Assay Development for High-Throughput Drug Screening Against Mycobacteria.

Mycobacterium abscessus (Mab) infections are challenging to treat due to high intrinsic drug resistance, comparable to multidrug-resistant tuberculosis. Treatments are extremely ineffective and based on a multi-drug regimen, resulting in low patient compliance. Consequently, the scientific community is urged to identify new and effective drugs to treat these infections.

A high-throughput target-based screening approach for the identification and assessment of mycothione reductase inhibitors.

Unlabelled: The World Health Organization's goal to combat tuberculosis (TB) is hindered by the emergence of anti-microbial resistance, therefore necessitating the exploration of new drug targets. Multidrug regimens are indispensable in TB therapy as they provide synergetic bactericidal effects, shorten treatment duration, and reduce the risk of resistance development. The research within our European RespiriTB consortium explores energy metabolism to identify new drug candidates that synergize with bedaquiline, with the aim of discovering more efficient combination drug regimens.

Expanding the squaramide library as mycobacterial ATP synthase inhibitors: Innovative synthetic pathway and biological evaluation.

Mycobacterial ATP synthase is a validated therapeutic target for combating drug-resistant tuberculosis. Inhibition of this enzyme has been featured as an efficient strategy for the development of new antimycobacterial agents against drug-resistant pathogens. In this study, we synthesised and explored two distinct series of squaric acid analogues designed to inhibit mycobacterial ATP synthase.

Design, Synthesis, and Antimycobacterial Evaluation of Novel Tetrahydroisoquinoline Hydrazide Analogs.

A series of novel 2-substituted-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carbohydrazide were designed, synthesized and structures were confirmed by analytical methods, viz., H-NMR, C-NMR and Mass spectrometry. Synthesized derivatives were evaluated for their anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Ra.

Design, synthesis and biological evaluation of benzo-[]-imidazo-[2,1-]-thiazole and imidazo-[2,1-]-thiazole carboxamide triazole derivatives as antimycobacterial agents.

In the search for new anti-mycobacterial agents, we revealed the importance of imidazo-[2,1-]-thiazole and benzo-[]-imidazo-[2,1-]-thiazole carboxamide derivatives. We designed, ADMET predicted and synthesized four series of novel imidazo-[2,1-]-thiazole and benzo-[]-imidazo-[2,1-]-thiazole carboxamide analogues in combination with piperazine and various 1,2,3 triazoles. All the synthesized derivatives were characterized by H NMR, C NMR, HPLC and MS spectral analysis and evaluated for antitubercular activity.

Design, Synthesis and Biological Evaluation of Novel Spiro-[Chroman-2,4'-Piperidin]-4-One Analogs as Anti-Tubercular Agents.

A series of novel spiro-[chromane-2,4'-piperidin]-4(3H)-one derivatives were designed, synthesized and structures were confirmed by analytical methods, viz., H-NMR, C-NMR and mass spectrometry. The synthetic derivatives were evaluated for their anti-tuberculosis (anti-TB) activity against Mycobacterium tuberculosis (Mtb) strain H37Ra.

Correction: Seeking potent anti-tubercular agents: design and synthesis of substituted--(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives as anti-tubercular agents.

[This corrects the article DOI: 10.1039/D0RA01348J.].

Seeking potent anti-tubercular agents: design and synthesis of substituted--(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives as anti-tubercular agents.

Pyrazinamide is an important first-line drug used in shortening TB therapy. In our current work, a series of novel substituted--(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives were designed, synthesized, and evaluated for their anti-tubercular activity against H37Ra. Among the tested compounds, five compounds (6a, 6e, 6h, 6j and 6k) from Series-I and one compound (7e) from Series-II exhibited significant activity against H37Ra with 50% inhibitory concentrations (IC) ranging from 1.

The synthesis and in vitro biological evaluation of novel fluorinated tetrahydrobenzo[j]phenanthridine-7,12-diones against Mycobacterium tuberculosis.

Tuberculosis (TB) still has a major impact on public health. In order to efficiently eradicate this life-threatening disease, the exploration of novel anti-TB drugs is of paramount importance. As part of our program to design new 2-azaanthraquinones with anti-mycobacterial activity, various "out-of-plane" tetrahydro- and octahydrobenzo[j]phenanthridinediones were synthesized.