RESUMEN
A series of oxime ester-derivatives were prepared by utilizing the schizandrin (1), a major compound isolated from Schisandra grandiflora, which is deployed in different traditional system of medicine. The in vitro antiproliferative activities of the synthesized compounds were assessed against a selected panel of human cancer cell lines (A549, RKO P3, DU145 and Hela) and normal cell (HEK293). Several of these derivatives were found more potent in comparison to parent compound, schizandrin (1). Particularly, 4a and 4b demonstrated potent activity against DU-145 and RKOP3 cell lines with IC50 values of 3.42 µM and 3.35 µM respectively. To characterize the molecular mechanisms involved in antitumoral activity, these two compounds, 4a and 4b were selected for further studies. Cell cycle analysis revealed that both the compounds were able to induce apoptosis and cell cycle arrest at G0/G1 phase. To know the extent of apoptosis in DU145 and RKOP3 cell lines, Annexin V-FITC were performed. Moreover, the tubulin polymerization assay indicated that 4a and 4b exhibits potent inhibitory effect on the tubulin assembly. Molecular docking studies and competitive binding assay also indicated that 4a and 4b effectively bind at the colchicine binding site of the tubulin.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Ciclooctanos/farmacología , Lignanos/farmacología , Compuestos Policíclicos/farmacología , Moduladores de Tubulina/farmacología , Tubulina (Proteína)/metabolismo , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclooctanos/síntesis química , Ciclooctanos/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HEK293 , Humanos , Lignanos/síntesis química , Lignanos/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/química , Polimerizacion/efectos de los fármacos , Schisandra/química , Relación Estructura-Actividad , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/químicaRESUMEN
PURPOSE: To determine the cost efficiency and to compare the cost effectiveness of conventional extracapsular cataract surgery (ECCE) and phacoemulsification at three hospitals of the Malaysian Ministry of Health (MOH). METHODS: Patient demography, pre-operative visual acuity, intra-operative complications, post-operative complications and post-operative visual acuity were recorded for two hundred and forty seven of the 400 patients who underwent cataract surgery during a 2-week period. The cost of surgery, which included capital, staff and overhead, and patient care consumable costs were assessed prospectively in 8 randomly sampled patients over a 3-month period. Cost efficiency refers to cost per cataract surgery. Cost effectiveness refers to cost per successful cataract surgery. This is estimated by the ratio of cost efficiency to the proportion of successful cataract surgery. Successful surgery was defined as best-corrected visual acuity (BCVA) of better than 6/12 at 3 months post-operatively. RESULTS: Proportion of patients who had post-operative visual acuity of 6/12 or better was higher in phacoemulsification group (94%) than in the ECCE group (81%). Conventional extracapsular cataract surgery with intraocular lens implant costs RM3442 (USD 905.79) and phacoemulsification with intraocular lens implant costs RM4288 (USD 1128.42). DISCUSSION: There was no significant difference in cost effectiveness between ECCE and phacoemulsification. The cost of cataract surgery in the MOH hospital was found to be high due to the high overhead costs.