RESUMO
A series of aminoalcohols were synthesized by reaction of aminolysis of camphor derived oxiranes with chosen amines. The compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. Ten of the new structures show much higher activity than the classical anti-TB drug ethambutol. Some of the most active compounds were tested against MDR strain 43, and four of them demonstrated excellent activities with MICs 0.27-0.72 µM. The cytotoxicity of representative exerting antimycobacterial activity compounds was assessed. Quantitative structure-activity relationship (QSAR) model is derived to estimate the contribution of each structural fragment to the activity. The camphane-based aminoalcohols are promising lead compounds for further development of novel antimycobacterial agents.
Assuntos
Amino Álcoois/farmacologia , Antituberculosos/farmacologia , Canfanos/química , Mycobacterium tuberculosis/efeitos dos fármacos , Amino Álcoois/síntese química , Amino Álcoois/química , Antituberculosos/síntese química , Antituberculosos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Relação Quantitativa Estrutura-AtividadeRESUMO
In the title compound, C(16)H(13)NO, the mol-ecules are connected three-dimensionally through non-classical C-Hâ¯O and C-Hâ¯π inter-actions of 3.272â (3), 3.380â (3) and 3.382â (4)â Å. Classical hydrogen bonds are not observed. The dihedral angle between the benzyl and quinolin-2(1H)-one mean planes is 87.15â (7)°
