1999.4.Verma, R. S., Journal of Heterocyclic Chemistry, 36(6), 1565 1571, 2009.5.Filler,ACS.Symp.Ser,60, 616,3793,2000.6.Oyoshi, T. Sugiyama, H.Journ al of Nucleic Acids Research, (1), 123-4, 2001.7. Zhan, H.WWang, J. X. Journal ofChin.Chem,Lett. 19,1183-1185,2008.8. Loupy, Micro wave in thorough synthesis, Willey-VCH, Weinhein, 2006.9. Gedye, N Smith F.E,Can J. Chem. 66,17, 1887.10. Kidwai, S.Rastogi, Bul and KoreanChen. Soc., 24, 11- 1575, 2003.11. Lang,F. org. synth., 4,373-386, 1997.12. Loupy, A.Synthesis1998.13. Kamal,A Venka, P, J.Chem, soc., Daton Trans, 3381-339,2002.14. Zhang, Y Zhou, Z, Organic chemistry international, 1, 194784-5, 201215. Zhao, P You W, Acta pharmacentica sinica, 47(5)580-7, 201216. Choudhury, S Shankar, M, RSC Adv.2, 4547-4592, 201217. Khosrou, Ali , ISI journal of Bio Chemistry and molecular Biology.27/59, 176/290, 2013