Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2017-03-17T12:18:44Z
No. of bitstreams: 1
2016 - Emanoel Hottes.pdf: 4033048 bytes, checksum: fe0f804a0e5a67c894370834c0964ff8 (MD5) / Made available in DSpace on 2017-03-17T12:18:44Z (GMT). No. of bitstreams: 1
2016 - Emanoel Hottes.pdf: 4033048 bytes, checksum: fe0f804a0e5a67c894370834c0964ff8 (MD5)
Previous issue date: 2016-04-07 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / CuII complexes containing thiazole and thioimidazole derivatives have been synthesized and characterized. The ligands (E)-2-(2-benzylidenehydrazinyl)-4-phenylthiazole (L1), (E)-2-(2-(4-chlorobenzylidene)hydrazinyl)-4-phenylthiazole (L2), (E)-2-(2-(4-methoxybenzylidene)hydrazinyl)-4-phenylthiazole (L3), (E)-4-phenyl-2-(2-(pyridin-2-ylmethylene)hydrazinyl)thiazole (L4), (E)-5-phenyl-1-(pyridin-2-ylmethyleneamino)-1H-imidazole-2(3H)-thione (L5) and (E)-1-(2-hydroxybenzylideneamino)-5-phenyl-1H-imidazole-2(3H)-thione (L6), reported in the literature, have been obtained in collaboration with Laboratory LaDMol-QM from UFRRJ. For these ligands, it is been performed qualitative calculations and molecular modeling by the semi empiric method PM6 for geometry optimization and estimate the relative energies of the frontier orbitals and conformers. The crystalline structure of the ligand L2 was determined by X-ray diffraction analysis. The CuII complexes have been obtained from the reactions of the ligands with CuCl2 in different stoichiometries. The proposed structures of the complexes have been formulated based on elemental analysis of CHN, electronic paramagnetic resonance (EPR) and electronic (UV-Vis) and vibrational (FTIR) spectroscopy. The results of EPR point to the occurrence of more than one CuII nucleus in all reaction products. For complexes CuL1-CuL3 with potentially bidentate ligands it has been proposed coordination from sulfur or nitrogen from thiazole ring and nitrogen from azomethine, with possible octahedral and/or square planar geometries. For CuL4-CuL6 with potentially tridentate ligands it is been proposed coordination from sulfur as well as nitrogen atoms. For CuL6, there is also a possibility of coordination through the oxygen atom, with a CuII possibly pentacoordinate.. Studies with yeast have shown that amongst the compounds, L1 has had the best activity in the inhibition of the cell growth. It was possible to observe that all compounds decrease the cell survival during the period of incubation. The studies of lipid peroxidation have shown that the complexes were more toxic than the ligands and the complex CuL3 has shown better toxicity when compared to the other compounds and the control. / Complexos de CuII com ligantes derivados de tiazol e tioimidazol, foram sintetizados e caracterizados. Os ligantes (E)-2-(2-benzilidenohidrazinil)-4-feniltiazol (L1), (E)-2-(2-(4-clorobenzilideno)hidrazinil)-4-feniltiazol (L2), (E)-2-(2-(4-metoxibenzilideno)hidrazinil)-4-feniltiazol (L3), (E)-4-fenil-2-(2-(piridin-2-il-metileno)hidrazinil)tiazol (L4), (E)-5-fenil-1-((piridin-2-il-metileno)amino)-1H-imidazol-2(3H)-tiona (L5) e (E)-1-((2-hidroxibenzilideno)amino)-5-fenil-1H-imidazol-2(3H)-tione (L6), j? reportados na literatura, foram obtidos e caracterizados em parceria com o Laborat?rio LaDMol-QM da UFRRJ. Para estes ligantes foram realizados c?lculos qualitativos de modelagem molecular pelo m?todo semi-emp?rico PM6 para otimiza??o de geometria e estimativas de energias relativas de orbitais de fronteira e de conf?rmeros. A estrutura cristalina do ligante L2 foi determinada por difra??o de raios-X de monocristal. Os complexos de CuII foram obtidos a partir de rea??o dos ligantes com CuCl2 em diferentes estequiometrias. As propostas para os complexos foram formuladas com base