Quinolone-isoniazid hybrids: synthesis and preliminary in vitro cytotoxicity and anti-tuberculosis evaluation

MedChemComm
2019.0

Abstract

Herein, we propose novel quinolones incorporating an INH moiety as potential drug templates against TB. The quinolone-based compounds bearing an INH moiety attached <i>via</i> a hydrazide-hydrazone bond were synthesised and evaluated against <i>Mycobacterium tuberculosis</i> H37Rv (MTB). The compounds were also evaluated for cytotoxicity against HeLa cell lines. These compounds showed significant activity (MIC<sub>90</sub>) against MTB in the range of 0.2-8 μM without any cytotoxic effects. Compounds <b>10</b> (MIC<sub>90</sub>; 0.9 μM), <b>11</b> (MIC<sub>90</sub>; 0.2 μM), <b>12</b> (MIC<sub>90</sub>; 0.8 μM) and compound <b>15</b> (MIC<sub>90</sub>; 0.8 μM), the most active compounds in this series, demonstrate activities on par with INH and superior to those reported for the fluoroquinolones. The SAR analysis suggests that the nature of substituents at positions -1 and -3 of the quinolone nucleus influences anti-MTB activity. Aqueous solubility evaluation and <i>in vitro</i> metabolic stability of compound <b>12</b> highlights favourable drug-like properties for this compound class.

Knowledge Graph

Similar Paper

Quinolone-isoniazid hybrids: synthesis and preliminary in vitro cytotoxicity and anti-tuberculosis evaluation
MedChemComm 2019.0
Design of hybrid molecules as antimycobacterial compounds: Synthesis of isoniazid-naphthoquinone derivatives and their activity against susceptible and resistant strains of Mycobacterium tuberculosis
Bioorganic &amp; Medicinal Chemistry 2019.0
Synthesis and antitubercular activity of 7-chloro-4-quinolinylhydrazones derivatives
Bioorganic &amp; Medicinal Chemistry Letters 2009.0
Design and synthesis of some new quinoline-3-carbohydrazone derivatives as potential antimycobacterial agents
Bioorganic &amp; Medicinal Chemistry Letters 2010.0
Identification of a novel class of quinoline–oxadiazole hybrids as anti-tuberculosis agents
Bioorganic &amp; Medicinal Chemistry Letters 2016.0
Design and synthesis of biquinolone–isoniazid hybrids as a new class of antitubercular and antimicrobial agents
European Journal of Medicinal Chemistry 2013.0
Design, development of new synthetic methodology, and biological evaluation of substituted quinolines as new anti-tubercular leads
Bioorganic &amp; Medicinal Chemistry Letters 2016.0
Synthesis and antitubercular activity of novel pyrazole–quinazolinone hybrid analogs
Medicinal Chemistry Research 2013.0
Development of antitubercular compounds based on a 4-quinolylhydrazone scaffold. Further structure–activity relationship studies
Bioorganic &amp; Medicinal Chemistry 2009.0
New 1,4-di-N-oxide-quinoxaline-2-ylmethylene isonicotinic acid hydrazide derivatives as anti-Mycobacterium tuberculosis agents
Bioorganic &amp; Medicinal Chemistry Letters 2011.0