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Chemically Modified Uridine Molecules Incorporating Acyl Residues to Enhance Antibacterial and Cytotoxic Activities

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DOI: 10.4236/ijoc.2015.54023    4,632 Downloads   5,409 Views   Citations


A new N-acetylsulfanilylation series of uridine have been synthesized in good yield using direct acylation method and afforded the 5’-O-N-acetylsulfanilyluridine. In order to obtain newer products, the 5’-O-N-acetylsulfanilyluridine derivative was further transformed to a series of 2’,3’-di-O-acyl derivatives containing a wide variety of functionalities in a single molecular framework. The chemical structures of the newly synthesized compounds were confirmed on the basis of their FTIR, 1H-NMR spectroscopy, physicochemical properties and elemental analysis. All the synthesized uridine derivatives were tested for their in vitro antibacterial activity against six human pathogenic bacterial strains and for comparison standard antibiotic Ampicillin was also determined. The study revealed that the selectively acylated deriva-tives 5’-O-N-acetylsulfanilyl-2’,3’-di-O-lauroyluridine and 5’-O-N-acetylsulfanilyl-2’,3’-di-O-pivaloyluridine showed highest inhibition against Staphylococcus aureus and Bacillus cereus, respectively. We also observed that the introduction of hexanoyl, decanoyl, lauroyl, myristoyl and pivaloyl groups, the antibacterial functionality of the compound uridine increases. Another noteworthy observation was that the uridine derivatives were found comparatively more effective against Gram-positive microorganisms than those of Gram-negative microorganisms. In addition, the test chemicals were also tested for cyto-toxicity by brine shrimp lethality bioassay and compounds showed different rate mortality with different concentrations.

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The authors declare no conflicts of interest.

Cite this paper

Kawsar, S. , Ara, H. , Uddin, S. , Hossain, M. , Chowdhury, S. , Sanaullah, A. , Manchur, M. , Hasan, I. , Ogawa, Y. , Fujii, Y. , Koide, Y. and Ozeki, Y. (2015) Chemically Modified Uridine Molecules Incorporating Acyl Residues to Enhance Antibacterial and Cytotoxic Activities. International Journal of Organic Chemistry, 5, 232-245. doi: 10.4236/ijoc.2015.54023.


