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BM 212 and its Derivatives as a New Class of Antimycobacterial Active Agents

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During our investigation in pyrrole antibacterial area we have identified a subclass with a good potent in vitro activity against mycobacteria and fungi. We have individuated the salient structural feature and BM 212 as lead for the class. SAR studies allowed us to synthesize several analogue derivatives. Some of them revealed more active than BM 212 against mycobacteria, but they lost antifungal activity. In particular the Protection Index (PI) was very interesting for some derivatives, comparable to that of reference compounds, Isoniazid (INH), Streptomycin (SM) and Rifampin (RF). Many of the synthesized compounds revealed active against intracellular mycobacteria and they showed to be inhibitory to drug-resistant mycobacteria of clinical origin. On the base of microbiological results we have hypothesized a pharmacophore model that was also optimized. The rational design, and the evaluation of the in vitro activity against mycobacteria are described.
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Keywords: BM 212; mycobacteria; ntimycobacterial Active Agents; pyrrole

Document Type: Review Article

Publication date: 2002-11-01

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