Dataset Information

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

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 via a hydrazide-hydrazone bond were synthesised and evaluated against Mycobacterium tuberculosis H37Rv (MTB). The compounds were also evaluated for cytotoxicity against HeLa cell lines. These compounds showed significant activity (MIC90) against MTB in the range of 0.2-8 ?M without any cytotoxic effects. Compounds 10 (MIC90; 0.9 ?M), 11 (MIC90; 0.2 ?M), 12 (MIC90; 0.8 ?M) and compound 15 (MIC90; 0.8 ?M), 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 in vitro metabolic stability of compound 12 highlights favourable drug-like properties for this compound class.

SUBMITTER: Beteck RM

PROVIDER: S-EPMC6390685 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Beteck Richard M RM Seldon Ronnett R Jordaan Audrey A Warner Digby F DF Hoppe Heinrich C HC Laming Dustin D Legoabe Lesetja J LJ Khanye Setshaba D SD

MedChemComm 20190111 2

Herein, we propose novel quinolones incorporating an INH moiety as potential drug templates against TB. The quinolone-based compounds bearing an INH moiety attached via a hydrazide-hydrazone bond were synthesised and evaluated against Mycobacterium tuberculosis H37Rv (MTB). The compounds were also evaluated for cytotoxicity against HeLa cell lines. These compounds showed significant activity (MIC90) against MTB in the range of 0.2-8 μM without any cytotoxic effects. Comp ...[more]

PMID: 30881619

Similar Datasets

Project description:BackgroundPrevention and treatment of chronic inflammatory diseases require effective and low-toxic medicines. Molecular hybridization is an effective strategy to enhance the biological activity of new compounds. Triterpenoid scaffolds are in the focus of attention owing to their anti-inflammatory, antiviral, antiproliferative, and immunomodulatory activities. Heteroprostanoids have different pleiotropic effects in acute and chronic inflammatory processes.ObjectiveThe study aimed to develop structurally new and low toxic anti-inflammatory agents via hybridization of betulinic acid with azaprostanoic acids.MethodsA series of betulinic acid-azaprostanoid hybrids was synthesized. The synthetic pathway included the transformation of betulin via Jones' oxidation into betulonic acid, reductive amination of the latter and coupling obtained by 3β-amino-3-deoxybetulinic acid with the 7- or 13-azaprostanoic acids and their homo analogues. The hybrids 1-9 were investigated in vivo on histamine-, formalin- and concanavalin A-induced mouse paw edema models and two models of pain - the acetic acid-induced abdominal writhing and the hotplate test. The hybrids were in vitro evaluated for cytotoxic activity on cancer (MCF7, U- 87 MG) and non-cancer humane cell lines.ResultsIn the immunogenic inflammation model, the substances showed a pronounced anti-inflammatory effect, which was comparable to that of indomethacin. In the models of the exudative inflammation, none of the compounds displayed a statistically significant effect. The hybrids produced weak or moderate analgesic effects. All the agents revealed low cytotoxicity on human immortalized fibroblasts and cancer cell lines compared with 3β- amino-3-deoxybetulinic acid and doxorubicin.ConclusionThe results indicate that the principal anti-inflammatory effect of hybrids is substantially provided with the triterpenoid scaffold and in some cases with the azaprostanoid scaffold, but the latter makes a significant contribution to reducing the toxicity of hybrids. Hybrid 1 is of interest as a potent low toxic agent against immune-mediated inflammation.

Dataset Information

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

Publications

Quinolone-isoniazid hybrids: synthesis and preliminary <i>in vitro</i> cytotoxicity and anti-tuberculosis evaluation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets