ABSTRACT
In an effort to discover potent antibacterials based on the entropically favored 'bioactive conformation' approach, a series of novel tricyclic molecules mimicking the conformationally constrained structure of Linezolid is reported. Based on the initial tricyclic molecule 1, the benzazepine derivative 2 was designed where the tricyclic structure had more flexibility around C-N bond compared to 1. While, the molecule 2 was less active, the molecule 3 showed promising antibacterial activity presumably after having obtained rigidity due to pyrrole ring. The syntheses, SAR studies, and evaluation of 3 as a lead compound are reported.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Oxazolidinones/chemical synthesis , Oxazolidinones/pharmacology , Anti-Bacterial Agents/pharmacology , Benzazepines/chemistry , Molecular Mimicry , Pyrroles/chemistry , Structure-Activity RelationshipABSTRACT
The success of strain improvement programme depends on the number of isolates that can be screened after mutagenic treatment. A technique to rapidly screen large number of high-yielding isolates was developed. The 'agar plug' method that utilizes the anti-fungal property of lovastatin to produce a zone of inhibition against Neurospora crassa was not only economical but also less labour-intensive. We were able to isolate a high-yielding strain, the productivity of which increased by 138% as compared to the parent strain in the submerged fermentation process.
Subject(s)
Aspergillus/metabolism , Biological Assay , Lovastatin/biosynthesis , Lovastatin/pharmacology , Neurospora crassa/drug effects , Agar , Aspergillus/genetics , Aspergillus/growth & development , Culture Media , Mycology/methods , Neurospora crassa/growth & developmentABSTRACT
Several 7-(3R,4R-N,N'-dialkyl diaminopyrrolidinyl)-substituted quinolones were synthesized and evaluated for antibacterial activities. 5-Amino-7-(3R,4R-N,N'-dimethyldiamino-6,8-difluoro-1,4-dihydro-1-c yclopropyl -4-oxoquinoline-3-carboxylic acid was found to have potent antibacterial activity against gram +ve organisms.