Pyrimido[5,4-d]pyrimidine-Based Compounds as a Novel Class of Antitrypanosomal and Antileishmanial Agents

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Lopes, A (Author) Other; Santarem, N (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Carvalho, MA (Author) Other

Journal

Title: Acs Medicinal Chemistry Letters

Vol. 13

Pages: 1427-1433

ISSN: 1948-5875

Publisher: American Chemical Society

Indexing

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Other information

Authenticus ID: P-00X-32Z

DOI: 10.1021/acsmedchemlett.2c00170

Abstract (EN): Sleeping sickness and leishmaniasis are neglected tropical diseases that threaten millions of people. The currently available therapies present several limitations, including high toxicity, lack of efficacy, and emerging drug resistance, prompting a search for novel therapeutic agents. In this work, we designed, synthesized, and in vitro evaluated the activity of new pyrimido[5,4-d]pyrimidines against Trypanosoma brucei and Leishmania infantum (promastigote and amastigote forms). The cytotoxicity of the compounds against the THP1 cell line was also assessed. Most tested compounds presented low micromolar activity against T. brucei with IC50 values in the range between 0.9 and 13.4 mu M, and one compound also showed activity against L. infantum (IC50 = 3.13 mu M). Several molecules presented a selectivity index higher than 10. The most active compound against booth parasites is derivative 4c, with IC50 = 0.94 mu M (SI > 107) against T. brucei and IC50 = 3.13 mu M (SI > 32) against L. infantum. This data enabled the identification of a new promising molecular scaffold for developing a novel class of antitrypanosomal and antileishmanial agents.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7