Login Register Cart 0
Generic placeholder image

Current Green Chemistry

Editor-in-Chief

ISSN (Print): 2213-3461
ISSN (Online): 2213-347X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Water-Mediated Synthesis, Antibacterial and Antioxidant Evaluation of New Fused Pyrimido-pyrimidine and Pyrimido-purines Derived From Nucleobases

Author(s): Ichrak Bouguessa, Mohamed Aber, Nawal Khier, Mohamed Dehamchia*, Samir Bayou and Zine Régaïnia

Volume 11, Issue 1, 2024

Published on: 04 September, 2023

Page: [75 - 83] Pages: 9

DOI: 10.2174/2213346110666230720152024

Price: $65

conference banner
Abstract

Introduction: A simple and eco-friendly synthesis of novel substituted pyrimido[1,6- a]pyrimidine, pyrimido[1,2-g]purine, and pyrimido[2,1-e]purine was accomplished by refluxing of nucleobases (cytosine, adenine or guanine) and dibenzalacetone (DBA) in water using NaOH as a catalyst.

Methods: The molecular structures of the resulting products were characterized by infrared spectroscopy (FT-IR), mass spectrometry, and proton (1H) and carbon (13C) nuclear magnetic resonance (NMR).

Results: The antibacterial activity of the newly fused heterocycles was assayed against the Gram-positive bacterium Staphylococcus aureus (ATCC 6538) and Gram-negative Escherichia coli (ATCC 8737) using gentamicin as a standard commercially available antibiotic.

Conclusion: In addition, the antioxidant capacity was screened using the 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH•) and the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS+•) radicals scavenging assay.

Keywords: Pyrimidine, purines, dibenzalacetone, green chemistry, antibacterial activity, antioxidant activity.

