Oxovanadium(V) complexes with bioactive hydrazones ligands: synthesis, structural characterization and study of the potencial trypanocidal activity

Author(s)

Murilo César Carroccia

• Document type: Master's Dissertation
• Press: São Carlos.
• Institution: Universidade de São Paulo (USP). Instituto de Química de São Carlos (IQSC/BT)
• Defense date: 2014-04-11

Examining board members

Victor Marcelo Deflon; Antonio Eduardo Mauro

• Advisor: Victor Marcelo Deflon

Abstract

Chagas disease, also called American trypanosomiasis is the third most present parasitic disease in the world. The existing therapies for this trypanosomiasis are unsatisfactory and a little attention has been given to the development of new drugs. The drugs currently used exhibit good activity only in the early phase of the disease and generate severe side effects in patients. <br /> Hydrazones represent a class of iminic compounds with good structural variability and important biological activity at various levels, and interesting results of trypanocidal activity are observed for hydrazones coordinated to ruthenium. On the other hand, complexes with oxovanadium coordinated to quinoxaline derivatives have better activities than the free ligands and complexes with other metals coordinated to that quinoxalines. <br /> This study aimed to unite the biological properties of hydrazones and vanadium to obtain complexes with good trypanocidal activity. Two hydrazones ligands derived from 2- tiofenofenohidrazida were synthesized, and through that ligands, ten new complexes of oxovanadium (V) were developed. The products were characterized by melting point, elemental analysis, infrared and UV - Vis. spectroscopies, nuclear magnetic resonance (1H NMR) and single crystals x-ray diffraction. Three classes of complexes were obtained. Two of them are formed by complexes with mixed ligands, one at [VO(L)(OR) ] form, with R = methyl , ethyl , n- propyl and L = hydrazone , and the other one with the [VO(L)(mal)] empirical form, with L = hydrazone and mal = pyrone maltol. Another class consists of binuclear oxovanadium complexes obtained at [(VOL)2(&mu;-O)] form, with L = hydrazone and the vanadium centers connected by a &mu;-oxo bridge. The structures obtained for the mixed complexes with the alkoxides and dimers have quadratic distorted pyramidal geometry, while the mixed maltol complexes have distorted octahedral geometry. <br /> In vitro assays against T. cruzi strains showed interesting results (SI equal to or greater than 10) to continue the exploration of the types of complexes formed and new biological tests must be conducted to verify the mechanism of action and in vivo activity of these compounds, in order to obtain a new vanadium-based antichagasic drug in the future. (AU)

• FAPESP's process: 11/16160-1 - Complexes of vanadium (+ IV and + v) and rhenium (+V) with bioactive ligands: synthesis, characterization and biological studies aiming obtaining potential anti-Mycobacterium tuberculosis and antiparasitic agents
• Grantee: Murilo César Carroccia
• Support Opportunities: Scholarships in Brazil - Master