[1] Wen, J. and Xia, Y. (2012) Adenosine Signaling: Good or Bad in Erectile Function. Arteriosclerosis, Thrombosis, and Vascular Biology, 32, 845-850.
[2] Jordheim, L.P., Durantel, D., Zoulim, F. and Dumontet, C. (2013) Advances in the Development of Nucleoside and Nucleotide Analogues for Cancer and Viral Diseases. Nature Reviews Drug Discovery, 12, 447-464.
[3] Carlezon Jr., W.A., Mague, S.D., Parow, A.M., Stoll, A.L., Cohen, B.M. and Renshaw, P.F. (2005) Antidepressant- Like Effects of Uridine and Omega-3 Fatty Acids Are Potentiated by Combined Treatment in Rats. Biological Psychiatry, 57, 343-350.
[4] Jonas, D.A., Elmadfa, I., Engel, K.H., Heller, K.J., Kozianowski, G., Konig, A., Muller, D., Narbonne, J.F., Wackemagel, W. and Kleiner, J. (2001) Safety Considerations of DNA in Food. Annals of Nutrition & Metabolism, 45, 235-254.
[5] WHO (2004) The Global Burden of Disease Update. World Health Organization.
[6] Williams, J.M. and Richardson, A.C. (1967) Selective Acylation of Pyranosides-I. Benzoylation of Methyl α-D-Gly- copyranosides of Mannose, Glucose and Galactose. Tetrahedron, 23, 1369-1378.
[7] Hiroyuki, H., Horoshi, A., Hiromichi, T. and Tadashi, M. (1990) Introduction of an Alkyl Group into the Sugar Portion of Uracilnucleosides by the Use of Gilman Reagents. Chemical & Pharmaceutical Bulletin, 38, 355-360.
[8] Willard, J.J., Brimacombe, J.S. and Brueton, R.P. (1964) The Synthesis of 3-O-[(benzylthio)carbonyl]-β-D-Glucopy- ranose and Methyl 2,4,6-tri-O-α and β-D-Glucopyranosides. Canadian Journal of Chemistry, 42, 2560-2567.
[9] Wagner, D., Verheyden, J.P.H. and Moffatt, J.G. (1974) Preparation and Synthetic Utility of Some Organotin Derivatives of Nucleosides. Journal of Organic Chemistry, 39, 24-30.
[10] Kim, S., Chang, H. and Kim, W. (1985) Regioselective Acylation of Some Glycopyranoside Derivatives. Journal of Organic Chemistry, 50, 1751-1752.
[11] Kabir, A.K.M.S., Dutta, P. and Anwar, M.N. (2005) Synthesis of Some New Derivatives of D-Mannose. Chittagong University Journal of Science, 29, 1-8.
[12] Ichinari, M., Nakayama, K. and Hayase, Y. (1988) Synthesis of 2,4-Dioxoimidazolidines from 2-Arylimino-1,3-thiaz- ines and Their Antifungal Activity. Heterocycles, 27, 2635-2641.
[13] Gawande, N.G. and Shingare, M.S. (1987) Synthesis of Some Thiazolylthiosemicarbazides, Triazoles, Oxazoles, Thiadiazoles & Their Microbial Activity. Indian Journal of Chemistry, 26, 387-394.
[14] Gupta, R., Paul, S., Gupta, A.K., Kachroo, P.L. and Bani, S. (1997) Synthesis and Biological Activities of Some 2-Substituted Phenyl-3-(3-alkyl/aryl-5,6-dihydro-s-triazolo[3,4-b][1,3,4]thiazolo-6-yl)-indoles. Indian Journal of Chemistry, 36, 707-710.
[15] Singh, H., Shukla, K.N., Dwivedi, R. and Yadav, L.D.S. (1990) Cycloaddition of 4-Amino-3-mercapto-1,2,4-triazole to Heterocumulenes and Antifungal Activity of the Resulting 1,2,4-Triazolo[3,4-c]-1,2-dithia-4,5-diazines. Journal of Agricultural & Food Chemistry, 38, 1483-1486.
[16] Kawsar, S.M.A., Islam, M.M., Chowdhury, S.A., Hasan, T., Hossain, M.K., Manchur, M.A. and Ozeki, Y. (2013) Design and Newly Synthesis of Some 1,2-O-isopropylidene-α-D-glucofuranose Derivatives: Characterization and Antibacterial Screening Studies. Hacettepe Journal of Biology and Chemistry, 41, 195-206.
[17] Kawsar, S.M.A., Faruk, M.O., Rahman, M.S., Fujii, Y. and Ozeki, Y. (2014) Regioselective Synthesis, Characterization and Antimicrobial Activities of Some New Monosaccharide Derivatives. Scientia Pharmaceutica, 82, 1-20.
[18] Kabir, A.K.M.S., Matin, M.M. and Kawsar, S.M.A. (1998) Synthesis and Antibacterial Activities of Some Uridine Derivatives. Chittagong University Journal of Science, 22, 13-18.
[19] Kabir, A.K.M.S., Kawsar, S.M.A., Bhuiyan, M.M.R. and Hossain, S. (2003) Synthesis and Characterization of Some Uridine Derivatives. Journal of Bangladesh Chemical Society, 16, 6-14.
[20] Kawsar, S.M.A., Ferdous, J., Mostafa, G. and Manchur, M.A. (2014) A Synthetic Approach of D-Glucose Derivatives: Spectral Characterization and Antimicrobial Studies. Chemistry & Chemical Technology, 8, 19-27.
