Ana Paula Soares Fontes

Synthesis and antitubercular activity of palladium and platinum complexes with fluoroquinolones

The fluoroquinolones are an important family of synthetic antimicrobial agents being clinically used over the past thirty years. In addition, some fluoroquinolones have been used in the development of anticancer drugs, and others have demonstrated anti-HIV activity. Furthermore, there has been some additional work investigating the effect of metal ions on biological activity. Aiming to obtain novel palladium(II) and platinum(II) complexes that exhibit biological activity, we have synthesized complexes using fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin, sparfloxacin, and gatifloxacin) as ligands. The compounds were characterized using IR and NMR spectroscopy, thermogravimetric and elemental analyses. The complexes show activity against Mycobacterium tuberculosis strain H(37)Rv. The minimal inhibitory concentration (MIC) of the complexes was determined.

Impact of the carbon chain length of novel platinum complexes derived from N-alkyl-propanediamines on their cytotoxic activity and cellular uptake.

This work describes the synthesis and characterization of four new ligands derived from 1,3-propanediamine in addition to the preparation and characterization of their respective platinum(II) complexes by reaction with K(2)PtCl(4). These ligands were obtained by the reaction of the corresponding alkyl mesylate with 1,3-propanediamine. We have prepared compounds having different carbon chains lengths in an attempt to correlate this factor, which influences the lipophilicity of the compounds, with cytotoxic activity. Octanol/water partition coefficients, the effect of the four complexes on the growth of two tumoral cell lines, and their cellular uptake were investigated. Increasing lipophilicity enhances the rate of cellular uptake and, consequently, the cytotoxic activity.

Three New Complexes of Platinum(II) with Doxycycline, Oxytetracycline and Chlortetracycline and their Antimicrobial Activity

Este artigo descreve a sintese e a caracterizacao de tres novos complexos de platina(II) com a oxitetraciclina, doxiciclina e clortetraciclina por analise elementar, espectroscopias IV e RMN de 195Pt. As interacoes da doxiciclina com ions PtII em funcao do pH foram estudadas por RMN de 1H. Todas as tetraciclinas investigadas formam complexos 1:1 com a PtII via oxigenio do grupo hidroxila e oxigenio do grupo amida do anel A. As concentracoes minimas inibitorias (MIC) dos ligantes e de seus complexos de PtII foram determinadas em duas cepas sensiveis (E. coli HB 101 and E. coli ATCC 25922) e em uma resistente (E. coli HB101/pBR322). O complexo de platina da doxiciclina e duas vezes mais potente do que o antibiotico livre na cepa resistente. Os coeficientes de particao dos complexos em octanol e agua foram determinados. O aumento da lipofilia causa um aumento da atividade antimicrobiana na cepa resistente.

4-aminoquinoline analogues and its platinum (II) complexes as antimalarial agents.

The high incidence of malaria and drug-resistant strains of Plasmodium have turned this disease into a problem of major health importance. One of the approaches used to control it is to search for new antimalarial agents, such as quinoline derivates. This class of compounds composes a broad group of antimalarial agents, which are largely employed, and inhibits the formation of β-haematin (malaria pigment), which is lethal to the parasite. More specifically, 4-aminoquinoline derivates represent potential sources of antimalarials, as the example of chloroquine, the most used antimalarial worldwide. In order to assess antimalarial activity, 12 4-aminoquinoline derived drugs were obtained and some of these derivatives were used to obtain platinum complexes platinum (II). These compounds were tested in vivo in a murine model and revealed remarkable inhibition of parasite multiplication values, whose majority ranged from 50 to 80%. In addition they were not cytotoxic. Thus, they may be object of further research for new antimalarial agents.

Synthesis of platinum complexes from N-benzyl ethylenediamine derivatives

O ligante N-benziletilenodiamina e derivados foram preparados em bons rendimentos utilizando-se metodologia diferente da descrita na literatura. Espectros de RMN de 1H e de 13C foram empregados para a caracterizacao destes compostos. Nove novos complexos de platina(II) com estes ligantes, analogos da cisplatina e da carboplatina, foram preparados e caracterizados. Testes preliminares in vitro em linhagens celulares de carcinoma bucal humano (celulas KB) indicam que estes complexos sao citotoxicos.

Trypanocidal activity of lipophilic diamines and amino alcohols

Trypanocidal activity of a number of lipophilic diamines and amino alcohols was evaluated in vitro against Trypanosoma cruzi blood stream forms. Several of the studied compounds showed inhibition of T. cruzi growth. The most active ones were compounds 3, 4 and 5 with a IC₅₀ of 31.2 μg/mL, activity similar to the reference drug crystal violet.

Platinum(II) and palladium(II) aryl-thiosemicarbazone complexes: synthesis, characterization, molecular modeling, cytotoxicity, and antimicrobial activity

Platinum(II) and palladium(II) complexes [ML2] have been isolated from reaction of K2PtCl4 or K2PdCl4 and ligands (L) derived from thiosemicarbazones. The complexes were characterized by elemental analysis, Raman, IR, and NMR spectroscopy. In addition, quantum mechanical calculations were used to predict their structures and spectroscopic properties. For the first time, theoretical calculations using 195Pt NMR data were used to support the suggested structures. The results indicate that the thionic sulfur and the azomethine nitrogen are bonded to the metal ion in a trans configuration. Antibacterial activities and cytotoxicities of the complexes to B16-F10 and CT26.WT cell lines were also investigated. Some of the complexes demonstrated superior cytotoxic activity compared to cisplatin. Graphical Abstract

Synthesis of Platinum Complexes from Sugar Derivatives

ABSTRACT Six new platinum(II) complexes containing a diamino sugar, analogs of cisplatin and carboplatin, have been prepared and characterized. The new ligands were obtained by reaction of D-galactose and D-ribose derivatives with ethylenediamine.

Compostos de platina em quimioterapia do câncer

The vast majority of clinically used antitumor drugs are either synthetic or natural product based organic compounds. In this review we describe different aspects, such as structure-activity relationships, mechanism of action, clinical uses and possible future prospects, of the platinum antitumor complexes, a distinct class of antitumor agents.

Novel platinum(II) complexes of long chain aliphatic diamine ligands with oxalato as the leaving group: comparative cytotoxic activity relative to chloride precursors

Platinum complexes play an important role in the development of anticancer drugs. Their cytotoxicity can be influenced by the nature of the leaving ligands, due to the hydrolysis reaction that occurs prior to the binding of the platinum complex to DNA. Also, non-leaving groups such as lipophilic diamines may affect cellular uptake. In this work, we describe the synthesis of platinum(II) complexes having oxalato and long chain aliphatic N-alkyl ethylenediamines as ligands. The products were characterized by elemental analyses, infrared spectroscopy and 1H, 13C and 195Pt NMR spectroscopy. Biological activity was assessed against tumor cell lines (A549, B16-F1, B16-F10, MDA-MB-231) and non-tumor cell lines (BHK-21 and CHO). The length of the carbon chain affects the cytotoxicity and the oxalato complexes were less cytotoxic than the respective chloride-containing analogues.