BACKGROUND: Cancer chemotherapy in humans based on metal complexes started at the clinical level in the late 1970s with the use of cisplatin, which forms intra-strand cross-links with DNA. METHODS: Two new platinum complexes of cis-geometry with the amino acids inosine (ino) and l-alanine (ala), Pt(ino)2Cl2 and cis-[Pt(NH3)2(ala)](NO3), respectively, were synthesized and pure samples were obtained by means of flash chromatography. These complexes were tested on benzo(a)pyrene-induced tumours in Wistar rats to detect their antitumour and toxic effects. RESULTS: There was a statistically significant prolongation of the mean survival time of the animals in the two groups tested (272 +/- 18 days and 246 +/- 26 days, respectively) compared to the control group (195 +/- 22 days) (P < 0.001). Toxic effects included a decrease in leucocyte cell count, mild haemolysis, mild haematuria, mild hepatotoxicity, elevated body temperature and hair loss. All of these effects were reversible after drug discontinuation. CONCLUSIONS: The two new platinum complexes described here appear to have an effective antitumour activity without severe toxicity when tested on Wistar rats.
BACKGROUND: Cancer chemotherapy in humans based on metal complexes started at the clinical level in the late 1970s with the use of cisplatin, which forms intra-strand cross-links with DNA. METHODS: Two new platinum complexes of cis-geometry with the amino acids inosine (ino) and l-alanine (ala), Pt(ino)2Cl2 and cis-[Pt(NH3)2(ala)](NO3), respectively, were synthesized and pure samples were obtained by means of flash chromatography. These complexes were tested on benzo(a)pyrene-induced tumours in Wistar rats to detect their antitumour and toxic effects. RESULTS: There was a statistically significant prolongation of the mean survival time of the animals in the two groups tested (272 +/- 18 days and 246 +/- 26 days, respectively) compared to the control group (195 +/- 22 days) (P < 0.001). Toxic effects included a decrease in leucocyte cell count, mild haemolysis, mild haematuria, mild hepatotoxicity, elevated body temperature and hair loss. All of these effects were reversible after drug discontinuation. CONCLUSIONS: The two new platinum complexes described here appear to have an effective antitumour activity without severe toxicity when tested on Wistar rats.
Authors: Nektaria Makrilia; Ekaterini Syrigou; Ioannis Kaklamanos; Leonidas Manolopoulos; Muhammad Wasif Saif Journal: Met Based Drugs Date: 2010-09-20