A series of di-n-butyltin(IV) compounds of the type di-n-butyltin(IV)(X-A-B-Y) with the (X-A-B-Y) being related to salicylic acid was tested in vitro for cytotoxic activity against tumour cells of the human A 204, MCF-7, T24, WiDr and IgR-37 cell lines using the PIT method. In each cell line the di-n-butyltin(IV) compounds displayed similar activity. As compared to cisplatin, the compounds were 4- to 10-fold more effective against A 204, MCF-7 and T24 tumour cells and slightly more effective against WiDr cells. The effectiveness against IgR-37 cells was similar for cisplatin and di-n-butyltin (IV) compounds.

Cell Survival↗

PubMedDate not supplied

Electrochemistry of potential bioreductive alkylating quinones: its use in the development of new aziridinylquinones.

The concept of bioreductive alkylation as a mechanism of action of quinone-containing anticancer agents was investigated, using electrochemical techniques. According to this concept, an electrochemical step (reduction of the quinone ring) is followed by one or more chemical steps, leading to formation of the actual alkylating species. The proper use of electrochemical analysis of potential bioreductive alkylating quinones in the design of new analogs is limited. Up to now, the only electrochemical parameter frequently used in structure-activity relationship studies, is the half-wave potential of the quinone reduction. However, reliable information can only be obtained from the found value of this parameter when the reduction mechanism has been elucidated. Furthermore, it only gives information about the first step of the model. More detailed electrochemical analysis of potential bioreductive alkylating quinones, in combination with a biological evaluation, is required to gain more insight in their mechanism of action and to yield quantitative information about substituent effects on both the electrochemical and the chemical step(s) of the model. Results of such studies of a series of aziridinylquinones indicate, that the biological activity in vitro is correlated with the ease of protonation of the aziridines after quinone reduction, which is in accordance with the concept of bioreductive activation. No correlation with the ease of protonation of the aziridines prior to quinone reduction or with the quinone reduction step itself can be found.

Alkylating Agents↗

PubMedDate not supplied

In vitro antiproliferative activity of docetaxel (Taxotere), paclitaxel (Taxol) and cisplatin against human tumour and normal bone marrow cells.

The in vitro antiproliferative effect of docetaxel (Taxotere), paclitaxel (Taxol) and cisplatin was assessed in a range of human tumour types, including 25 tumour cell lines and 35 primary cultures. Additionally, 12 human normal bone marrow samples were analyzed. Seven laboratories, all members of the EORTC Preclinical Therapeutic Models Group (PTMG), have performed these tests, using their own individual assay procedures. In all comparisons docetaxel and paclitaxel were much more potent than cisplatin with IC50 values of the taxoids being in the nanomolar range. Docetaxel generally was two- to four-fold more cytotoxic than paclitaxel. The sensitivity profile of the cell lines, which was based on the IC50 values, indicated a certain degree of cross-sensitivity between paclitaxel and docetaxel (linear regression analysis; r = 0.73, p < 0.001). On the other hand, the sensitivity profile of cisplatin was different from the ones seen for docetaxel and paclitaxel, indicating that no cross-sensitivity exists between cisplatin and both taxoids.

Antineoplastic Agents, Phytogenic↗