nos dados de an?lise elementar de CHN, resson?ncia paramagn?tica eletr?nica (EPR) e espectroscopias eletr?nica (UV-vis) e vibracional (FTIR). Os resultados de EPR apontam para a ocorr?ncia de mais de um n?cleo de CuII em todos os produtos. Para os complexos CuL1-CuL3 com ligantes potencialmente bidentados (L1-L3) foi proposta complexa??o tanto pelo ?tomo de enxofre (anel tiazol) como tamb?m pelos ?tomos de nitrog?nio (azometino), com possibilidades de geometrias octa?dricas e tamb?m quadradas. J? os complexos CuL4-CuL6, com ligantes potencialmente tridentados (L4-L6), foi proposta complexa??o tanto pelo ?tomo de enxofre do anel tiazol como tamb?m pelos ?tomos de nitrog?nio do azometino e do anel pirid?nico. No caso de CuL6 ainda h? possibilidade de coordena??o atrav?s do ?tomo de oxig?nio, com CuII possivelmente pentacoordenado.. Testes realizados em leveduras mostraram que dentre os compostos, o L1 foi o que apresentou melhor desempenho na inibi??o do crescimento das c?lulas. No caso do teste de viabilidade foi poss?vel observar que todos os compostos diminuem a sobrevida celular no per?odo de incuba??o. Por meio da an?lise de peroxida??o lip?dica foi poss?vel verificar que os complexos foram mais t?xicos do que os ligantes e que o CuL3 foi o que apresentou maior toxidez quando comparado com os demais complexos e com o controle
| Identifer | oai:union.ndltd.org:IBICT/oai:localhost:jspui/1462 |
| Date | 07 April 2016 |
| Creators | Hottes, Emanoel |
| Contributors | Neves, Amanda Porto, Herbst, Marcelo Hawrylak, Carvalho, Nak?dia Maysa Freitas, Guedes, Guilherme Pereira |
| Publisher | Universidade Federal Rural do Rio de Janeiro, Programa de P?s-Gradua??o em Qu?mica, UFRRJ, Brasil, Instituto de Ci?ncias Exatas |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFRRJ, instname:Universidade Federal Rural do Rio de Janeiro, instacron:UFRRJ |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | Refer?ncias BIBLIOGR?FICAS [1] Shivarama. H. S. B.; Malini. V. K.; Sooryanarayana. B.; Sarojini. K. B.; Kumari. S. N. Synthesis of some new 2,4-disubstituted thiazoles as possible antibacterial and anti-inflammatory agents. Eur. J. Med. Chem. 2003, 38, 313-318. [2] Harnett. J. J.; Roubert. V.; Dolo. C.; Charnet. C.; Spinnewyn. B.; Cornet. S.; Rolland.; Marin. G. J.; Bigg. D.; Chabrier. E. P. Phenolic thiazoles as novel orally-active neuroprotective agents. Bioorg. Med. Chem. Lett. 2004, 14, 157-160. [3] Hassan. G. S.; Shahenda. M. E.; Fatmah. A. M.; Hussein. I. E. Substituted thiazoles VII. Synthesis and antitumor activity of certain 2-(substituted amino)-4-phenyl-1,3-thiazole analogs. Bioorg. Med. Chem. Lett. 2012, 22, 6318-6323. [4] Fatmah A.M.; Hassan. S. G.; Shahenda. M. E.; Hussein. I. E. Substituted thiazoles V. Synthesis and antitumor activity of novel thiazolo[2,3-b] quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues. Eur. J. Med. Chem. 2012, 47, 65-72. [5] Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Varoli, L.; Calonghi, N.; Cappadone, C.; Farruggia, G.; Zini, M.; Stefanelli, C.; Masotti, L.; Radin, N. S.; Shoemaker, R. H. New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues. J. Med. Chem. 2008, 51, 809?816. [6] El-Messery. M. S.; Hassan. S. G.; Al-Omary. A. M. F.; El-Subbagh. I. H. Substituted thiazoles VI. Synthesis and antitumor activity of new 2-acetamido- and 2 or 3-propanamido-thiazole analogs. Eur. J. Med. Chem. 2012, 54, 615-625. [7] Andreani. A.; Granaiola. M.; Leoni. A.; Locatelli. A.; Morigi. R.; Rambaldi. M. Synthesis and antitubercular activity of imidazo[2,1-b]thiazoles. Eur. J. Med. Chem. 2001, 36, 743-746. 