ABSTRACT
Modifications at different positions on the aloperine molecule were performed to improve its anticancer activity and develop anticancer drugs. The in vitro anticancer activities of 44 synthesized compounds were evaluated. The effect of modification positions on anticancer activity was discussed and a structure-activity relationship analysis was established. A novel series of compounds with modifications at the N12 position showed much higher cytotoxicity than aloperine. Among them, compound 22 displayed promising in vitro anticancer activity against PC9 cells with a median inhibitory concentration (IC50) of 1.43 µM. The mechanism studies indicated that compound 22 induced cell apoptosis and cell cycle arrest in PC9 cells. These results demonstrate the potential of aloperine thiourea derivatives in anticancer activity.
Subject(s)
Antineoplastic Agents , Apoptosis , Drug Screening Assays, Antitumor , Piperidines , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Humans , Structure-Activity Relationship , Molecular Structure , Apoptosis/drug effects , Piperidines/pharmacology , Piperidines/chemistry , Piperidines/chemical synthesis , Drug Design , Quinolizidines/pharmacology , Quinolizidines/chemistry , Quinolizidines/chemical synthesis , Cell Line, Tumor , Cell Cycle Checkpoints/drug effectsABSTRACT
OBJECTIVE: To investigate the association between the alleles of human leukocyte antigens (HLA)-DRB1 and essential hypertension (EH) in the Hans living in Yunnan of China. METHODS: The alleles of HLA-DRB1 were typed by polymerase chain reaction-sequence specific primers (PCR-SSP) technique in samples from 83 patients with essential hypertension and 91 healthy controls. All of the subjects, their grandparents and grand-grandparents are Hans living in Yunnan of China. RESULTS: The frequency of DRB1*1501/2 in the EH patients (0.219) was significantly higher than that in the controls(0.060), chi quare=18.331, P<0.01. Relative risk (RR) was 4.46, and etiologic factor (EF) was 0.34. The frequency of DRB1*0901 significantly decreased in the group of patients with EH in comparison to the controls (0.081 versus 0.192) chi-square=8.704 P<0.05. RR was 0.41 and prevention factor(PF) was 0.19. CONCLUSION: HLA-DRB1*1501/2 is associated with the susceptibility to essential hypertension in the Yunnan Hans of China. DRB1*0901 may protect one from the disease.