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Synthesis, characterization and determination of antimicobacterial and antitumoral activities of Ag(I), Au(I), Pd(II) e Pt(II) complexes with sweeteners and derivatives

Grant number: 05/02850-5
Support Opportunities:Regular Research Grants
Duration: February 01, 2006 - June 30, 2008
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Antonio Carlos Massabni
Grantee:Antonio Carlos Massabni
Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


Inorganic complexes have been used in Medicine for treatment of several diseases such as cancer, arthritis and bacterial infections. Palladium and platinum complexes are used in cancer chemotherapy. Cisplatin, cis-[PtCl2(NH3)2], discovered by Barnet Rosenberg in 1965, was the first complex used in cancer chemotherapy and it is the most widely used inorganic complex in Medicine. Its mechanism of action basically involves binding to DNA of tumor cells, inhibiting replication and transcription. Cisplatin is effective against ovarian, testicular, colon and cervical tumors. In testicular cancer treatment, it has a greater than 90% cure rate. Au(I) complexes, such as auranofin, are clinically used for rheumatoid arthritis treatment and Ag(I) complexes have antibacterial effects. Silver sulphadiazine is topically used to prevent bacterial infections in severe burns. However, these compounds have some disadvantages, as high manufacture costs, low solubility, increased drug resistance and side effects, specially neurological and renal disturbance (due to toxic phosphines as ligands). As an example, cisplatin, despite of the success of the clinical treatment, has its total effectiveness limited by side effects (neurological and renal disturbance) and acquired and intrinsic drug resistance. Resistance is a consequence of cellular repairing mechanisms by nucleotide excision repair (NER) reactions which remove DNA-cisplatin adducts and repair DNA, allowing normal cell replication and transcription. So, it is important the synthesis of new compounds active against a wide spectrum of tumors and which present less side-effects. A strategy found in more recent researches is the synthesis and design of structure of novel platinum complexes, in order to make possible new modes of DNA binding and, consequently, to inhibit repairing cellular mechanisms... (AU)

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