70 [8] Branowska. D.; Farahat. A.; Kumar. A.; Wenzler. T.; Brun.R.; Liu. Y.; W. David Wilson. W. D.; Boykin. W. D. Synthesis and antiprotozoal activity of 2,5 bis[amidinoaryl]thiazoles. Bioorg. Med. Chem. 2010, 18, 3551-3558. [9] Cardoso. O. V. M.; Siqueira. P. R. L.; Silva. B. E.; Costa. B. L.; Hernandes. Z. M.; Rabello. M. M.; Ferreira. S. R.; Cruz. F. L.; Moreira. M. R. D.; Pereira. A. R. V.; Castro. B. A. C. M.; Bernhardt. V. P.; Leite. L. C. A. 2-Pyridyl thiazoles as novel anti-Trypanosoma cruzi agents: Structural design, synthesis and pharmacological evaluation. Eur. J. Med. Chem. 2014, 86, 48-59. [10] Siddiqui. N.; Arshad. F. M.; Ahsan. W.; Alam. S. M. Thiazoles: A Valuable Insight into the Recent Advances and Biological Activities. International Journal of Pharmaceutical Sciences and Drug Research. 2009, 1, 136-143. [11] Souza. M. M?todos de obten??o e aplica??es sint?ticas de tiaz?is, uma importante classe de compostos heteroc?clicos. Quim. Nova. 2005, 28, 77-84. [12] Shiradkar. R. M.; Akula. C. K.; Dasari. V.; Baru. V.; Chiningiri. B.; Santosh Gandhi. S.; Ranjit Kaur. R. Clubbed thiazoles by MAOS: A novel approach to cyclin-dependent kinase 5/p25 inhibitors as a potential treatment for Alzheimer?s disease. Bioorg. Med. Chem. 2007, 15, 2601-2610. [13] Moreira. M. R. D.; Costa. M. P. S.; Hernandes. Z. M. Structural Investigation of Anti-Trypanosomacruzi 2-Iminothiazolidin-4-ones Allows 142 the Identification of Agents with Efficacy in Infected Mice. J. Med. Chem. 2012, 55, 10918-10936. [14] Filho. G. B. O. Planejamento estrutural, s?ntese e avalia??o das propriedades tripanocidas de 4-tiazolinonas e seus an?logos estruturais do tipo 1,3-tiaz?is. Disserta??o de mestrado. Recife-PE, 2013. [15] Gomes. P. A. T. M. S?ntese e Avalia??o da Atividade Anti-Trypanosoma cruzi de In?ditas Tiazolil-Hidrazonas. Disserta??o de mestrado Recife-PE, 2013. 71 [16] Peng-Cheng. Lv.; Wang. R-K.; Yang. Y.; Mao. J-W.; Jin Chen, Jing Xiong. J.; Zhu. L-H. Design, synthesis and biological evaluation of novel thiazole derivatives as potent FabH inhibitors. Bioorg. Med. Chem. Lett. 2009, 19, 6750-6754. [17] Alam. S. M.; Liu. L.; Lee. E-Y.; Lee. U-D. Synthesis, Antibacterial Activity and Quantum-Chemical Studies of Novel 2-Arylidenehydrazinyl-4-arylthiazole Analogues. Chem. Pharm. Bull. 2011, 59, 568-573. [18] Aliabadi. A.; Shamsa. F.; Ostad. N. S.; Emami. S.; Shafiee. A.; Davoodi. J.; Foroumad. A. Synthesis and biological evaluation of 2-phenylthiazole-4-carboxamide derivatives as anticancer agents. Eur. J. Med. Chem . 2010, 45, 5384-5389. [19] Fallah-Tafti. A.; Alireza Foroumadi. A.; Tiwari. R.; Shirazi. N. A.; Hangauer. G. D.; Bu. Y.; Akbarzadeh. T.; Parang. K.; Shafiee. A. Thiazolyl N-benzyl-substituted acetamide derivatives: Synthesis, Src kinase inhibitory and anticancer activities. Eur. J. Med. Chem. 2011, 46, 4853-4858. [20] Lefranc. F.; Xu. Z.; Burth. P.; Mathieu. V.; Revelant . G.; Faria. C. V. M.; Noyon. C.; Garcia. G. D.; Dufour. D.; Bruy?re. C.; Albuquerque. G. F. C.; Antwerpen. V. P.; Rogister. B.; Hesse. S.; Kirsch. G.; Kiss. R. 4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) inhibits Na+/K+-ATPase and Ras oncogene activity in cancer cells. Eur. J. Med. Chem. 2013, 63, 213-223. [21] Ignat. A.; Lovasz. T.; Mihai Vasilescu. M.; Fischer-Fodor. E.; Tatomir. B. C.; Cristea. C.; Silaghi-Dumitrescu. L.; Zaharia. V. Heterocycles 27. Microwave Assisted Synthesis and Antitumour Activity of Novel Phenothiazinyl-Thiazolyl-Hydrazine Derivatives. Arch. Pharm. Chem. Life Sci. 2012, 345, 574-583 [22] Kolodina. A. A.; Ganonenko. I. N.; Lesin. V. A. Synthesis of 3,4-dihydro-2h-imidazo-[2,1-b][1,3,4]thiadiazines. Chem. Heterocycl. Compd. 2007, 43, 1202-1209. [23] Gaponenko. I. N.; A. A. Kolodina. A. A.; Lesin. V. A.; Kurbatova. V. S. Intramolecular cyclization of S-alkyl derivatives o aminomercaptoimidazoles and ? 