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

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. N...

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Published in:	Pharmaceuticals (Basel, Switzerland) Vol. 16; no. 8; p. 1120
Main Authors:	do Carmo Maquiaveli, Claudia, da Silva, Edson Roberto, Hild de Jesus, Barbara, Oliveira Monteiro, Caio Eduardo, Rodrigues Navarro, Tiago, Pereira Branco, Luiz Octavio, Souza dos Santos, Isabela, Figueiredo Reis, Nanashara, Portugal, Arieli Bernardo, Mendes Wanderley, João Luiz, Borges Farias, André, Correia Romeiro, Nelilma, de Lima, Evanoel Crizanto
Format:	Journal Article
Language:	English
Published:	Basel MDPI AG 01-08-2023 MDPI
Subjects:	ABC transporters Analysis anthranyl hydrazides arginase Biosynthesis Design Drug therapy Drugs Enzymes Leishmania Leishmaniasis Parasitic diseases Polyamines PTR1 Structure-activity relationship (Pharmacology) Structure-activity relationships Toxicity Tropical diseases Brazil
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Summary:	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 μM. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1424-8247 1424-8247
DOI:	10.3390/ph16081120