« Previous
Graphical Abstract

[1]
Holmgren, A.V.; Wenner, W. Alloxan monohydrate. Org. Synth., 1963, 32, 6.
[http://dx.doi.org/10.15227/orgsyn.032.0006]
[2]
Webb, M.E.; Marquet, A.; Mendel, R.R.; Rébeillé, F.; Smith, A.G. Elucidating biosynthetic pathways for vitamins and cofactors. Nat. Prod. Rep., 2007, 24(5), 988-1008.
[http://dx.doi.org/10.1039/b703105j] [PMID: 17898894]
[3]
Kumar, S.; Narasimhan, B. Therapeutic potential of heterocyclic pyrimidine scaffolds. Chem. Cent. J., 2018, 12(1), 38.
[http://dx.doi.org/10.1186/s13065-018-0406-5] [PMID: 29619583]
[4]
Cocco, M.T.; Congiu, C.; Onnis, V.; Piras, R. Synthesis and antitumor evaluation of 6-thioxo-, 6-oxo- and 2,4-dioxopyrimidine derivatives. Farmaco, 2001, 56(10), 741-748.
[http://dx.doi.org/10.1016/S0014-827X(01)01123-5] [PMID: 11718266]
[5]
Abbas, N.; Matada, G.S.P.; Dhiwar, P.S.; Patel, S.; Devasahayam, G. Fused and substituted pyrimidine derivatives as profound anticancer agents. Anticancer. Agents Med. Chem., 2021, 21(7), 861-893.
[http://dx.doi.org/10.2174/18715206MTA48MzYzy] [PMID: 32698738]
[6]
Wu, W.; Lan, W.; Wu, C.; Fei, Q. Synthesis and antifungal activity of pyrimidine derivatives containing an amide moiety. Front Chem., 2021, 9, 695628.
[http://dx.doi.org/10.3389/fchem.2021.695628] [PMID: 34322475]
[7]
Pandey, S.; Suryawanshi, S.N.; Gupta, S.; Srivastava, V.M. Synthesis and antileishmanial profile of some novel terpenyl pyrimidines. Eur. J. Med. Chem., 2004, 39(11), 969-973.
[http://dx.doi.org/10.1016/j.ejmech.2004.03.007] [PMID: 15501546]
[8]
Anupama, B.; Dinda, S.C.; Prasad, Y.R.; Rao, A.V. Synthesis and antimicrobial activity of some new 2,4,6-trisubstituted pyrimidines. Int. J. Res. Pharm. Chem., 2012, 2(2), 231-236.
[9]
Khalifa, N.M.; Abdel-Rahman, A.A.H.; Abd-Elmoez, S.I.; Fathalla, O.A.; Abd El-Gwaad, A.A. A convenient synthesis of some new fused pyridine and pyrimidine derivatives of antimicrobial profiles. Res. Chem. Intermed., 2015, 41(4), 2295-2305.
[http://dx.doi.org/10.1007/s11164-013-1347-1]
[10]
Laddha, S.S.; Bhatnagar, S.P. Novel fused quinazolinones: further studies on the anticonvulsant activity of 1,2,9,11-tetrasubstituted- 7H -thieno[2´,3´:4,5]pyrimido[6,1-b]-quinazolin-7-one and 1,3,10,12-tetrasubstituted- 8H -pyrido[2´,3´:4,5]pyrimido[6,1-b]quinazolin-8-one. Future Med. Chem., 2010, 2(4), 565-573.
[http://dx.doi.org/10.4155/fmc.10.16] [PMID: 21426007]
[11]
Meneghesso, S.; Vanderlinden, E.; Stevaert, A.; McGuigan, C.; Balzarini, J.; Naesens, L. Synthesis and biological evaluation of pyrimidine nucleoside monophosphate prodrugs targeted against influenza virus. Antiviral Res., 2012, 94(1), 35-43.
[http://dx.doi.org/10.1016/j.antiviral.2012.01.007] [PMID: 22306172]
[12]
Kumar, S.; Deep, A.; Narasimhan, B. A review on synthesis, anticancer and antiviral potentials of pyrimidine derivatives. Curr. Bioact. Compd., 2019, 15(3), 289-303.
[http://dx.doi.org/10.2174/1573407214666180124160405]
[13]
Bhalgat, C.M.; Irfan Ali, M.; Ramesh, B.; Ramu, G. Novel pyrimidine and its triazole fused derivatives: Synthesis and investigation of antioxidant and anti-inflammatory activity. Arab. J. Chem., 2014, 7(6), 986-993.
[http://dx.doi.org/10.1016/j.arabjc.2010.12.021]
[14]
Salem, M.S.; Farhat, M.; Errayes, A.O.; Madkour, H.M.F. Antioxidant activity of novel fused heterocyclic compounds derived from tetrahydropyrimidine derivative. Chem. Pharm. Bull., 2015, 63(11), 866-872.
[http://dx.doi.org/10.1248/cpb.c15-00452] [PMID: 26521851]
[15]
Tozkoparan, B.; Ertan, M.; Kelicen, P.; Demirdamar, R. Synthesis and anti-inflammatory activities of some thiazolo[3,2-a]pyrimidine derivatives. Farmaco, 1999, 54(9), 588-593.
