BACKGROUND The human protozoan parasites Leishmania are prototrophic for pyrimidines with the ability of both de novo biosynthesis and uptake of pyrimidines. METHODOLOGY/PRINCIPAL FINDINGS Five independent L. infantum mutants were selected for resistance to the pyrimidine analogue 5-fluorouracil (5-FU) in the hope to better understand the metabolism of pyrimidine in Leishmania. Analysis of th...

Enzymatic synthesis of carbamoyl phosphate Carbamoyl phosphate is synthesized irreversibly by carbamoyl-phosphate synthase (CPS; EC6.3.4.16 and EC 6.3.5.5) in the first step of the routes of biosynthesis of pyrimidines, arginine and urea. In most bacteria, including Escherichia cofi, the same CPS is used for arginine and pyrimidine synthesis, whereas in higher organisms different CPS enzymes ar...

Numerous DNA mismatches and lesions activate MutS homologue (MSH) ATPase activity that is essential for mismatch repair (MMR). We have found that a mismatch embedded in a nearest-neighbor sequence context containing symmetric 3'-purines (2 x 3'-purines) enhanced, whereas symmetric 3'-pyrimidines (2 x 3'-pyrimidines) reduced, hMSH2-hMSH6 ATPase activation. The 3'-purine/pyrimidine effect was mos...

The Mannich reaction of 7-aryl-5,6-dihydropyrido[2,3-d]pyrimidines 3, easily accessible by condensation of 6-amino-1,3-dimethyluracil (1) with Mannich bases 2a – c, gives rise to a mixture of 7-aryl-6-(N,N-dimethylaminomethyl)pyrido[2,3-d]pyrimidines 6 and 7 as well as 1,2-bis(7-arylpyrido[2,3-d]pyrimidin-6-yl)ethane 13 the ratio of which depends on the reaction conditions and the amine used. 6...

In continuation to our research program concerned with structural modification of thieno[2,3-d]pyrimidines with the purpose of enhancing their anticancer activity, various series of hexahydrocycloocta[4,5]thieno[2,3-d]pyrimidin-4-ones, hexahydrocycloocta[4,5]thieno[3,2-e]-1,2,4triazolo[4,3-c]pyrimidine-3(2H)-thiones and 4-substituted hydrazinylhexahydrocycloocta[4,5]thieno[2,3-d]pyrimidines wer...

Non-nucleoside analogs of the pyrrolopyrimidine nucleosides toyocamycin, sangivamycin and thiosangivamycin have been synthesized and their cytotoxicity in mammalian cells determined. While studying the effects of 5-thioamide-substituted analogs on cell growth, we observed an interesting phenomenon in which cells recovered spontaneously from growth inhibition during extended incubations. HPLC st...

We report a novel and general method to access highly under-studied privileged scaffold—pyrimidines bearing trifluoroborate at C4, highlight the broad utility of these intermediates in rich array downstream functionalization reactions. This chemistry is underpinned by unique features group; its robustness provides an opportunity carry out chemoselective reactions other positions on pyrimidine w...