CONCLUSÕES

Nesse trabalho, foram sintetizados a 1,10-fenantrolina-5,6-diona, com rendimento de 75%, os ligantes dppz e dpq, com rendimentos de 61% e de 68%, respectivamente, e os complexos metálicos [Ag(PPh3)2]NO3 (1), [Ag(PPh3)2(dppz)]NO3 (3), [Ag(dppz)2]NO3 (5),

[Ag(dpq)2]NO3 (6), [Ag(PPh3)(dpq)NO3] (7), [Ag(PTA)2(dpq)]NO3 (8),

[Ag(PTA)2(dppz)]NO3 (9), [Zn(dppz)2](NO3)2 (10), [Zn(dppz)2]Cl2 (11) e [Zn(dpq)2]NO3 (12)

com rendimentos que variaram de 42-88%.

Por meio da utilização de todas as técnicas espectroscópicas e analíticas disponíveis, tais como espectroscopia na região do UV-Vis., infravermelho, massas, RMN de 1H e 31P, análise elementar de CHN e difração de raios X (para o complexo [Ag(PPh3)2(dppz)]NO3),

tais compostos puderam ser caracterizados e tiveram sua estrutura elucidada.

Os testes de interação dos complexos de Ag(I) com o DNA, feitos utilizando-se as técnicas de ensaios de titulação espectrofotométrica e viscosidade indicaram que os mesmos interagem com o DNA via intercalação.

Os compostos [Ag(PPh3)2(dppz)]NO3 (3), [Ag(dppz)2]NO3 (5) e [Ag(dpq)2]NO3 (6)

foram enviados para teste biológico em parceria com o Dr. Celso Santana, da Divisão de Metrologia Aplicada às Ciências da Vida (DIMAV) – INMETRO e os resultados preliminares apontaram pouca variação na viabilidade das linhagens celulares estudadas em comparação ao controle. Os demais compostos serão enviados posteriormente.

Não houve sucesso na tentativa de melhorar as condições experimentais para aumentar o rendimento da reação de obtenção do complexo metálico [Zn(PPh3)2Cl2] (2) e,

consequentemente, não foi possível aumentar o rendimento da reação do mesmo com o ligante dppz.

7.1 PERSPECTIVAS FUTURAS

Pretende-se realizar mais experimentos de interação com o DNA dos compostos obtidos nesse trabalho por meio de ensaios de mudança eletroforética e absorção atômica.

Pretende-se também, utilizar os resultados obtidos nesse trabalho na produção de artigos científicos com posterior publicação em revistas científicas especializadas e em congressos da área.

85

REFERÊNCIAS

ADHIKARI, A. et al. Zinc complex of tryptophan appended 1,4,7,10-tetraazacyclododecane as potential anticancer agent: Synthesis and evaluation. Bioorganic & Medicinal Chemistry, v. 25, p. 3483–3490, 2017.

ALEXANDRE, T. et al. Ergosterol isolated from the basidiomycete Pleurotus

salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 23, p. 1-10, 2017.

ALMEIDA, M. V. et al. Synthesis and antitubercular activity of lipophilic moxifloxacin and gatifloxacin derivatives. Bioorganic & Medicinal Chemistry Letters, v. 17, p. 5661–5664, 2007.

ANJOS (Pra quem tem fé). Marcelo Falcão, Tom Saboia. Rio de Janeiro: Warner Records, 2013. 1 CD (51 min).

BARAN, E. J. Metalofármacos: Una nueva perspectiva para la farmacología y la medicina. Anales de la Academia Nacional de Ciencias Exactas, Fisicas y Naturales, v. 66, p. 5–21, 2014.

BARBOSA, M. I. F. et al. Antiparasitic activities of novel ruthenium/lapachol complexes. J. Inorg. Biochem., v. 136, p. 33-39, 2014.

BARRA, C. V.; NETO, A.V.G. Antitumour Complexes and DNA Interactions and their Tools of Analysis: na approach to metalointercalators. Revista virtual de química, v. 7, p. 1998- 2016, 2015.

BARRON, P. F.; DYASON, J. C.; HEALY, P. C. Lewis Base Adducts of Group 11 t Metal Compounds. Part 24.$ Co-ordination of Triphenylphosphine with Silver Nitrate. A Solid-state Cross-polarization Magic Angle Spinning 31 P Nuclear Magnetic Resonance, Crystal

Structure, and Infrared Spectroscopic Study. J. Chem. Soc. Dalton Trans., p. 1965-1970, 1986.

Bula da Cisplatina. Acesso em 20 de junho de 2019, disponível em MedicinaNET: http://www.medicinanet.com.br/bula/1446/cisplatina.htm

BURRI, C. B. Human African trypanosomiasis In Manson’s tropical diseases. W.B. Saunders/Elsevier, p. 1303-1323, 2003.