[http://dx.doi.org/10.1016/S0014-827X(99)00068-3] [PMID: 10555260]
[16]
Nassar, E.; El-Badry, Y.A.M.; El Kazaz, H. Synthesis, in vivo anti-inflammatory, and in vitro antimicrobial activity of new 5-benzofuranyl fused pyrimidines. Chem. Pharm. Bull., 2016, 64(6), 558-563.
[http://dx.doi.org/10.1248/cpb.c15-00922] [PMID: 27250790]
[17]
Bairagi, K.M.; Younis, N.S.; Emeka, P.M.; Sangtani, E.; Gonnade, R.G.; Venugopala, K.N.; Alwassil, O.I.; Khalil, H.E.; Nayak, S.K. Antidiabetic activity of dihydropyrimidine scaffolds and structural insight by single crystal x-ray studies. Med. Chem., 2020, 16(7), 996-1003.
[http://dx.doi.org/10.2174/1573406416666191227123048] [PMID: 31880253]
[18]
Joshi, G.; Nayyar, H.; Alex, J.M.; Vishwakarma, G.S.; Mittal, S.; Kumar, R. Pyrimidine-fused derivatives: Synthetic strategies and medicinal attributes. Curr. Top. Med. Chem., 2016, 16(28), 3175-3210.
[http://dx.doi.org/10.2174/1568026616666160506145046] [PMID: 27150371]
[19]
Horwitz, J.P.; Chua, J.; Noel, M. Nucleosides. V. The Monomesylates of 1-(2′-Deoxy-β-D-lyxofuranosyl)thymine 1,2. J. Org. Chem., 1964, 29(7), 2076-2078.
[http://dx.doi.org/10.1021/jo01030a546]
[20]
Fischl, M.A.; Richman, D.D.; Grieco, M.H.; Gottlieb, M.S.; Volberding, P.A.; Laskin, O.L.; Leedom, J.M.; Groopman, J.E.; Mildvan, D.; Schooley, R.T.; Jackson, G.G.; Durack, D.T.; King, D. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N. Engl. J. Med., 1987, 317(4), 185-191.
[http://dx.doi.org/10.1056/NEJM198707233170401] [PMID: 3299089]
[21]
Cane, P.A.; Mutimer, D.; Ratcliffe, D.; Cook, P.; Beards, G.; Elias, E.; Pillay, D. Analysis of hepatitis B virus quasispecies changes during emergence and reversion of lamivudine resistance in liver transplantation. Antivir. Ther., 1999, 4(1), 7-14.
[http://dx.doi.org/10.1177/135965359900400101] [PMID: 10682123]
[22]
Vorbrüggen, H.; Ruh-Polenz, C. Synthesis Of Nucleosides. In: Organic Reactions; Wiley, 1999.
[http://dx.doi.org/10.1002/0471264180.or055.01]
[23]
Yoshimura, Y.; Wakamatsu, H.; Natori, Y.; Saito, Y.; Minakawa, N. Glycosylation reactions mediated by hypervalent iodine: Application to the synthesis of nucleosides and carbohydrates. Beilstein J. Org. Chem., 2018, 14, 1595-1618.
[http://dx.doi.org/10.3762/bjoc.14.137] [PMID: 30013687]
[24]
Diekmann, E.; Friedrich, K.; Fritz, H-G. Didesoxy-Ribonucleoside durch Schmelzkondensation. J. Prakt. Chem., 1993, 335, 415-424.
[http://dx.doi.org/10.1002/prac.19933350504]
[25]
Fischer, E.; Helferich, B. Synthetische glucoside der purine. Ber. Dtsch. Chem. Ges., 1914, 47(1), 210-235.
[http://dx.doi.org/10.1002/cber.19140470133]
[26]
Miyaki, M. Shimizu, B. N→N alkyl and glycosyl migration of purines and pyrimidines. III. N→N alkyl and glycosyl migration of purine derivatives. Chem. Pharm. Bull. (Tokyo), 1970, 18(7), 1446-1456.
[http://dx.doi.org/10.1248/cpb.18.1446]
[27]
Kazimierczuk, Z.; Cottam, H.B.; Revankar, G.R.; Robins, R.K. Synthesis of 2′-deoxytubercidin, 2′-deoxyadenosine, and related 2′-deoxynucleosides via a novel direct stereospecific sodium salt glycosylation procedure. J. Am. Chem. Soc., 1984, 106(21), 6379-6382.
[http://dx.doi.org/10.1021/ja00333a046]
[28]
Wittenburg, E. Eine neue synthese von nucleosiden. Z. Chem., 1964, 4(8), 303-304.
[http://dx.doi.org/10.1002/zfch.19640040806]
[29]
Sugiura, Y.; Furuya, S.; Furukawa, Y. Syntheses of N4,2′,3′,5′-tetraacylcytidines from N4-acylcytosines, via condensation with tetraacylribose and transribosylation with acylated purine nucleosides. Chem. Pharm. Bull. (Tokyo), 1988, 36(9), 3253-3256.
[http://dx.doi.org/10.1248/cpb.36.3253]
[30]
