SAR Study of 4,8-Disubstituted Pyrimido[5,4-]pyrimidines Exhibiting Antitrypanosomal and Antileishmanial Activity.

A set of new derivatives of 4,8-disubstituted pyrimido[5,4-]pyrimidines were efficiently synthesized and evaluated against and promastigotes and intramacrophage amastigotes. The cytotoxicity was determined using the THP-1 cell line, and early ADME-Tox was carried out using assays for cytotoxicity (A549 and HEK293 cell lines) and CYP3A4 and hERG cardiotoxicity liabilities. All the new compounds were active against (0.

Veterinary perspectives on the urbanization of leishmaniosis in Morocco.

Background: Leishmaniosis caused by Leishmania infantum, L. major and L. tropica is endemic in Morocco.

Identification of Innovative Folate Inhibitors Leveraging the Amino Dihydrotriazine Motif from Cycloguanil for Their Potential as Anti- Agents.

Folate enzymes, namely, dihydrofolate reductase (DHFR) and pteridine reductase (PTR1) are acknowledged targets for the development of antiparasitic agents against Trypanosomiasis and Leishmaniasis. Based on the amino dihydrotriazine motif of the drug Cycloguanil (Cyc), a known inhibitor of both folate enzymes, we have identified two novel series of inhibitors, the 2-amino triazino benzimidazoles () and 2-guanidino benzimidazoles (), as their open ring analogues. Enzymatic screening was carried out against PTR1, DHFR, and thymidylate synthase (TS).

Exploring hydrophilic 2,2-di(indol-3-yl)ethanamine derivatives against Leishmania infantum.

Herein we report the design and the synthesis of a library of new and more hydrophilic bisindole analogues based on our previously identified antileishmanial compound URB1483 that failed the preliminary in vivo test. The novel bisindoles were phenotypically screened for efficacy against Leishmania infantum promastigotes and simultaneously for toxicity on human macrophage-like THP-1 cells. Among the less toxic compounds, eight bisindoles showed IC50 below 10 μM.