New tumor-inhibiting metal complexes

Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A

“…Some of them have reached an advanced milestone in the pre-clinical investigation (Keppler et al, 1990;Sava et al, 1998a) and one, namely imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate (NAMI-A) (Mestroni et al, 1998), is successfully completing a phase I clinical trial at the Netherlands Cancer Institute of Amsterdam (J Schellens, personal communication). The initial evidences on the mode of action of NAMI-A, although far from the clear elucidation, showed this compound free of direct cytotoxicity for tumour cells and of effects on primary tumour growth (Sava et al, 1998a;Bergamo et al, 1999;Zorzet et al, 2000).…”

β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding

“…Compound 5 was previously reported, [28] and all other compounds have been fully characterised by 1 H NMR Scheme 1 Synthetic pathway a), b) and c) for bis(-diketonate)titanium compounds 1-31 and Budotitane. [16] spectroscopy, 13 Figure 4 and the structures adopt a mix of geometries either cis-trans-cis or cis-cis-trans with half or one molecule in the asymmetric unit cell. The crystallographic data is presented in Table S1-S2 (see SI).…”

“…[20] SRB Chemosensitivity Studies In the first instance compounds were chosen to be tested using the SRB assay, these were selected according to previous cytotoxicity results we have obtained. [16] Compounds 5, 6, 9-14, 19-23, 25 and 26, and cisplatin were incubated with A2780 (human ovarian carcinoma), A2780cis (cisplatin-resistant human ovarian carcinoma), CaSki (human cervical carcinoma), HT-29 (human colorectal adenocarcinoma), LoVo (human colorectal adenocarcinoma), MCF-7 (human breast adenocarcinoma) and PC3 (human prostate cancer) cell lines, and results are presented in Table 1. The results show a general trend that the -diketonate titanium bromide compounds are more cytotoxic than their corresponding -diketonate titanium chloride compounds.…”

“…[16] Further mechanistic studies have been carried out to understand the solvolysis of these titanium compounds with DMSO and water, in particular compound 10 which contains a bromide ancillary ligand. It is thought that determining the mechanism of action of these drugs in the MTT assay should help to gain an understanding of the behavior of titanium drugs in the body.…”

“…[16][17][18] The in vivo results highlighted this compound as an attractive therapeutic drug due to its high activity against a range of transplantable tumors, with no known evidence of mutagenicity. However, the clinical trials were terminated at Phase I due to severe adverse side effects.…”