The hypothesis was tested that expression of bcl-2 could provide pro tection against apoptosis induced by cytotoxic drugs via a mechanism which was different from the classical determinants of drug resistance. Sensitivity and resistance to inhibitors of thymidylate synthase (EC 2.1.1. 45) were chosen for study since these drugs have a well-defined and quantifiable locus of action with similarly...

The hypothesis was tested that expression of bcl-2 could provide pro tection against apoptosis induced by cytotoxic drugs via a mechanism which was different from the classical determinants of drug resistance. Sensitivity and resistance to inhibitors of thymidylate synthase (EC 2.1.1. 45) were chosen for study since these drugs have a well-defined and quantifiable locus of action with similarly...

Diazaquinomycin A (1), a new thymidylate (TMP) synthase inhibitor, is poorly soluble in various solvents and exhibits no antitumor activity, while a series of the analogues prepared from 1 are more soluble in water and chloroform than 1, and some of them exhibit antitumor activity in mice. Some analogues in which the lactam rings are replaced by pyridine rings did not inhibit TMP synthase. The ...

The cytotoxic effect of sequence and dose of Tomudex (TX) and 5-fluorouracil (FUra) on an HCT-8 colon carcinoma cell line using a clonogenic assay was evaluated. Synergistic cell kill was obtained with 24 h of exposure to TX followed by 4 h of exposure to FUra. Marginal synergy was obtained with the same sequence but with a 5-day exposure to FUra. The reverse sequence, FUra (either 4 h or 5 day...

Unlike mammalian cells, malarial parasites are completely dependent on the de novo pyrimidine pathway and lack the enzymes to salvage preformed pyrimidines. In the present study, first, it is shown that 1843U89, even without polyglutamylation, is a potent folate-based inhibitor of purified malarial parasite thymidylate synthase. The binding was noncompetitive with respect to methylenetetrahydro...