72 benzimidazoles as a method for the annulation of the thiadiazine ring. Russ. Chem. Bull. 2012, 64, 1154-1160. [24] Cotton. F. A, Wilkinson. G. Advanced Inorganic Chemistry: a comprehensive text. 5th ed. New York: John Wiley & Sons, 1988. [25] Jones, J. C. A Qu?mica dos elementos dos Blocos d e f. Bookman. p 107 -127, 2002. [26] Huheey, E. J. Inorganic Chemistry: Principles of Structure and Reactivity. 2 th ed. Harper International Edition (1978), [27] Zahid H. Chohan. H. Z.; Kausar. S. Synthesis, characterization and biological properties of tridentate nno, nns and nnn donor thiazole-derived furanyl, thiophenyl and pyrrolyl schiff bases and their Co(ll), Cu(ll), Ni(ll) and Zn(ll) metal chelates. Metal-Based Drugs. 2000, 7, 17-22. [28] Zahid, H. C. Ni(II), Cu(II) and Zn(II) Metal chelates with some thiazole derived schiff-bases?. Their synthesis, characterization and bactericidal properties. Metal-Based Drugs. 1999, 6, 75-80. [29] Chaviara. Th. A.; Cox. J. P.; Repana. H. K.; R.M. Papi. M. R.; Papazisis. T. K.; Zambouli . D Kortsaris. H. A.; Kyriakidis. A. D.; Bolos. A. C. Copper(II) Schiff base coordination compounds of dien with heterocyclic aldehydes and 2-amino-5-methyl-thiazole: synthesis, characterization, antiproliferative and antibacterial studies. Crystal structure of Cudien OOCl2. J. Inorg. Biochem. 2004, 98, 1271-1283. [30] Alez-Alvarez. G. M.; Alzuet. G.; Borr. J.; Agudo. C. L.; Garcia-Granda. S.; Bernardo. M. M. J. Strong protective action of Copper(II) N-substituted sulfonamide complexes against reactive oxygen species. J. Inorg. Biochem. 2004 ,98,189-198. [31] Bolos, C. A. Synthesis, characterization, toxicity, cytogenetic and in vivo antitumor studies of 1,1-dithiolate Cu(II) complexes with di-, tri-, tetra- amines and 1,3-thiazoles. Structure?activity correlation. Bioorg. Med. Chem. 2009, 17, 3142-3151. 73 [32] Grozav. A.; Balacescu. O.; Balacescu. L.; Cheminel. T.; Berindan-Neagoe. I.; Therrien. B. Synthesis, anticancer activity an Genome profiling of thiazolo arene ruthenium complexes. J. Met. Chem. 2015, 58, 8475-8490. [33] Frija. T. M. L.; Pombeiro. L. J. A.; Kopylovich. N. M. Coordination chemistry of thiazoles, isotiazoles and thiodiazoles. Coord. Chem. Rev. 2016, 308, 32-55. [34] Bharti. K. S.; Singh. K. S. Design, synthesis and biological evaluation of some novel benzylidene-2-(4-phenylthiazol-2-yl) hydrazines as potential anti-inflammatory agents. Med. Chem. Res. 2014, 23, 1004?1015. [35] Dash. D. C.; Mahapatra. A.; Jena. P.; Naik. S. K.; Mishra. U. K. Synthesis and characterization of some transition metal complexes with 4-(phenyl/p-bromophenyl)thiazolyl hydrazine of furfural. J. Indian Chem. Soc. 2007, 84, 1092-1095. [36] SHIH. H-M.; SU. S-Y.; WU. L-C. Syntheses of Aromatic Substituted Hydrazino-thiazole Derivatives to Clarify Structural Characterization and Antioxidant Activity between 3-Arylsydnonyl and Aryl Substituted Hydrazino-thiazoles. Chem. Pharm. Bull. 2007, 55, 1126-1135. [37] Tuzimoto. P. A. S?ntese, Caracteriza??o e Estudo das Propriedades Mesom?rficas e Fotof?sicas de Compostos Contendo as Unidades tiadiazolfenantrolina, antraquinona, tiadiazol e tiazol. Disserta??o de mestrado. Florian?polis 2014. [38] Oliveira. M. S.; Silva. P. B. J.; Hernandes. Z. M.; Lima. A. C. M.; Galdino. L. S.; Pitta. R. I. Estrutura, reatividade e propriedades biol?gicas de hidanto?nas. Quim. Nova. 2008, 31, 614-622. [39] Vugman, V. N; Herbst, H. M. Fundamentos e Aplica??es da Resson?ncia Magn?tica Nuclear: Introdu??o ? Resson?ncia Paramagn?tica Eletr?nica de onda cont?nua. Aplica??es ao estudo de complexos de metais de transi??o. AUREMN. N. 3, 2007. [40] Mariani, D. Citotoxicidade e fun??o do sistema de defesa antioxidante durante a exposi??o a cisplatina no modelo Saccharomyces cerevisiae. Disserta??o de mestrado. Rio de Janeiro 2008 |
Page generated in 0.0032 seconds