Tkachenko, I.G.; Komykhov, S.A.; Musatov, V.I.; Shishkina, S.V.; Dyakonenko, V.V.; Shvets, V.N.; Diachkov, M.V.; Chebanov, V.A.; Desenko, S.M. In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5- a]pyrimidines. Beilstein J. Org. Chem., 2019, 15, 2390-2397.
[http://dx.doi.org/10.3762/bjoc.15.231] [PMID: 31666873]
[31]
Guchhait, S.K.; Madaan, C. Groebke–Blackburn–Bienaymé multicomponent reaction in scaffold-modification of adenine, guanine, and cytosine: Synthesis of aminoimidazole-condensed nucleobases. Tetrahedron Lett., 2011, 52(1), 56-58.
[http://dx.doi.org/10.1016/j.tetlet.2010.10.143]
[32]
Bizzarri, B.M.; Fanelli, A.; Botta, L.; De Angelis, M.; Palamara, A.T.; Nencioni, L.; Saladino, R. Aminomalononitrile inspired prebiotic chemistry as a novel multicomponent tool for the synthesis of imidazole and purine derivatives with anti-influenza A virus activity. RSC Advances, 2021, 11(48), 30020-30029.
[http://dx.doi.org/10.1039/D1RA05240C] [PMID: 35480240]
[33]
Cortes-Clerget, M.; Yu, J.; Kincaid, J.R.A.; Walde, P.; Gallou, F.; Lipshutz, B.H. Water as the reaction medium in organic chemistry: From our worst enemy to our best friend. Chem. Sci. (Camb.), 2021, 12(12), 4237-4266.
[http://dx.doi.org/10.1039/D0SC06000C] [PMID: 34163692]
[34]
Faisal, M. Water in Organic Synthesis as a Green Solvent. In: Industrial Applications of Green Solvents I; Materials Research Foundations, 2019; 50, pp. 61-106.
[http://dx.doi.org/10.21741/9781644900239-3]
[35]
Laird, T. Organic synthesis in water; Blackie/Thomson Science: London, UK, 1998.
[36]
Kumaravel, K.; Vasuki, G. Multi-component reactions in water. Curr. Org. Chem., 2009, 13(18), 1820-1841.
[http://dx.doi.org/10.2174/138527209789630514]
[37]
Zhou, F.; Hearne, Z.; Li, C.J. Water—the greenest solvent overall. Curr. Opin. Green Sustain. Chem., 2019, 18, 118-123.
[http://dx.doi.org/10.1016/j.cogsc.2019.05.004]
[38]
Synthesis of dibenzalacetone, organic syntheses. Coll. Vol., 1943, 2, 167. Dibenzalacetone. Org. Synth., 1932, 12, 22.
[http://dx.doi.org/10.15227/orgsyn.012.0022]
[39]
Ibrahim, M.N.; Al-Difar, H.A. Synthesis and biological activity study of some heterocycles derived from dibenzalacetone. Int. J. Eng. Sci., 2013, 2(3), 57-63.
[40]
Bauer, A.W.; Perry, D.M.; Kirby, W.M. Single-disk antibiotic-sensitivity testing of staphylococci; An analysis of technique and results. AMA Arch. Intern. Med., 1959, 104(2), 208-216.
[http://dx.doi.org/10.1001/archinte.1959.00270080034004] [PMID: 13669774]
[41]
Bauer, A.W.; Kirby, W.M.M.; Sherris, J.C.; Turck, M. Antibiotic susceptibility testing by a standardized single disk method. Am. J. Clin. Pathol., 1966, 45(4_ts), 493-496.
[http://dx.doi.org/10.1093/ajcp/45.4_ts.493] [PMID: 5325707]
[42]
Perez, C.; Paul, M.; Bazerque, P. An Antibiotic assay by the agar-well diffusion method. Acta Biol. Med. Exp., 1990, 15, 113-115.
[43]
Volleková, A. Košťálová, D.; Sochorová, R. Isoquinoline alkaloids from Mahonia aquifolium stem bark are active againstMalassezia spp. Folia Microbiol., 2001, 46(2), 107-111.
[http://dx.doi.org/10.1007/BF02873586] [PMID: 11501395]
[44]
Sidney, M.F.; Williaiam, J.M.; Elvyn, G.S. Baily & Scotts Microbiology; C. V. Moshy: St. Louis, 1978, pp. 385-403.
[45]
Brand-Williams, W.; Cuvelier, M.E.; Berset, C. Use of a free radical method to evaluate antioxidant activity. Lebensm. Wiss. Technol., 1995, 28(1), 25-30.
[http://dx.doi.org/10.1016/S0023-6438(95)80008-5]
[46]
Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med., 1999, 26(9-10), 1231-1237.
[http://dx.doi.org/10.1016/S0891-5849(98)00315-3] [PMID: 10381194]

Rights & Permissions Print Cite
Article Metrics
16
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy