Evaluation of antibacterial and antifungal activities of N-benzylthienopyrimidinone derivatives

Authors

  • Adama DIEDHIOU Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Mamadou BALDE Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Idrissa NDOYE Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Mouhamadou THIAM Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Harouna TIRERA Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Abdoulaye DIOP Laboratoire de Bactériologie-Virologie du CHU Aristide Le Dantec, Dakar, Senegal
  • Rokhaya Sylla GUEYE Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Yoro TINE Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Assane DIENG Laboratoire de Bactériologie-Virologie du CHU Aristide Le Dantec, Dakar, Senegal
  • Samba Fama NDOYE Department of Chemistry, Faculty of Sciences and Technologies, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Insa SECK Department of Chemistry, Faculty of Sciences and Technologies, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Matar SECK Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Alassane WELE Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Djibril FALL Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal
  • Denis GRAVIER Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France
  • Martine LEMBEGE Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France
  • Géneviève HOU Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France
  • Isabelle BESTEL Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

Abstract

This study is part of the biological investigation of the chemical library of molecules already described by the Laboratory of Organic Chemistry and Therapeutic Chemistry of the University of Bordeaux. The main objective was to explore the contribution of a thienyl moiety attached to the pyrimidinone nucleus, in the expression of an antimicrobial activity.

The structural modifications mainly concerned the conservation or not of  the  benzo fragment attached to the thienyl, the saturation or not in position-1,2 of the pyrimidinone ring, the substitution on N-benzyl with more or less lipophilic units, the modification of the orientation of the thienyl fragment with, on  the one hand, the compounds in which the sulfur is located near the N1 nitrogen (series of thieno[2,3-d]pyrimidin-4-ones) and on the other hand, compounds in which the sulfur is located near the ketone group (series of thieno[3,2-d]pyrimidin-4-ones).

In general, thienyl fragment with sulfur located near the ketone group and the unsaturated pyrimidinone nucleus in the 1,2-position, seem to promote a broad spectrum of antibacterial activity, with compound 9c which is active on both Gram + bacteria and Gram – bacteria studied. The same pattern was observed for antifungal activity, which is maximum with the compounds of the thieno[3,2-d]pyrimidin-4-ones series for an MIC of 31.25 μg/ml on the strains of Candida albicans and Candida kruzei studied.

Keywords: Thienopyrimidinones, antibacterial activity, antifungal activity.

Keywords:

Thienopyrimidinones, antibacterial activity, antifungal activity

DOI

https://doi.org/10.22270/jddt.v12i3.5449

Author Biographies

Adama DIEDHIOU, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

Mamadou BALDE, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Idrissa NDOYE, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Mouhamadou THIAM, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Harouna TIRERA, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Abdoulaye DIOP, Laboratoire de Bactériologie-Virologie du CHU Aristide Le Dantec, Dakar, Senegal

Laboratoire de Bactériologie-Virologie du CHU Aristide Le Dantec, Dakar, Senegal

Rokhaya Sylla GUEYE, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Yoro TINE, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Assane DIENG, Laboratoire de Bactériologie-Virologie du CHU Aristide Le Dantec, Dakar, Senegal

Laboratoire de Bactériologie-Virologie du CHU Aristide Le Dantec, Dakar, Senegal

Samba Fama NDOYE, Department of Chemistry, Faculty of Sciences and Technologies, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Department of Chemistry, Faculty of Sciences and Technologies, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Insa SECK, Department of Chemistry, Faculty of Sciences and Technologies, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Department of Chemistry, Faculty of Sciences and Technologies, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Matar SECK, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Alassane WELE, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Djibril FALL, Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Laboratory of Organic Chemistry and Therapeutic Chemistry, FPMO, Cheikh Anta Diop University of Dakar, BP 5005 Dakar-Fann, Senegal

Denis GRAVIER, Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

Martine LEMBEGE, Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

Géneviève HOU, Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

Isabelle BESTEL, Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

Laboratory of Organic Chemistry and Therapeutic Chemistry, UFR SP, University of Bordeaux, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France

References

Sharma V, Chitranshi N, Agarwal AK. Significance and Biological Importance of Pyrimidine in the Microbial World. Int J Med Chem. 2014; 2014:1-31. https://doi.org/10.1155/2014/202784

Ju Y, Varma RS. Aqueous N-heterocyclization of primary amines and hydrazines with dihalides: Microwave-assisted syntheses of N-azacycloalkanes, isoindole, pyrazole, pyrazolidine, and phthalazine derivatives. J Org Chem. 2006; 71(1):135-141. https://doi.org/10.1021/jo051878h

Ju Y, Kumar D, Varma RS. Revisiting nucleophilic substitution reactions: Microwave-assisted synthesis of azides, thiocyanates, and sulfones in an aqueous medium. J Org Chem. 2006; 71(17):6697-6700. https://doi.org/10.1021/jo061114h

Jain KS, Chitre TS, Miniyar PB, et al. Biological and medicinal significance of pyrimidines. Curr Sci. 2006; 90(6):793-803. https://doi.org/10.1016/j.ejmech.2014.10.085

Bhat AR. Biological Activity of Pyrimidine Derivativies : A Review. 2017:1-4. https://doi.org/10.19080/omcij.2017.01.555565

Modi VS, Basuri TS. The physiological and medicinal potential pyrimidines & different scheme to synthesize pyrimidine heterocycles: An update. Int J Pharm Pharm Sci. 2011; 3(SUPPL. 5):13-25.

Deshpande AN, Dhawale SC. Design, Synthesis, Characterization and Antimicrobial Evaluation of Novel 2,4-Disubstituted Quinazoline Derivatives. J Chem Pharm Res. 2017; 9(2):74-84. http://www.jocpr.com/articles/design-synthesis-characterization-and-antimicrobial-evaluation-of-novel-24disubstituted-quinazoline-derivatives.pdf.

Beale JM, Block JH. Organic Medicinal and Pharmaceutical Chemistry. (Troy DB, ed.).; 2011.

Al Safarjalani ON, Zhou XJ, Rais RH, et al. 5-(Phenylthio)acyclouridine: A powerful enhancer of oral uridine bioavailability: Relevance to chemotherapy with 5-fluorouracil and other uridine rescue regimens. Cancer Chemother Pharmacol. 2005; 55(6):541-551. https://doi.org/10.1007/s00280-004-0967-y

SKOLD O. Enzymic ribosidation and ribotidation of 5-fluorouracil by extracts of the Ehrlich-ascites tumor. Biochim Biophys Acta. 1958; 29(3):651. http://www.ncbi.nlm.nih.gov/pubmed/13584375. https://doi.org/10.1016/0006-3002(58)90029-5

Heidelberger C, Danenberg P V, Moran RG. Fluorinated pyrimidines and their nucleosides. Adv Enzymol Relat Areas Mol Biol. 1983; 54:58-119. http://www.ncbi.nlm.nih.gov/pubmed/6189380.

Kappe CO, Shishkin O V, Uray G, Verdino P. X-ray structure, conformational analysis, enantioseparation, and determination of absolute configuration of the mitotic kinesin Eg5 inhibitor monastrol. Tetrahedron. 2000; 56(13):1859-1862. https://doi.org/10.1016/S0040-4020(00)00116-2

Hijiya T, Yamashita K, Kojima M, et al. An economical synthesis of famciclovir. Nucleosides Nucleotides. 1999; 18(4-5):653-654. http://www.ncbi.nlm.nih.gov/pubmed/10432659. https://doi.org/10.1080/15257779908041530

Kim D-K, Lee N, Ryu DH, et al. Synthesis and evaluation of 2-Amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purines and 2-Amino-9-(3-alkoxycarbonyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purines as potential prodrugs of penciclovir. Bioorg Med Chem. 1999; 7(8):1715-1725. https://doi.org/10.1016/S0968-0896(99)00086-3

Nomoto S, Teshima T, Wakamiya T, Shiba T. The revised structure of capreomycin. J Antibiot (Tokyo). 1977; 30(11):955-959. https://doi.org/10.7164/antibiotics.30.955

Polak A, Scholer HJ. Mode of action of 5-fluorocytosine and mechanisms of resistance. Chemotherapy. 1975; 21(3-4):113-130. https://doi.org/10.1159/000221854

Collins CH, Lyne PM, Grange JM, Falkinhamn III JO. Collins and Lyne's Microbiological Methods. Eighth Edi. Oxford: Arnold; 2004. http://mmstcchemistry.weebly.com/uploads/2/4/1/2/24121933/microbiological_methods.pdf.

Cowman AF, Morry MJ, Biggs BA, Cross GA, Foote SJ. Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum. Proc Natl Acad Sci U S A. 1988. 85(23):9109-9113. http://www.ncbi.nlm.nih.gov/pubmed/3057499. https://doi.org/10.1073/pnas.85.23.9109

Gatton ML, Martin LB, Cheng Q. Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother. 2004; 48(6):2116-2123. https://doi.org/10.1128/AAC.48.6.2116-2123.2004

Barlin G, Kotecka B, Rieckmann K. Potential Antimalarials. XXII. Some 2,4-Diamino-5-(3- and 4-trifluoromethylphenyl and 3,4-methylenedioxyphenyl)pyrimidines. Aust J Chem. 1996; 49(6):647-650. https://doi.org/10.1071/CH9960647

Sardarian A, Douglas KT, Read M, et al. Pyrimethamine analogs as strong inhibitors of double and quadruple mutants of dihydrofolate reductase in human malaria parasites. Org Biomol Chem. 2003; 1(6):960-964. http://www.ncbi.nlm.nih.gov/pubmed/12929634. https://doi.org/10.1039/b211636g

Sirichaiwat C, Intaraudom C, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y. Target Guided Synthesis of 5-Benzyl-2,4-diamonopyrimidines: Their Antimalarial Activities and Binding Affinities to Wild Type and Mutant Dihydrofolate Reductases from Plasmodium falciparum. J Med Chem. 2004; 47(2):345-354. https://doi.org/10.1021/jm0303352

Hidalgo-Zarco F, Gonzalez-Pacanowska D. Trypanosomal dUTPases as potential targets for drug design. Curr Protein Pept Sci. 2001; 2(4):389-397. https://doi.org/10.2174/1389203013381026

Mc Carthy OK, Schipani A, Buendía AM, et al. Design, synthesis and evaluation of novel uracil amino acid conjugates for the inhibition of Trypanosoma cruzi dUTPase. Bioorg Med Chem Lett. 2006; 16(14):3809-3812. https://doi.org/10.1016/j.bmcl.2006.04.027

Suryawanshi SN, Bhat BA, Pandey S, Chandra N, Gupta S. Chemotherapy of leishmaniasis. Part VII: Synthesis and bioevaluation of substituted terpenyl pyrimidines. Eur J Med Chem. 2007; 42(9):1211-1217. https://doi.org/10.1016/j.ejmech.2006.10.002

Singh BK, Mishra M, Saxena N, et al. Synthesis of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines as a new class of antifilarial agents. Eur J Med Chem. 2008; 43(12):2717-2723. https://doi.org/10.1016/j.ejmech.2008.01.038

Rao NV. an Overview on Synthesis and Biological Activity of Pyrimidines. Int J Pharm Chem Res. 2278; 8700(1):14-22. http://www.academia.edu/22763400/An_Overview_On_Synthesis_And_Biological_Activity_Of_Pyrimidines. Accessed August 15, 2017.

Diedhiou A., Fall D., Wele A., Lembège M., Gravier D., Hou G., Daulouède S., Vincendeau P., Mouray É., Grellier P., Nuhrich A. Nouvelles investigations biologiques de benzylquinazolinones et de leurs dérivés réduits. Bull Soc Pharm Bord. 2015; 154(1-4):7-20.

Sircar B, Mandal S. Highlights on the alternatives to antibiotic therapy against bacterial infection. J Drug Deliv Ther. 2021; 11(2):194-203. https://doi.org/10.22270/jddt.v11i2.4596

J.P. Dupin, R.J. Gryglewski, D. Gravier GH, F. Casadebaig, J. Swies SC. Synthesis and thrombolytic activity of new thienopyrimidinone derivatives. J Physiol Pharmacol. 2002:625-634.

Pédeboscq S, Gravier D, Casadebaig F, et al. Synthesis and study of antiproliferative activity of novel thienopyrimidines on glioblastoma cells. Eur J Med Chem. 2010; 45(6):2473-2479. https://doi.org/10.1016/j.ejmech.2010.02.032

Ali EMH, Abdel-Maksoud MS, Oh CH. Thieno[2,3-d]pyrimidine as a promising scaffold in medicinal chemistry: Recent advances. Bioorganic Med Chem. 2019; 27(7):1159-1194. https://doi.org/10.1016/j.bmc.2019.02.044

Biemer JJ. Antimicrobial susceptibility testing by the Kirby-Bauer disc diffusion method. Ann Clin Lab Sci. 1973; 3(2):135-140.

Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically ; Approved Standard - Ninth Edition. Vol 32.; 2012.

Kanawade SB, Toche RB, Rajani DP. Synthetic tactics of new class of 4-aminothieno[2,3-d]pyrimidine-6- carbonitrile derivatives acting as antimicrobial agents. Eur J Med Chem. 2013; 64:314-320. https://doi.org/10.1016/j.ejmech.2013.03.039

Hafez HN, Hussein HAR, El-Gazzar ARBA. Synthesis of substituted thieno[2,3-d]pyrimidine-2,4-dithiones and their S-glycoside analogues as potential antiviral and antibacterial agents. Eur J Med Chem. 2010; 45(9):4026-4034. https://doi.org/10.1016/j.ejmech.2010.05.060

Gaudy C, Buxeraud J. Antibiotiques: Pharmacologie et Thérapeutique. (Elsevier, ed.). Collection Pharma; 2005

Published

15-05-2022
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1.
DIEDHIOU A, BALDE M, NDOYE I, THIAM M, TIRERA H, DIOP A, et al. Evaluation of antibacterial and antifungal activities of N-benzylthienopyrimidinone derivatives. J. Drug Delivery Ther. [Internet]. 2022 May 15 [cited 2025 Mar. 18];12(3):25-30. Available from: https://jddtonline.info/index.php/jddt/article/view/5449

Issue

Vol. 12 No. 3 (2022): Volume 12, Issue 3, May-June 2022

Section

Research

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How to Cite

1.
DIEDHIOU A, BALDE M, NDOYE I, THIAM M, TIRERA H, DIOP A, et al. Evaluation of antibacterial and antifungal activities of N-benzylthienopyrimidinone derivatives. J. Drug Delivery Ther. [Internet]. 2022 May 15 [cited 2025 Mar. 18];12(3):25-30. Available from: https://jddtonline.info/index.php/jddt/article/view/5449
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