Synthesis and biological evaluation of 12 novel (-)-camphene-based 1,3,4-thiadiazoles against Mycobacterium tuberculosis.
Giovana Ferreira CostacurtaMariana Rp SouzaEloísa Gibin SampironAryadne L AlmeidaVanessa Pietrowski BaldinAndressa L IequeNathally C de S SantosPedro Hr AmaralCleuza C SilvaVera Lúcia Dias SiqueiraKatiany Rizzieri Caleffi FerracioliRosilene Fressatti CardosoFábio VandresenRegiane Bertin de Lima ScodroPublished in: Future microbiology (2020)
Aim: To evaluate the activity, cytotoxicity and efflux pumps inhibition of a series of 12 novels (-)-camphene-based 1,3,4-thiadiazoles (TDZs) against Mycobacterium tuberculosis (Mtb). Materials & methods: The minimum inhibitory concentration (MIC), cytotoxicity for three cell lines, ethidium bromide accumulation and checkerboard methods were carried out. Results: Compounds (6a, 6b, 6c, 6g, 6h and 6j) showed significant anti-Mtb activity (MIC 3.9-7.8 μg/ml) and no antagonism with anti-TB drugs already used in the TB treatment. Selectivity index (SI) was also determined, with values reaching 42.9 for H37Rv strain and 97.1 for clinical isolate. Five compounds also showed bacterial efflux pumps inhibition and one showed modulator effect with three drugs. Conclusion: These six TDZs should be considered as new scaffolds to develop anti-TB drugs.