[21] Kawsar, S.M.A., Kabir, A.K.M.S., Bhuiyan, M.M.R., Ferdous, J. and Rahman, M.S. (2013) Synthesis, Characterization and Microbial Screening of Some New Methyl 4,6-O-(4-methoxybenzylidene)-α-D-glucopyranoside Derivatives. Journal of Bangladesh Academy of Sciences, 37, 145-158.
[22] Kawsar, S.M.A., Kabir, A.K.M.S., Manik, M.M., Hossain, M.K. and Anwar, M.N. (2012) Antibacterial and Mycelial Growth Inhibition of Some Acylated Derivatives of D-Glucopyranoside. International Journal of Bioscience, 2, 66-73.
[23] Kabir, A.K.M.S., Kawsar, S.M.A., Bhuiyan, M.M.R., Rahman, M.S. and Chowdhury, M.E. (2009) Antimicrobial Screening Studies of Some Derivatives of Methyl α-D-Glucopyranoside. Pakistan Journal of Scientific and Industrial Research, 52, 138-142.
[24] Kabir, A.K.M.S., Kawsar, S.M.A., Bhuiyan, M.M.R. and Banu, B. (2008) Synthesis of Some New Derivatives of Methyl 4,6-O-cyclohexylidene-α-D-glucopyranoside. Journal of Bangladesh Chemical Society, 21, 72-80.
[25] Kabir, A.K.M.S., Kawsar, S.M.A., Bhuiyan, M.M.R., Islam, M.R. and Rahman, M.S. (2004) Biological Evaluation of Some Mannopyranoside Derivatives. Bulletin of Pure & Applied Sciences, 23, 83-91.
[26] Bauer, A.W., Kirby, W.M.M., Sherris, J.C. and Turck, M. (1966) Antibiotic Susceptibility Testing by a Standardized Single Disc Method. American Journal of Clinical Pathology, 45, 493-496.
[27] Miah, M.A.T., Ahmed, H.U., Sharma, N.R., Ali, A. and Miah, S.A. (1990) Antifungal Activity of Some Plant Extracts. Bangladesh Journal of Botany, 19, 5-10.
[28] McLaughlin, J.L. (1991) In: Hostettmann, K., Ed., Methods in Plant Biochemistry: Assays for Bioactivity, Vol. 1, Academic Press, London, 1-31.
[29] Loss, A. and Lutteke, T. (2015) Using NMR Data on In: Lütteke, T. and Frank, M., Eds., Glycoinformatics, Methods in Molecular Biology, Vol. 1273, Springer, New York, 87-95.
[30] Brauer, B., Pincu, M., Buch, V., Bar, I., Simons, J.P. and Gerber, R.B. (2011) Vibrational Spectra of α-Glucose, β-Glucose, and Sucrose: Anharmonic Calculations and Experiment. The Journal of Physical Chemistry A, 115, 5859- 5872.
[31] Kawsar, S.M.A., Khaleda, M., Asma, R., Manchur, M.A., Koide, Y. and Ozeki, Y. (2015) Infrared, 1H-NMR Spectral Studies of some Methyl 6-O-myristoyl-α-D-glucopyranoside Derivatives: Assessment of Antimicrobial Effects. International Letters of Chemistry, Physics and Astronomy, 58, 122-136.
[32] Kawsar, S.M.A., Faruk, M.O., Mostafa, G. and Rahman, M.S. (2014) Synthesis and Spectroscopic Characterization of Some Novel Acylated Carbohydrate Derivatives and Evaluation of Their Antimicrobial Activities. Chemistry & Biology Interface, 4, 37-47.
[33] Kawsar, S.M.A., Hasan, T., Chowdhury, S.A., Islam, M.M., Hossain, M.K. and Manchur, M.A. (2013) Synthesis, Spectroscopic Characterization and in Vitro Antibacterial Screening of Some D-Glucose Derivatives. International Journal of Pure and Applied Chemistry, 8, 125-135.
[34] Kawsar, S.M.A., Kabir, A.K.M.S., Bhuiyan, M.M.R., Siddiqa, A. and Anwar, M.N. (2012) Synthesis, Spectral and Antimicrobial Screening Studies of Some Acylated D-Glucose Derivatives. Rajiv Gandhi University of Health Sciences (RGUHS) Journal of Pharmaceutical Sciences, 2, 107-115.
[35] Kabir, A.K.M.S., Kawsar, S.M.A., Bhuiyan, M.M.R., Rahman, M.S. and Banu, B. (2008) Biological Evaluation of Some Octanoyl Derivatives of Methyl 4,6-O-cyclohexylidene-α-D-glucopyranoside. The Chittagong University Journal of Biological Science, 3, 53-64.
[36] Kim, Y.M., Farrah, S. and Baney, R.H. (2007) Structure-Antimicrobial Activity Relationship for Silanols, a New Class of Disinfectants, Compared with Alcohols and Phenols. International Journal of Antimicrobial Agents, 29, 217-222.
[37] Hunt, W.A. (1975) The Effects of Aliphatic Alcohols on the Biophysical and Biochemical Correlates of Membrane Function. Advances in Experimental Medicine and Biology, 56, 195-210.
[38] Judge, V., Narasimhan, B., Ahuja, M., Sriram, D., Yogeeswari, P., Clercq, E.D., Pannecouque, C. and Balzarini, J. (2013) Synthesis, Antimycobacterial, Antiviral, Antimicrobial Activity and QSAR Studies of N2-Acyl Isonicotinic Acid Hydrazide Derivatives. Medicinal Chemistry, 9, 53-76.

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