RESUMO
Two series of novel AHL analogues were designed, synthesized and evaluated for antibacterial activity under cell membrane conditions in vitro. Analogues 4a-c and 4g-m presented potent activity against Gram-positive bacteria. Especially the analogue 4l exerted the most potent inhibition against Bacillus subtilis with MIC50 value of 1.443µg/ml. To our surprise, analogues 6a-c and 6g showed weak inhibition against Gram-negative bacteria with MIC50 values ranging from 17.589 to 67.840µg/ml. This was the first report about synthesis and antibacterial evaluation in vitro of AHL analogues containing dithioester linkage.
Assuntos
4-Butirolactona/análogos & derivados , Antibacterianos/síntese química , Desenho de Fármacos , 4-Butirolactona/síntese química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Carbamatos/síntese química , Carbamatos/química , Carbamatos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Percepção de Quorum/efeitos dos fármacosRESUMO
Two series of more available novel 1,2,3-triazole-Jaspine B hybrids were efficiently synthesized employing click chemistry approach and evaluated for their cytotoxic activities against three human cancer cell lines (EC-9706, MGC-803 and MCF-7). Among them, compound 14h showed excellent inhibition against MCF-7 (IC50 = 1.93 µM) and was more potent than 5-Fu and Jaspine B against all three cancer cell lines. Further investigation of apoptosis assay and cell cycle analysis demonstrated that compound 14h caused cellular early and late apoptosis and arrested the cell cycle at G2/M phase in a concentration- and time-independent manner. This was the first report about the synthesis and in vitro cytotoxic evaluation of 1,2,3-triazole-Jaspine B hybrids.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Esfingosina/análogos & derivados , Triazóis/química , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Humanos , Interações Hidrofóbicas e Hidrofílicas , Concentração Inibidora 50 , Esfingosina/químicaRESUMO
A series of steroidal[17,16-d]thiazole, steroidal[1,2-b]pyridine and steroidal[17,16-d]thiazole[2,1-b]imidazo products were synthesized through a convenient and productive method. Anti-proliferation activity against EC109 (human esophageal carcinoma), EC9706 (human esophageal carcinoma) and MGC-803 (human gastric carcinoma) cell lines was examined in vitro. Among the screened compounds, several highly potential compounds were located.