RESUMEN
A series of diindolylmethanes (5a-t) were designed, synthesized, and examined for their cytotoxicity against four human cancer cell lines like prostate (DU-145), lung (A549), breast (MCF-7) and cervical cancer (HeLa). These results revealed that among all the hybrids, two (5k and 5r) were identified and exhibited significant cytotoxic effect against A549 cancer cells with IC50 values of 1.65⯱â¯0.3 and 1.80⯱â¯0.8⯵M respectively. To investigate the reasons for the cytotoxic activity, the conventional biological assays were carried out with 5k and 5r on the A549 cancer cells. Both hybrids led to the arrest of A549 cell lines at the G2/M phase of the cell cycle and strongly induced apoptosis. Further the apoptotic effects of 5k and 5r were confirmed by ROS, annexin-V FITC, and mitochondrial membrane potential. Moreover, structure-activity relationships were elucidated with various substitutions on these hybrids.
Asunto(s)
Apoptosis/efectos de los fármacos , Imidazoles/farmacología , Indoles/farmacología , Piridinas/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Imidazoles/química , Indoles/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Piridinas/química , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-ActividadRESUMEN
2-Styryl quinolines (9a-l) have been synthesized regioselectively from 2-methyl-quinoline by using NaOAc in water acetic acid binary solvents and evaluated for their antibacterial activity against both Gram-positive and Gram-negative strains. Among these, the compounds 12 and 8 were found to be active against both bacterial strains. Compounds 9b, 9f, 9g, 9i, 9j and 9k were the most active among the series exhibiting MIC values ranging between 1.9 and 31.2 µg ml(-1) against different bacterial strains. Compounds 9j and 9k were found to be as potent as the standard drug ciprofloxacin against Micrococcus luteus, Klebsiella planticola and Staphylococcus aureus. In addition, the compounds showed bactericidal activity; compound 9j was found to be better than ciprofloxacin, with an MBC value of 0.9 µg ml(-1) against both M. luteus and K. planticola. The compounds also inhibited biofilm formation, and compound 9j was found to be equipotent to erythromycin against M. luteus and S. aureus MLS16. Further, theoretical studies such as those on druggable properties and PMI plot have been carried out.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Simulación por Computador , Quinolinas/síntesis química , Quinolinas/farmacología , Antibacterianos/química , Bacterias/efectos de los fármacos , Biopelículas/efectos de los fármacos , Técnicas de Química Sintética , Aprobación de Drogas , Pruebas de Sensibilidad Microbiana , Quinolinas/química , Estereoisomerismo , Relación Estructura-Actividad , Especificidad por SustratoRESUMEN
Tankyrase 1 and 2 belonging to the family of poly(ADP-ribosyl)ases play an important role in PARsylation by utilizing NAD+ as a substrate in order to generate ADP-ribose polymers. Tankyrases are involved in a number of cellular functions, that includes telomere homeostasis, mitotic spindle formation, vesicle transport linked to glucose metabolism, Wnt/ß-catenin signalling, and viral replication. These roles of tankyrases in disease-relevant cellular processes have made them attractive drug targets. Recently, several inhibitors have been identified as potential clinical leads. The current review covers the progress, mechanism and binding modes of recently known Tankyrase inhibitors and discusses the rational approaches that were used to identify the tankyrase inhibitors.