N-Acylhydrazones as drugs

Sreekanth Thota; Daniel A Rodrigues; Pedro de Sena Murteira Pinheiro; Lídia M Lima; Carlos A M Fraga; Eliezer J Barreiro

doi:10.1016/j.bmcl.2018.07.015

N-Acylhydrazones as drugs

Bioorg Med Chem Lett. 2018 Sep 15;28(17):2797-2806. doi: 10.1016/j.bmcl.2018.07.015. Epub 2018 Jul 9.

Authors

Sreekanth Thota¹, Daniel A Rodrigues², Pedro de Sena Murteira Pinheiro², Lídia M Lima³, Carlos A M Fraga⁴, Eliezer J Barreiro⁵

Affiliations

¹ National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswaldo Cruz - Ministério da Saúde, Av. Brazil 4036 - Prédio da Expansão, 8° Andar - Sala 814, Manguinhos, 21040-361 Rio de Janeiro, RJ, Brazil; Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), PO Box 68023, 21941-902 Rio de Janeiro, RJ, Brazil. Electronic address: sthota@cdts.fiocruz.br.
² Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), PO Box 68023, 21941-902 Rio de Janeiro, RJ, Brazil.
³ Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), PO Box 68023, 21941-902 Rio de Janeiro, RJ, Brazil. Electronic address: lidia@lassbio.icb.ufrj.br.
⁴ Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), PO Box 68023, 21941-902 Rio de Janeiro, RJ, Brazil. Electronic address: cmfraga@ccsdecania.ufrj.br.
⁵ Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), PO Box 68023, 21941-902 Rio de Janeiro, RJ, Brazil. Electronic address: ejbarreiro@ccsdecania.ufrj.br.

PMID: 30006065
DOI: 10.1016/j.bmcl.2018.07.015

Abstract

Over the last two decades, N-acylhydrazone (NAH) has been proven to be a very versatile and promising motif in drug design and medicinal chemistry. Herein, we discuss the current and future challenges in the emergence of bioactive NAH-based scaffolds and to developing strategies to overcome the failures in drug discovery. The NAH-related approved drugs nitrofurazone, nitrofurantoin, carbazochrome, testosterone 17-enanthate 3-benzilic acid hydrazine, nifuroxazide, dantrolene, and azumolene are already used as therapeutics in various countries. PAC-1 is an NAH-based therapeutic agent that entered clinical trials in 2015. Another NAH-derived scaffold, LASSBio-294, is in preclinical trials. This review highlights the detailed comprehensive assessment and therapeutic landscape of bioactive NAH motif scaffolds in preclinical and clinical studies published to date and their promise and associated challenges in current and future drug discovery of NAH-based drugs that will progress to clinical use.

Keywords: Clinical trials; Drug discovery; Drugs; N-Acylhydrazone; Preclinical; Therapeutics.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / therapeutic use*
Drug Discovery
Humans
Hydrazones / chemistry
Hydrazones / therapeutic use*
Molecular Structure
Neoplasms / drug therapy*

Substances

Antineoplastic Agents
Hydrazones