RESUMEN
A series of pyrazolo[1,5-a]pyridine-3-carboxamide hybrids were designed and evaluated as novel anti-tubercular agents. The representative hybrid 7 exhibited promising in vitro activity against susceptive strain H37Rv and a panel of drug-resistant Mtb strains with MIC values of 0.006 µg/mL and ranged from 0.003 to 0.014 µg/mL, respectively. More importantly, the hybrid 7 also showed very low cytotoxicity, and could significantly reduce the mycobacterial burden in a mouse model infected with autoluminescent H37Ra strain, which may serve as a lead compound for further development of new anti-tubercular agents.
Asunto(s)
Antituberculosos/síntesis química , Piridinas/farmacología , Animales , Antituberculosos/farmacología , Muerte Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Farmacorresistencia Microbiana , Ratones , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Piridinas/síntesis químicaRESUMEN
A series of pyrazolo[1,5-a]pyridine-3-carboxamide derivatives were designed and synthesized as new anti-Mycobacterium tuberculosis (Mtb) agents. The compounds exhibit promising in vitro potency with nanomolar MIC values against the drug susceptive H37Rv strain and a panel of clinically isolated multidrug-resistant Mtb (MDR-TB) strains. One of the representative compounds (5k) significantly reduces the bacterial burden in an autoluminescent H37Ra infected mouse model, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.
