Design and Synthesis of New Anthranyl Phenylhydrazides: Antileishmanial Activity and Structure-Activity Relationship

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Maquiaveli, Claudia do Carmo ; da Silva, Edson Roberto ; de Jesus, Barbara Hild ; Monteiro, Caio Eduardo Oliveira ; Navarro, Tiago Rodrigues ; Branco, Luiz Octavio Pereira ; dos Santos, Isabela Souza ; Reis, Nanashara Figueiredo ; Portugal, Arieli Bernardo ; Wanderley, Joao Luiz Mendes ; Farias, Andre Borges ; Romeiro, Nelilma Correia ; de Lima, Evanoel Crizanto

• Document type: Journal article
• Source: PHARMACEUTICALS; v. 16, n. 8, p. 10-pg., 2023-08-01.

Abstract

Leishmaniasis is a neglected tropical disease affecting millions of people worldwide. A centenary approach to antimonial-based drugs was first initiated with the synthesis of urea stibamine by Upendranath Brahmachari in 1922. The need for new drug development led to resistance toward antimoniates. New drug development to treat leishmaniasis is urgently needed. In this way, searching for new substances with antileishmanial activity, we synthesized ten anthranyl phenylhydrazide and three quinazolinone derivatives and evaluated them against promastigotes and the intracellular amastigotes of Leishmania amazonensis. Three compounds showed good activity against promastigotes 1b, 1d, and 1g, with IC50 between 1 and 5 mu M. These new phenylhydrazides were tested against Leishmania arginase, but they all failed to inhibit this parasite enzyme, as we have shown in a previous study. To explain the possible mechanism of action, we proposed the enzyme PTR1 as a new target for these compounds based on in silico analysis. In conclusion, the new anthranyl hydrazide derivatives can be a promising scaffold for developing new substances against the protozoa parasite. (AU)

• FAPESP's process: 19/23769-4 - Rational drug design, synthesis, and study of the structure-activity relationship of Leishmania amazonensis arginase enzyme inhibitors for the development of new drugs
• Grantee: Edson Roberto da Silva
• Support Opportunities: Regular Research Grants