A novel series of sorafenib analogs containing 2-picolinyl hydrazide moiety were designed and synthesized. In vitro, most of synthesized compounds have antiproliferation activity on MDA-MB-231, ACHN, HepG2, Mia-PaCa-2 and SW1990 cell lines tested by MTT assay. It is worth noting that the antitumor activities of compounds 2c, 2d and 2f are more potent than that of sorafenib on pancreatic cancer cells Mia-PaCa-2 and SW1990, and the activities of compounds 3f and 3g are 2-3 times than that of sorafenib on human hepatocellular carcinoma HepG2 cell line.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Design ; Drug Screening Assays, Antitumor ; Humans ; Molecular Structure ; Niacinamide ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Phenylurea Compounds ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

OBJECTIVETo understand the environmental risk factors on attempted suicide in patients with major depression, and to study the interaction between factors as single nucleotide polymorphism(SNP) of TPH2 gene rs7305115 associated to attempted suicide in major depression.

METHODSPaired case-control study on 215 suicide attempters with major depression (92 male, 123 female) and molecular biological techniques were used to study the relation between TPH2 gene rs7305115 SNP,interrelated environmental factors and the rate of attempted suicide. Controls were paired with cases according to the same gender, similar age (no more than 3 years) and from the same district.

RESULTSThere were remarkably significant differences in gene types and gene frequency between case and control groups (P < 0.001). Data from multivariate conditional logistic regression model analysis showed that hopelessness, negative life-events and family history of suicide were relationship of attempted suicide in patients with major depression with OR values as 0.33 (95% CI: 0.22-0.99), 7.68 (95% CI: 5.79-13.74), 6.64 (95% CI: 2.48-11.04), 2.98 (95% CI: 1.17-5.04) respectively. There was no first level interaction between any of the two risk factors.

CONCLUSIONResults from the study supported the idea that hopelessness, negative life-events and family history of suicide were risk factors of attempted suicide in major deprbssion while TPH2 gene rs7305115 A/A might be the protective factor.

Case-Control Studies ; China ; epidemiology ; Depressive Disorder, Major ; genetics ; psychology ; Humans ; Odds Ratio ; Polymorphism, Single Nucleotide ; Risk Factors ; Suicide, Attempted ; psychology ; statistics & numerical data ; Tryptophan Hydroxylase ; genetics

Glucokinase (GK) is a new target for the treatment of type II diabetes mellitus (T2DM). In order to find a structure-simplified small molecule GK activator, 19 salicylic acid derivatives were designed and synthesized based on new lead compound (1). Experimental results showed that the potency of compound 8h is superior to control RO-28-0450 in GK activation.
Drug Design ; Enzyme Activation ; drug effects ; Enzyme Activators ; chemical synthesis ; chemistry ; pharmacology ; Glucokinase ; metabolism ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Salicylates ; chemical synthesis ; chemistry ; pharmacology ; Thiazoles ; pharmacology