SINTEZA ȘI STUDIUL UNOR N'-(n-DIMETILFENIL)-N,N-DIMETILTIOUREI ȘI N(4)-n-DIMETILFENIL-TIOSEMICARBAZIDE

Tatiana ERHAN, Olga GARBUZ, Aurelian GULEA

Abstract


În lucrare este descrisă sinteza și activitatea antiproliferativă a 6 tiourei și a 6 tiosemicarbazide. Puritatea și identi­tatea compușilor obținuți a fost confirmată cu ajutorul spectroscopiei 1H și 13C RMN, IR, cromatografiei pe strat subțire CSS și al temperaturii de topire. Toate substanțele sintetizate au fost testate in vitro, pentru activitatea antiproliferativă pe liniile celulare umane de cancer, și anume: carcinom cervical (HeLa), carcinom pancreatic (BxPc-3), rhabdomiosarcomă (RD) și celule sănătoase de MDCK. S-a urmărit studiul relației structură-activitate.

THE SYNTHESIS AND STUDIES OF THE SOME N'-(n-DIMETHYLPHENYL)-N,N-DIMETHYLTHIOUREAS AND N (4)-n-DIMETHYLPHENYL-3-THIOSEMICARBAZIDES

The present paper describes the synthesis of 6 new thiosemicarbazides and 6 thioureas. The identity and purity of obtained organic compounds was proved by chromatography TSS, melting points, as well as by 13C and 1H NMR, IR spectra. The synthesized substances were tested, in vitro for the antiproliferative activity on cancer and normal cells of: HeLa (cervical cancer) cells, BxPc-3 (pancreatic cancer) cells, RD (rhabdomyosarcoma) cells and on normal MDCK cells. Structure-activity relationships were carried out.


Keywords


N (4)-n-dimethylphenyl-3-thiosemicarbazide, N'-(n-dimethylphenyl)-N,N-dimethylthiourea, antiproliferative activity, HeLa, BxPc-3, RD, MDCK.

Full Text:

PDF

References


METWALLY, M.A., BONDOCK, S., El-AZAP, H. and KANDEEL, E.M. Thiosemicarbazides: synthesis and reactions. In: Journal Sulfur Chemistry, 2011, vol.32, no.5, p.489-519.

SCHROEDER, D.C. Thioureas. In: Chemistry Review, 1955, vol.55, p.181-228.

ALY, A.A., AHMED, E.K., EL-MOKADEM, K.M., HEGAZY, M.E.-A.F. Update survey on aroyl substituted thioureas and their applications. In: Journal of Sulfur Chemistry, 2007, vol.28, p.73-93.

BURGESON, J.R., MOORE, A.L., BOUTILIER, J.K., CERRUTI, N.R., GHARAIBEH, D.N., LOVEJOY, C.E., AMBERG, S.M., HRUBY, D.E. et all. In: Bioorganic Medicinal Chemistry Letters, 2012, vol.22, p.4263-4272.

LIMBAN, C., MARUNTESCU, L., CHIFIRIUC, C. Synthesis, Spectroscopic Properties and Antipathogenic Activity of New Thiourea Derivatives. In: Molecules, 2011, vol.16, p.7593-7607.

KLAYMAN, D.L., BARTOSEVICH, J.F., GRIFFIN, T.S., MASON, C.J., SCOVILL, J.P. 2-Acetylpyridine thio-semicarbazones. 1. A new class of potential antimalarial agents. In: Journal of Medicinal Chemistry, 1979, vol.22, no.7, p.855-862.

HU, W.-X., ZHOU, W., XIA, C.-N., WEN, X. Synthesis and anticancer activity of thiosemicarbazones. In: Bioorganic and Medicinal Chemistry Letters, 2006, vol.16, no.8, p.2213-2218.

KHANDANI, M., SEDAGHAT, T., ERFANI, N., HAGHSHENAS, M.R., KHAVASI, H.R. Synthesis, spectroscopic characterization, structural studies and antibacterial and antitumor activities of diorganotin complexes with 3-metho¬xy¬salicylaldehyde thiosemicarbazone. In: Journal Molecular Structure, 2013, vol.1037, p.136-143.

