Platinum(II) compounds of tetracyclines as potential anticancer agents: cytotoxicity, uptake and interactions with DNA

Abstract

, respectivamente. Os complexos deslocam o brometo de etídeo dos sítios no ADN, o que indica um mecanismo intercalativo. Ambos os complexos diminuem a mobilidade eletroforética e a temperatura de fusão do ADN. Após a incubação das células com 1 e 2, o ADN foi extraído e os adutos formados foram quantificados. Na concentração em que os compostos são citotóxicos contra células cancerosas, eles não afetam a viabilidade de macrófagos. A velocidade de entrada do complexo da doxiciclina nas células é três vezes maior do que a do complexo da tetraciclina e isto parece ser determinante para a sua maior atividade.The antitumoral properties of Pt II compounds and the favorable characteristics of tetracyclines led us to study Pt II compounds of tetracycline (tc) and doxycycline (dox) as candidates for anticancer agents. [PtCl 2 (dox)], 1, is more potent than [PtCl 2 (tc)], 2, in inhibiting the growth of chronic myelogenous leukemia cells. Compounds 1 and 2 form a ternary complex with DNA with K values of 3.85×10 4 and 5.43×10 4 , respectively. The compounds displace ethidium bromide from DNA sites, which points to an intercalative mechanism. Both complexes decrease DNA eletrophoretic mobility and melting temperature. After incubation of cells with 1 and 2, the DNA was extracted and the adducts formed were quantified. At the concentration that the compounds are cytotoxic to cancer cells, they do not affect macrophages viability. The rate of uptake of the doxycycline complex in cells is three times higher than that of the tetracycline complex and this seems to be determinant for its higher activity.

Determination of Tetracycline in Pharmaceutical Preparation by Molecular and Atomic Absorption Spectrophotometry and High Performance Liquid Chromatography via Complex Formation with Au(III) and Hg(II) Ions in Solutions

“…The IR spectrum of the free TC. HCl showed two absorption bands at 3280–3480 cm −1 attributed to O-H stretching vibrations that undergo intermolecular hydrogen bonding [6, 15]. This band was shifted to higher frequencies at 3379–3439 cm −1 and to 3340–3440 cm −1 in the spectra of Au(III) and Hg(III) complexes, respectively, which rules out the coordination of the hydroxyl group with the two metal ions.…”

“…Beside the pharmacological importance of tetracycline (TC), this molecule possesses many potential metal-binding sites. Therefore a wide range of research work has been reported on chelation of TCs with various metal ions which have been utilized successfully in pharmaceutical analysis [1–15]. …”

“…Platinum(II) complexes of tetracycline and doxycycline were reported to bind to DNA and inhibit tumoral cell growth [15]. Although the Au(III) is as important as Pt(II) ions in this aspect, little attention has been paid to Au(III) complexes of TC.…”

Coordenação de metais a antibióticos como uma estratégia de combate à resistência bacteriana

“…Este aumento na afinidade dos complexos frente ao DNA sugere que o mecanismo do efeito citotóxico deve envolver interações com o DNA. 31 É interessante comentar que tetraciclinas possuem uma série de propriedades não antibióticas e há vários estudos sendo conduzidos no sentido de se usar tetraciclinas no tratamento de doenças não infecciosas, tais como artrite reumatoide e câncer. [32][33][34][35][36][37] Curiosamente, apesar de tetraciclinas serem bons agentes complexantes, não há na literatura relatos de complexos destes ligantes com alguns metais considerados importantes do ponto de vista farmacológico, como exemplo, ouro, bismuto e prata.…”

Investigation of the potential antitumor radioactive complex of platinum(II) with tetracycline

“…1, and to investigate their antimicrobial and antitumor effects [20,21]. Tetracycline is an antibiotic of large spectrum but its use has been limited due to the emergence of bacterial resistance.…”