Synthesis and biological evaluation of bis-N2,N2'-(4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccinodihydrazides

Meloddy H Manyeruke; Thendamudzimu Tshiwawa; Heinrich C Hoppe; Michelle Isaacs; Ronnett Seldon; Digby F Warner; Rui W M Krause; Perry T Kaye

doi:10.1016/j.bmcl.2019.126911

Synthesis and biological evaluation of bis-N²,N²'-(4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccinodihydrazides

Bioorg Med Chem Lett. 2020 Mar 1;30(5):126911. doi: 10.1016/j.bmcl.2019.126911. Epub 2019 Dec 19.

Authors

Meloddy H Manyeruke¹, Thendamudzimu Tshiwawa¹, Heinrich C Hoppe², Michelle Isaacs³, Ronnett Seldon⁴, Digby F Warner⁵, Rui W M Krause⁶, Perry T Kaye⁷

Affiliations

¹ Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa.
² Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
³ Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
⁴ Drug Discovery and Development Centre (H3-D), Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
⁵ Molecular Mycobacteriology Research Unit, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁶ Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa. Electronic address: R.Krause@ru.ac.za.
⁷ Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa. Electronic address: P.Kaye@ru.ac.za.

PMID: 31952962
DOI: 10.1016/j.bmcl.2019.126911

Abstract

A series of N²,N²'-bis[4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccino-hydrazides, containing 4-hydroxycoumarin, hydrazine and tartaric acid moieties, have been prepared and examined for possible biological activity. Several of these compounds exhibit promising HIV-1 integrase inhibition (IC₅₀ = 3.5 μM), and anti-T. brucei (32% viability) and anti-mycobacterial (Visual MIC90 = 15.63 μM) activity.

Keywords: 4-Hydroxycoumarins; Anti-mycobacterial; Anti-trypanosomal; HIV-1 integrase; Succinodihydrazides; Synthesis.

Publication types

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

MeSH terms

Antifungal Agents / chemical synthesis
Antifungal Agents / metabolism
Antifungal Agents / pharmacology*
Antitubercular Agents / chemical synthesis
Antitubercular Agents / metabolism
Antitubercular Agents / pharmacology*
Catalytic Domain
Coumarins / chemical synthesis
Coumarins / metabolism
Coumarins / pharmacology*
HIV Integrase / chemistry
HIV Integrase / metabolism
HIV Integrase Inhibitors / chemical synthesis
HIV Integrase Inhibitors / metabolism
HIV Integrase Inhibitors / pharmacology*
HIV-1 / enzymology
HeLa Cells
Humans
Hydrazines / chemical synthesis
Hydrazines / metabolism
Hydrazines / pharmacology*
Microbial Sensitivity Tests
Molecular Docking Simulation
Mycobacterium tuberculosis / drug effects
Protein Binding
Trypanocidal Agents / chemical synthesis
Trypanocidal Agents / metabolism
Trypanocidal Agents / pharmacology*
Trypanosoma brucei brucei / drug effects

Substances

Antifungal Agents
Antitubercular Agents
Coumarins
HIV Integrase Inhibitors
Hydrazines
Trypanocidal Agents
HIV Integrase
p31 integrase protein, Human immunodeficiency virus 1