Synthesis and biological evaluation of 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones

Emmanuel O Olawode; Roman Tandlich; Earl Prinsloo; Michelle Isaacs; Heinrich Hoppe; Ronnett Seldon; Digby F Warner; Vanessa Steenkamp; Perry T Kaye

doi:10.1016/j.bmcl.2019.05.001

Synthesis and biological evaluation of 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones

Bioorg Med Chem Lett. 2019 Jul 1;29(13):1572-1575. doi: 10.1016/j.bmcl.2019.05.001. Epub 2019 May 3.

Authors

Emmanuel O Olawode¹, Roman Tandlich², Earl Prinsloo³, Michelle Isaacs⁴, Heinrich Hoppe⁵, Ronnett Seldon⁶, Digby F Warner⁷, Vanessa Steenkamp⁸, Perry T Kaye⁹

Affiliations

¹ Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Rhodes University, Grahamstown, 6140, South Africa. Electronic address: [email protected].
² Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Rhodes University, Grahamstown, 6140, South Africa.
³ Department of Biotechnology, Rhodes University, Grahamstown, 6140, South Africa.
⁴ Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 6140, South Africa.
⁵ Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 6140, South Africa; Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown, 6140, South Africa.
⁶ Drug Discovery and Development Centre (H3-D), Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa.
⁷ Molecular Mycobacteriology Research Unit, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁸ Department of Pharmacology, University of Pretoria, Pretoria, South Africa.
⁹ Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown, 6140, South Africa; Department of Chemistry, Rhodes University, Grahamstown 6140, South Africa. Electronic address: [email protected].

PMID: 31080006
DOI: 10.1016/j.bmcl.2019.05.001

Abstract

A series of novel, substituted 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones have been prepared and shown to exhibit promising concentration-dependent activity against human SH-SY5Y cells, Plasmodium falciparum, Mycobacterium tuberculosis and P. aeruginosa. Substituent effects on observed bioactivity have been explored; the para-fluorophenyl derivative 3d exhibited activity across the range of the bioassays employed, indicating the potential of the 2-chloro-3-[(4-arylthiazol-2-yl)amino]-1,4-naphthoquinone scaffold in the development of novel, broad spectrum therapeutics.

Keywords: 2-Chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones; Anti-bacterial; Anti-malarial; Anti-tuberculosis; Cytotoxicity; HeLa cells.

Publication types

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

MeSH terms

Humans
Molecular Structure
Naphthoquinones / chemical synthesis*
Structure-Activity Relationship

Substances

Naphthoquinones
1,4-naphthoquinone