RESUMO
A library of 175 dipeptidomimetics and tripeptidomimetics containing an α-amino boronic acid or boronate has been synthesized, and the activity toward Mycobacterium tuberculosis, Candida albicans, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa has been screened. Although there is no clear structure-activity relationship, several compounds exhibit promising activity against different pathogens.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Ácidos Borônicos/farmacologia , Peptidomiméticos/farmacologia , Antibacterianos/síntese química , Antifúngicos/síntese química , Ácidos Borônicos/síntese química , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Mimetismo Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Peptidomiméticos/síntese química , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Medical treatment for tuberculosis is complicated nowadays by the appearance of new multiresistant strains, and therefore, new antibiotics are in great need. Here, we report the synthesis and in vitro testing of a new class of highly selective antimicrobial boron-containing peptidomimetics with compounds exhibiting activity against Mycobacterium tuberculosis at ≤5 µg/mL. The new approach developed makes it possible to synthesize variously substituted ß-aminoboronic acids and their derivatives with a high level of diastereoselectivity.
Assuntos
Antituberculosos/química , Boro/química , Peptidomiméticos , Antituberculosos/síntese química , Antituberculosos/farmacologia , Ácidos Borônicos/síntese química , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacosRESUMO
The mol-ecule of the title compound, C(16)H(21)BO(2), comprises a chiral fused tricyclic system containing five-membered (1,3,2-dioxaborolane), six-membered (cyclo-hexa-ne) and four-membered (cyclo-butane) rings. The 1,3,2-dioxaborolane ring is almost planar (r.m.s. deviation = 0.035â Å), and the syn H and Me substituents at this ring are in an eclipsed conformation. The cyclo-hexane and cyclo-butane rings adopt sofa and butterfly conformations, respectively. The B atom has a trigonal-planar configuration (sum of the bond angles = 360.0°). The phenyl ring is practically coplanar with the 1,3,2-dioxaborolane ring [dihedral angle between the ring planes = 1.96â (8)°]. The absolute structure was determined from the known configuration of (+)-pinanediol which was used in the synthesis. In the crystal, weak C-Hâ¯π(Ph) inter-actions occur.