AFRASIABI, Z., SINN, E., CHEN, J., MA, Y., RHEINGOLD, A.L., ZAKHAROV, L.N., RATH, N., PADHYE, S. Appended 1,2-naphthoquinones as anticancer agents 1: synthesis, structural, spectral and antitumor activities of ortho-naphthaquinone thiosemicarbazone and its transition metal complexes. In: Inorganic Chemica Acta, 2004, vol.357, no1, p.271-278.

LUKMANTARA, A.Y., KALINOWSKI, D.S., KUMAR, N., RICHARDSON, D.R. Synthesis and biological evaluation of substituted 2-benzoylpyridine thiosemicarbazones: novel structure–activity relationships underpinning their anti-proliferative and chelation efficacy. In: Bioorganic and Medicinal Chemistry Letters, 2013, vol.23, no4, p.967-974.

SHANMUGA, S., SUNDARA, RAJ, PUVIARASAN, K., VELMURUGAN, D., JAYANTHI, G. and FUN H.-K.

N-H, S hydrogen bonding in N-benzoyl-N’-methyl-N’-phenylthiourea and N-benzoyl-N’-(3,4-dimethylphenyl)thiourea. In: Acta Crystallographica C, 1999, vol.55, no.8, p.1318-1320.

ARSLAN, H., KULCU, N., and FLORKE, U. Normal coordinate analysis and crystal structure of N,N-dimethyl-N’-(2-chlorobenzoyl)thiourea. In: Spectrochimica Acta A, 2006, vol.64, no.4, p.1065-1071.

ARSLAN, H., DURAN, N., BOREKCI, G., KORAY OZER, C., AKBAY, C. Antimicrobial Activity of Some Thiourea Derivatives and Their Nickel and Copper Complexes. In: Molecules, 2009, vol.14, no.1, p.519-527.

ZHOU, W.Q., LI, B.L., ZHU, L.M., DING, J.G., YONG, Z., LU et al. Structural and spectral studies on N-(4-chloro) benzoyl-N'-(4-tolyl)thiourea. In: Journal Molecular Structure, 2004, vol.690, p.145-150.

MOUAYED A. HUSSEIN, MUHAMMAD ADNAN IQBAL, MUHAMMAD IHTISHAM UMAR et all. Synthesis, structural elucidation and cytotoxicity of new thiosemicarbazone derivatives. In: Arabian Journal of Chemistry, 2015.

ISOLDA C. MENDES, JULIANA P. MOREIRA, NIVALDO L. SPEZIALI, ANTONIO S. MANGRICH et all. N(4)-tolyl-2-benzoylpyridine Thiosemicarbazones and their Copper(II) Complexes with Significant Antifungal Activity. Crystal Structure of N(4)-para-tolyl-2-benzoylpyridine Thiosemicarbazone. In: Journal of the Brazilian Chemical Society, 2006, vol.17, no.8, p.1571-1577.

GULEA, A., POIRIER, D., ROY, J., STAVILA, V., BULIMESTRU, I., TAPCOV, V., BIRCA, M., POPOVSCHI, L. In vitro antileukemia, antibacterial and antifungal activities of some 3d metal complexes: Chemical synthesis and structure - activity relationships. In: Journal of Enzyme Inhibition and Medicinal Chemistry, 2008, vol.23, no.6, p.806-818.

ANOOPKUMAR-DUKIE, S., CAREY, JB., CONERE, T., O’SULLIVAN, E., VAN PELT, FN., ALLSHIRE, A. Resazurin assay of radiation response in cultured cells. In: The British Journal of Radiology, 2005, vol.78, no.934, p.945-947.

GULEA, A., GUDUMAC, V., GARBUZ, O., ANDRONACHE, L. In vitro antiproliferative activity and antioxidant capacity of new organometallic coordination compounds, results correlation analysis. In: Buletinul AŞM. Seria Ştiinţele vieţii, 2016, vol.3, nr.330, p.65.

GULEA, A., SARGUN, A., BARBA, A., JALBA, A., POIRIER, D., PETRENKO, P., CHUMAKOV, Yu. Synthesis and antileukaemia activity of N-(2,4-dimethylphenyl)hydrazine carbothioamide and its azomethine derivatives. In: Buletinul AŞM. Seria Ştiinţele vieţii, 2012, vol.3, nr.318, p.59-66.


Refbacks

  • There are currently no refbacks.