ArticleMicroorganisms2026
Design, Synthesis, and Antitubercular Activity of Thiolutin-Cycloserine Hybrids: Reducing Cytotoxicity.
Article in Microorganisms, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The development of dual-acting hybrid antibiotics is a promising strategy to combat the ongoing spread of drug-resistant tuberculosis. Inspired by the structure of the natural dithiolopyrrolone hybrid antibiotic thiomarinol and based on the synergistic effects confirmed by checkerboard assays, we employed a molecular hybridization strategy. The dithiolopyrrolone natural product thiolutin was covalently linked to the pharmacophores of four clinical antitubercular drugs-cycloserine, linezolid, isoniazid, and pyrazinamide-through alkyl linkers of 7-10 carbon atoms via amide condensation, leading to the design and synthesis of 15 novel hybrids. In vitro antitubercular activity evaluation revealed that the cycloserine series exhibited the best activity, with MIC values as low as 1 μg/mL, followed by the isoniazid series. Cytotoxicity assays showed that all cycloserine hybrids had IC
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