CALDERAZZO F, M. F. Co-ordination properties of 1,10-phenanthroline-5,6-dione towards group 4 and 5 metals in low and high oxidation states . The Royal Society of Chemistry, p. 4389-4396, 1999.

CHAUHAN, A. K. S. et al. Synthesis and characterization of triarylphosphine complexes of zinc(II) halides. Appl. Organometal. Chem, v. 17, 2003.

COLINA-VEGAS, L. et al. Ru(II)/clotrimazole/diphenylphosphine/bipyridine complexes: Interaction with DNA, BSA and biological potential against tumor cell lines and

Mycobacterium tuberculosis.J. Inorg. Biochem., v. 162, p. 135-145, 2016.

CORREA, R.S. et al. Ru(II)-based complexes with N-(acyl)-N′,N′-(disubstituted)thiourea ligands: Synthesis, characterization, BSA- and DNA-binding studies of new cytotoxic agents against lung and prostate tumour cells. J. Inorg. Biochem., v. 150, p. 63-71, 2015.

CUCUNUBÁ, Z. M. et al. Complementary paths to Chagas disease elimination: the impact of combining vector control with etiological treatment. Clin Infect Dis. 66(S 4):S293–S300, 2018.

DICKESON, J.E.; SUMMERS, L. A. Derivatives of 1,10-Phenanthroline-5,6-quinone. Aust J Chem, v. 23(5), p. 1023-1027, 1970.

DO NASCIMENTO, F. B. et al. Synthesis, characterization, X-ray structure and in vitro antimycobacterial and antitumoral activities of Ru(II) phosphine/diimine complexes

containing the "SpymMe2" ligand, SpymMe2=4,6-dimethyl-2-mercaptopyrimidine.J. Inorg. Biochem., v. 102(9), p. 1783-1789, 2008.

DOS REIS, D. B. et al. Synthesis and biological evaluation against Mycobacterium

tuberculosis and Leishmania amazonensis of a series of diaminated terpenoids. Biomedicine & Pharmacotherapy. v. 84, p. 1739–1747, 2016.

EJAZI, S. A.; ALI, N. Developments in diagnosis and treatment of visceral leishmaniasis during the last decade and future prospects Expert Rev. Anti-Infect. Ther, v. 11(1), p. 79+, 2013.

FARRELL, N. P. Multi-platinum anti-cancer agents. Substitutioninert compounds for tumor selectivity and new targets. Chem. Soc. Rev., p. 8773−8785, 2015.

FONTES, A. P. S.; ALMEIDA S. G. Compostos de platina em quimioterapia do câncer. Química Nova, v. 20, p. 398, 1997.

FONTES, A. P.; CÉSAR, E.T.; BERALDO, H. A. Química inorgânica na terapia do câncer. Química Nova na Escola, v. 6, p. 2–7, 2005.

FRANCISCO, A. I.; VARGAS, M. D. Ferroquina: O Antimalárico do Futuro. Revista virtual de química, v. 2, p. 118-129, 2010.

FRÉZARD, F.; DEMICHELI, C.; RIBEIRO, R. R. Pentavalent Antimonials: New Perspectives for Old Drugs. Molecules v. 14, p. 2317- 2336, 2009.

GRAY, A. et al. Reactivation of Chagas disease among heart transplant recipients in the United States, 2012–2016. Transpl Infect Dis, 2018.

HALDAR, A. K.; SEN, P.; ROY, S. Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions. Molecular Biology International 2011, v. 1, 2011.

87

HAQ, I. et al. Interaction of Δ- and Λ-[Ru(phen)2dppz]2+ with DNA: A Calorimetric and

Equilibrium Binding Study. J. Am. Chem. Soc. v. 117, p. 4788-4796, 1995.

Hay, P. J.; Wadt, W. R. Ab initio effective core potentials for molecular calculations. Potentials for K to Au including the outermost core orbitals. J. Chem. Phys., v. 82, p. 299−310, 1985.

KATO, K. C. et al. Hepatotoxicity of Pentavalent Antimonial Drug: Possible Role of Residual Sb(III) and Protective Effect of Ascorbic Acid. Antimicrobial Agents and Chemotherapy, v. 58, p.481, 2014.

LIANG, X. et al. Recent advances in the medical use of silver complex. Eur. J. Med. Chem. p. 62-80, 2018.

MARMUR, J. A procedure for the isolation of deoxyribonucleic acid from micro-organisms. J Mol. Biol. v.3, p. 208-218, 1961.

