The Cytotoxicity and Mode of Action of 2,3,4-Trisubstituted Pyrroles and Related Derivatives in Human Tmolt4 Leukemia Cells

4-Carbechoxy-l-methyl-2-phenacyl-3-phenylpyrrole (9), 4-carbethoxy-2-(4-methoxybcnzoyl)-3-(4-methoxyphcnyl)pyrrole (10) and 2-(4-methoxybenzoyl)-3,4-bis-(4-methoxyphenyl)pyrrole (11) proved to be potent cytotoxic agents against the growth of murine and human leukemias and lymphomas. Selective toxicity was demonstrated against the growth of solid tumors, e.g. human adenocarcinoma of the colon SW480 and ileum HCT-8, glioma U-87-MG, and rat UMR-106 osteosarcoma. A mode of action study in Tmolt4 leukemia cells demonstrated that the agents inhibited de novo purine synthesis at the regulatory sites PRPP-amido transferase, IMP dehydrogenase as well as dihydrofolate reductase resulting in significant inhibition of DNA synthesis in 60 min. Other biochemical sites which were affected significantly were thymidylate synthetase, DNA polymerase a, RNA polymerases, nucleoside kinase and ribonucleoside reductase

Broad-scale patterns of body size in squamate reptiles of Europe and North America

Aim To document geographical interspecific patterns of body size of European and North American squamate reptile assemblages and explore the relationship between body size patterns and environmental gradients. Location North America and western Europe. Methods We processed distribution maps for native species of squamate reptiles to document interspecific spatial variation of body size at a grain size of 110 x 110 km. We also examined seven environmental variables linked to four hypotheses possibly influencing body size gradients. We used simple and multiple regression, evaluated using information theory, to identify the set of models best supported by the data. Results Europe is characterized by clear latitudinal trends in body size, whereas geographical variation in body size in North America is complex. There is a consistent association of mean body size with measures of ambient energy in both regions, although lizards increase in size northwards whereas snakes show the opposite pattern. Our best models accounted for almost 60% of the variation in body size of lizards and snakes within Europe, but the proportions of variance explained in North America were less than 20%. Main conclusions Although body size influences the energy balance of thermoregulating ectotherms, inconsistent biogeographical patterns and contrasting associations with energy in lizards and snakes suggest that no single mechanism can explain variation of reptile body size in the northern temperate zone