Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10.6 million new cases and 1.4 million deaths in 2021. This global emergency is exacerbated by the emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB; therefore, new drugs and new drug targets are urgently required. From a whole cell phenotypic screen, a series of azetidines derivatives termed BGAz, which elicit potent bactericidal activity with MIC₉₉ values <10 μM against drug-sensitive Mycobacterium tuberculosis and MDR-TB, were identified. These compounds demonstrate no detectable drug resistance. The mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from the existing mycobacterial cell wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as antitubercular chemotherapies.

A library of substituted indolo[2,3-c]quinolone-6-ones was developed as simplified Lamellarin isosters. Synthesis was achieved from indole after a four-step pathway sequence involving iodination, a Suzuki-Miyaura cross-coupling reaction, and a reduction/lactamization sequence. The inhibitory activity of the 22 novel derivatives was assessed on Haspin kinase. Two of them possessed an IC₅₀ of 1 and 2 nM with selectivity towards a panel of 10 other kinases including the parent kinases DYRK1A and CLK1. The most selective compound exerted additionally a very interesting cell effect on the osteosarcoma U-2 OS cell line.

The emergence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) necessitates novel therapeutics with distinct mechanisms. Here, we report amino-pyrazoline derivatives as a new class of dual-functional antimycobacterial agents, integrating potent bactericidal activity with fluorescence-based bacterial imaging. Initial screening identified AP-07 as a promising hit compound (MIC₉₉: 40 μM against Mycobacterium smegmatis, 49 μM against Mycobacterium bovis BCG). Structure-based optimization led to the discovery of AP-02 and AP-05 as lead compounds, with enhanced activity (MIC₉₉: 13-16 μM against M. smegmatis; 20-25 μM against M. bovis BCG). Additionally, spontaneous resistance assays detected no resistant colonies, suggesting a low risk of resistance development. Mechanistic studies confirmed Ag85C as the primary molecular target, disrupting late-stage mycolic acid biosynthesis and impairing cell wall integrity. Notably, pyrazoline derivatives exhibit intrinsic fluorescence, selectively labeling intracellular mycobacteria while remaining non-toxic to host macrophages, enabling real-time bacterial imaging. This work establishes fluorescent amino-pyrazolines as a promising foundation for next-generation antitubercular agents, bridging diagnostics and therapy in tuberculosis drug discovery.

This study reports the exclusive and rapid synthesis of twenty-four derivatives of 1-((mono/bis)trifluoromethyl)phenyl-3-(4-arylthiazol-2-yl)thioureas (series 7, 9 and 11), along with their antimicrobial activities against Candida albicans, Mycobacterium smegmatis and seven additional bacterial strains. The anticancer potential of these compounds was evaluated against various human cancer cell lines, including A549 (lung adenocarcinoma), HeLa (cervical carcinoma), IMR32 (neuroblastoma), MCF-7 (breast adenocarcinoma), HCT116 (colon cancer) and DU145 (prostate cancer). Among these, 1-(3,5-bistrifluoromethylphenyl)-3-(thiazol-2-yl)thiourea (7i) and 1-(4-trifluoromethylphenyl)-3-(4-(3-chlorophenyl)thiazol-2-yl)thiourea (11h) demonstrated significant antimicrobial activity against M. luteus, S. aureus, S. aureus 1 and C. albicans. Additionally, 1-(4-(3-chlorophenyl)thiazol-2-yl)-3-(3-trifluoromethylphenyl)thiourea (9g) and 1-(4-trifluoromethylphenyl)-3-(4-(2-fluorophenyl)thiazol-2-yl)thiourea (11g) showed activity against Mycobacterium smegmatis. The bioassay tests indicated that many of the thiourea derivatives exhibited moderate activity against the A549, HeLa, MCF-7 and HCT116 cancer cell lines.

Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10 million new cases and 1.5 million deaths in 2019. This global emergency is exacerbated by the emergence of multi-drug-resistant MDR-TB and extensively-drug-resistant XDR-TB, therefore new drugs and new drug targets are urgently required. From a whole-cell phenotypic screen a series of azetidines derivatives termed BGAz, that elicit potent bactericidal activity with MIC ₉₉ values <10 μM against drug-sensitive Mycobacterium tuberculosis and MDR-TB were identified. These compounds demonstrate no detectable drug resistance. Mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from existing mycobacterial cell-wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as anti-tubercular chemotherapies.

Thiazolyl-benzene/camphor sulfonamide derivatives (series 4a–k, 5a–j and 6a–i) were synthesized by reaction of various aryl sulfonyl chlorides and camphor sulfonyl chlorides with 2-amino-4-phenylthiazole. The compounds were evaluated for antibacterial, antioxidant, and α-glucosidase/α-amylase inhibitory activities. Biological screening showed that 4h, 5g and 5i displayed significant activity against most Gram-positive bacteria (MICs 4.68–18.75 µg/mL), while 4b and 5i were active against most Gram-negative bacteria with similar MIC ranges. In the DPPH assay, 4e, 4f, 4g and 4h exhibited slightly stronger radical-scavenging activity than ascorbic acid (IC₅₀ ≈ 3.5–3.8 µM vs. 4.14 µM); 5f emerged as the best dual carbohydrate-digesting enzyme inhibitor, and 5b and 5e demonstrated selectivity toward α-amylase.