Hameed P, Shahul; Raichurkar, Anandkumar; Madhavapeddi, Prashanti; Menasinakai, Sreenivasaiah; Sharma, Sreevalli; Kaur, Parvinder; Nandishaiah, Radha; Panduga, Vijender; Reddy, Jitendar; Sambandamurthy, Vasan K.; Sriram, D. published the artcile< Benzimidazoles: Novel Mycobacterial Gyrase Inhibitors from Scaffold Morphing>, Formula: C5H6FN3, the main research area is benzimidazole DNA gyrase inhibitor scaffold morphing Mycobacterium; DNA gyrase; NBTIs; Tuberculosis; aminopiperidines; benzimidazoles; type II topoisomerases.
Type II topoisomerases are well conserved across the bacterial species, and inhibition of DNA gyrase by fluoroquinolones has provided an attractive option for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis (Mtb) poses a threat for its sustainability. A scaffold hopping approach using the binding mode of novel bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity. Docking of benzimidazoles to a NBTI bound crystal structure suggested that this class of compound makes key contacts in the enzyme active site similar to the reported NBTIs. This observation was further confirmed through the measurement of DNA gyrase inhibition, and activity against Mtb strains harboring mutations that confer resistance to aminopiperidines based NBTIs and Mtb strains resistant to moxifloxacin. Structure-activity relationship modification at the C-7 position of the left-hand side ring provided further avenue to improve hERG selectivity for this chem. series that has been the major challenges for NBTIs.
ACS Medicinal Chemistry Letters published new progress about DNA gyrases Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (inhibitors). 212268-13-8 belongs to class pyridine-derivatives, and the molecular formula is C5H6FN3, Formula: C5H6FN3.