Synthesis and antimicrobial evaluation of some 6-aryl-5-cyano-2-thiouracil derivatives

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Synthesis and antimicrobial evaluation of some 6-aryl-5-cyano-2-thiouracil derivatives

A series of 6-aryl-5-cyano-2-thiouracil derivatives (1a-d) was synthesized by the reaction of ethyl cyanoacetate with thiourea and aldehydes. These products were used as intermediate compounds for the synthesis of a number of thiouracil derivatives (2a-d to 10a-d). All compounds were screened for antibacterial and antifungal activities. Some of the prepared compounds, 6-(4-fluorophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide (2a), 4-oxo-2-thioxo-6-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide (2d), 6-(4-fluorophenyl)-4-hydrazino-2-thioxo-1,2-dihydropyrimidine-5-cabonitrile (7a) and 4-hydrazino-2-thioxo-6-(3,4,5-trimethoxyphenyl)-1,2-dihydropyrimidine-5-carbonitrile (7d) revealed promising antimicrobial activity.

Sinteza i antimikrobno vrednovanje nekoliko 6-aril-5-cijano-2-tiouracil derivata

Polazeći iz etil-cijanoacetata, tiouree i odgovarajućeg aldehida sintetizirana je serija 6-aril-5-cijano-2-tiouracil derivata (1a-d), koji su potom upotrijebljeni za dobivanje tiouracil derivata (2a-d do 10a-d). Svim spojevima ispitano je antibakterijsko i antimikotsko djelovanje. Neki od sintetiziranih spojeva, 6-(4-fluorofenil)-4-okso-2-tiokso-1,2,3,4-tetrahidropirimidin-5-karboksamid (2a), 4-okso-2-tiokso-6-(3,4,5-trimetoksifenil)-1,2,3,4-tetrahidropirimidin-5-karboksamid (2d), 6-(4-fluorofenil)-4-hidrazino-2-tiokso-1,2-dihidropirimidin-5-kabonitril (7a) i 4-hidrazino-2-tiokso-6-(3,4,5-trimetoksifenil)-1,2-dihidropirimidin-5-karbonitril (7d) imaju značajno antimikrobno djelovanje.

  • S. H. Bantawal, M. Manjathuru, K. S. Mari and K. M. Padiyath, Synthesis of some novel pyrazolo[3,4-d]pyrimidine derivatives as potential antimicrobial agents, Bioorg. Med. Chem. 14 (2006) 2040-2047; DOI: 10.1016/j.bmc. 2005.10.053.

  • C. Mugnaini, F. Manetti, J. Esté, I. Clotet-Codina, G. Maga, R. Cancio, M. Botta and F. Corelli, Synthesis and biological investigation of S-aryl-S-DABO derivatives as HIV-1 inhibitors, Bioorg. Med. Lett. 16 (2006) 3541-3544; DOI: 10.1016/j.bmc.2006.03.080.

  • A. B. Adnan, T. Y. Hesham, A. F. Sherif and M. B. Azza, Design and synthesis of some substituted 1H-pyrazolyl-thiazolo[4,5-d]pyrimidines as anti-inflammatory-antimicrobial agents, Eur. J. Med. Chem. 38 (2003) 27-36; DOI: 10.1016/S0223-5234(02)00009-0.

  • E. A. Abdel-Galil, M. M. Ashraf, F. M. Salwa, A. A. Nagla and G. H. Abu El-Fotooh, Anticancer activities of some newly synthesized pyridine, pyrane and pyrimidine derivatives, Bioorg. Med. Chem. 14 (2006) 5481-5488; DOI: 10.1016/J.bmc.2006.04.045.

  • M. T. Cocco, C. Congiu, V. Lilliu and V. Onnis, Synthesis and in vitro antitumoral activity of new hydrazinopyrimidine-5-carbonitrile derivatives, Bioorg. Med. Chem. 14 (2006) 366-372; DOI: 10.1016/j.bmc.2005.08.012.

  • N. Zhang, S. Ayral-Kaloustian, T. Nguyen, R. Hernandez and C. Beyer, 2-Cyanoaminopyrimidines as a class of antitumor agents that promote tubulin polymerization, Bioorg. Med. Chem. Lett. 17 (2007) 3003-3005; DOI: 10.1016/j.bmcl. 2007.03.070.

  • N. Sirisoma, S. Kasibhatla, B. Nguyen, A. Pervin, Y. Wang, G. Claassen, B. Tseng, J. Drewe and S. Xiong, Discovery of substituted 4-anillino-2-(2-pyridyl)pyrimidines as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. Part I: Structure-activity relathionships of the 4-anilino group, Bioorg. Med. Chem. 14 (2006) 7761-7773; DOI: 10.1016/j.bmc.2006.08.002.

  • P. Sharma, N. Rane and V. K. Gurram, Synthesis and QSAR studies of pyrimido[4,5-d]pyrimidine-2,5-dione derivatives as potential antimicrobial agents, Bioorg. Med. Chem. Lett. 14 (2004) 4185-4190; DOI: 10.1016/j.bmcl. 2004.06.014.

  • K. S. Jain, T. S. Chitre, P. B. Miniyar, M. K. Kathiravan, V. S. Bendre, V. S. Veer, S. R. Shahane and C. J. Shishoo, Biological and medicinal significance of pyrimidines, Curr. Sci. 90 (2006) 793-803.

  • O. A. Fathalla, S. M. Awad and M. S. Mohamed, Synthesis of new 2-thiouracil-5-sulphonamide derivatives with antibacterial and antifungal activity, Arch. Pharm. Res. 28 (2005) 1205-1212; DOI: 10.1007/bf02978199.

  • O. A. Fathalla, W. A. Zaghary, H. H. Radwan, S. A. Awad, and M. S. Mohamed, Synthesis of new 2-thiouracil-5-sulphonamide derivatives with expected biological activity, Arch. Pharm. Res. 25 (2002) 258-269; DOI: 10.1007 bf 0 2976623.

  • Y. Ding, J. Girardet, K. L. Smith, G. L. Prigaro, J. Z. Wu and, N. Yao, Parallel synthesis of 5-cyano-6-aryl-2-thiouracil derivatives as inhibitors for hepatitis C viral NS5B RNA-dependent RNA polymerase, Bioorg. Chem. 34 (2006) 26-38; DOI: 10.1016/j.bioorg.2005.10.001.

  • N. Agarwal, P. Srivastava, S. K. Raghuwanshi, D. N. Upadhyay, S. Sinha, P. K. Shukla and V. J. Ram, Chloropyrimidines as a new class of antimicrobial agents, Bioorg. Med. Chem. 10 (2002) 869-874; DOI: 10.1016/S0968-0896(01)00374-1.

  • A. W. Bauer, M. M. Kirby, J. C. Sherris and M. Turck, Antibiotic susceptibility testing by a standardized single disc method, Am. J. Clin. Pathol. 45 (1996) 493-496.

  • A. A. Aly, Synthesis and antimicrobial activity of some annelated quinazoline derivatives, J. Chin. Chem. Soc. 54 (2007) 437-446.

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

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