879-65-2Relevant articles and documents
Effect of a novel 5-HT3 receptor antagonist 4i, in corticosterone-induced depression-like behavior and oxidative stress in mice
Gupta, Deepali,Radhakrishnan, Mahesh,Kurhe, Yeshwant
, p. 95 - 102 (2015)
Stress in our daily life severely affects the normal physiology of the biological system. Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of depression-like behavior, which remains under diagnosed and poorly treated. Exogenous corticosterone (CORT) administration has been demonstrated to develop a depression model, which has shown to mimic HPA-axis induced depression-like state in rodents. In the present study, the effect of a novel 5HT3 receptor, 4i was examined on CORT induced depression in mice. CORT (30 mg/kg, subcutaneously) was given for 4-weeks to mice in control group, while mice in drug treated group were given 4i (0.5-1 mg/kg, intraperitoneally)/fluoxetine (as a positive control, 10 mg/kg), for the last 2-weeks of CORT dosing. Repeated CORT dosing caused depression-like behavior in mice as indicated by increased despair effects in forced swim test (FST) and anhedonia in sucrose preference test. In addition, CORT administration induced oxidative load in the brain with significant increase in pro-oxidant (lipid peroxidation and nitrite levels) markers and a substantial decline in anti-oxidant defense (catalase and reduced glutathione levels) system, indicating a direct effect of stress hormones in the induction of the brain oxidative damage. On the other hand, 4i and fluoxetine treatment reversed the CORT induced depressive-like deficits. Furthermore, 4i and fluoxetine prevented CORT induced oxidative brain insults, which may plausibly demonstrate one of the key mechanisms for antidepressant-like effects of the compounds. Thus, the study suggests that 5HT3 antagonist; 4i may be implicated as pharmacological intervention targeting depressive-like anomaly associated with HPA-axis dysregulation.
Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
Platte, Simon,Korff, Marvin,Imberg, Lukas,Balicioglu, Ilker,Erbacher, Catharina,Will, Jonas M.,Daniliuc, Constantin G.,Karst, Uwe,Kalinin, