Synthesis and evaluation of some pyrimidine analogs against toxoplasmosis

Abstract

Toxoplasmosis is a worldwide infection caused by the obligate intracellular protozoan parasite Toxoplasma gondii. Some pyrimidine analogs were synthesized to be evaluated for their antitoxoplasma effects in animal experiments. Results were assessed by studying parasite density, estimation of serum Toxoplasma antigen, studying the ultrastructural changes of the parasite, and the histopathological changes of the affected organs and inhibitory activity for dihydrofolate reductase (DHFR) isolated from Cryptosporidium parvum. The result showed that 4 out of 12 synthesized compounds have promising antitoxoplasma potentials. The animals that received these four compounds showed statistically significant decrease in the mean number of the parasite count in the liver and the spleen when compared to the corresponding control group. Moreover, Toxoplasma antigen was very low or even absent in the serum of animals receiving these compounds. Light microscopic examination of the peritoneal exudates of animals receiving these compounds showed stoppage of movement and deformity in shape of the tachyzoites, whereas scanning electron microscopy revealed that the organisms had lost their crescent shape, with dimples and deep ridges on their surfaces. Very mild histopathological changes were noticed in liver, spleen, and lungs of the groups of animals receiving these compounds in comparison to the other groups. Thus, these compounds proved their effectiveness in eradication of the experimental Toxoplasma infection and inhibition of DHFR from C. parvum.

Synthesis of new 3,4-dihydropyrano[c]chromene derivatives and their evaluation as acetyl cholinesterase inhibitors

“…Refluxing compounds 8a-d with triethylorthoformate in acetic anhydride at reflux afforded the corresponding ethyl-N- The structures of products are characterized by 1 H NMR along with 13 C NMR are in agreement with the proposed structures.…”

“…1 H NMR (300 MHz) and 13 C NMR (75 MHz) spectra were recorded in deuterated CDCl3 and DMSO-d6 on a Bruker AC-300 using non-deuterated solvents as internal reference. All chemical shifts were reported as δ values (ppm) and coupling constants (J) were expressed in Hz.…”

“…After cooling, the mixture diluted with cold ethanol when a solid formed which collected by filtration, washed several times with cold ethanol and dried and recrystallized from ethanol to afford the chromenes 8a-d (Scheme 1). 13 …”

Synthesis and Characterization of Fully Substituted Pyrimidines by Using Ketene Dithioacetal as Potent Antimicrobial Agent

“…1 H (400 MHz) and 13 C (100 MHz) NMR spectra were recorded on a Bruker AVANCE II spectrometer in CDCl 3 . Chemical shifts are expressed in δ ppm downfield from TMS as an internal standard.…”

“…Particularly pyridine nucleus which is the important constructive part of many natural products and used as antimalarial [2], antitoxoplasma [3], fungicidal [4], antibacterial [5], anti-inflammatory and antitumor agent [6]. The Biginelli reaction [7] has been reported for the synthesis of many pyrimidine darivatives by the one-pot condensation of active methylene, urea and aldehydes.…”