NAVARRO, M. et al. Metal-based drugs for malaria, trypanosomiasis and leishmaniasis: recent achievements and perspectives. Drug Discovery Today, v. 15, p. 1070–1078, 2010. NAVARRO, M. et al. Synthesis, characterization, DNA binding study and biological activity against Leishmania mexicana of [Cu(dppz)2]BF4. Journal of Inorganic Biochemistry,

p. 364-369, 2003a.

NAVARRO, M. et al. Synthesis and characterization of [Au(dppz)2]Cl3. DNA interaction

studies and biological activity against Leishmania (L) mexicana. Journal of Inorganic Biochemistry, p.111-116, 2007.

NAVARRO, M.; CISNEROS-FAJARDO, E.; MARCHAN, E. Synthesis, Characterization and Biological Activity on Leishmania mexicana. Arznelm Forsch/Drug Res, p. 600-604, 2006.

NAVARRO, M. et al. Design of cooper DNA intercalators with leishmanicidal activity. J Biol Inog Chem , p. 401-408, 2003.

NAVARRO, M. et al. Synthesis and anticancer activity of gold(I)-chloroquine complexes. J. Mex. Chem. Soc., v. 57, p. 220-229, 2013.

Organização Mundial da Saúde (OMS). Acesso em 30 de junho de 2019, disponível em http://www.who.int/cancer/en/ ; https://www.who.int/leishmaniasis/disease/en/;

https://www.who.int/chagas/disease/en/

PAVAN, F. R. et al. Ruthenium (II) phosphine/picolinate complexes as antimycobacterial agents. Eur. J. Med. Chem., p. 598-601, 2010.

PEARSON, R. G. Hard and soft acids and bases, HSAB, part 1: fundamental principles. Journal of Chemical Education, v. 45, p. 581, 1968.

PIZARRO, A. M.; SADLER, P. J. Unusual DNA binding modes for metal anticancer complexes. Biochimie, v. 91, p. 1198, 2009.

RAJENDIRAN, V. et al. Mixed-Ligand Copper(II)-phenolate Complexes: Effect of Coligand on Enhanced DNA and Protein Binding, DNA Cleavage, and Anticancer Activity. Inorg. Chem, p. 8208−8221, 2007.

REDDY, A. et al. Glycosylated metal chelators as anti-parasitic agents with tunable selectivity. Dalton Transactions, v. 46, p. 5297–5307, 2017.

ROY, P. Biological targeting and drug delivery in control of Leishmaniasis. Journal of Cell and Animal Biology, p. 73-87, 2012.

SATYANARAYANA, S; DRABOWIAK, J.C.; CHAIRES, J. B. Neither Δ-nor Λ

tris(phenanthroline)ruthenium(II) binds to DNA by classical intercalation, Biochemistry, v. 31, p. 9319-9324, 1992.

SCH FER, S.; SHELDRICK, . S. Coligand tuning of the DNA binding properties of half- sandwich organometallic intercalators: Influence of polypyridyl (pp) and monodentate ligands (L=Cl,(NH2)2CS,(NMe2)2CS) on the intercalation of (η5-pentamethylcyclopentadienyl)- iridium(III)- dipyridoquinoxaline and dipyridophenazine complexes. J. Organomet. Chem. v. 692, p.1300−1309, 2007.

SINGH, M. K. et al. Copper salisylaldoxime (CuSAL) imparts protective efficacy against visceral leishmaniasis by targeting Leishmania donovani topoisomerase IB. Experimental Parasitology, v. 175, p. 8–20, 2017.

SMOLENSKI, P. et al. New water-soluble polypyridine silver(I) derivatives of 1,3,5-triaza-7- phosphaadamantane (PTA) with significant antimicrobial and antiproliferative activities. Dalton Trans., v.42(18), p. 6572-6582, 2013.

STUART K. et al. Kinetoplastids: related protozoan pathogens, different diseases. J Clin Invest, p. 1301-1310, 2008.

TAPANELLI, S. et al. Novel metalloantimalarials: Transmission blocking effects of water soluble Cu(I), Ag(I) and Au(I) phosphane complexes on the murine malaria parasite Plasmodium berghei. Journal of Inorganic Biochemistry, v. 166, p. 1–4, 2017.

TUREL, I.; KLJUN, J. Interactions of metal ions with DNA, its constituents and derivatives, which may be relevant for anticancer research. Current Topics in Medicinal Chemistry, v. 11, p. 2661, 2011.

VILLARREAL, W. et al. Copper(I)−Phosphine Polypyridyl

Complexes:Synthesis,Characterization, DNA/HSA Binding Study, and Antiproliferative Activity. Inorganic Chemistry, p. 3781-3793, 2017.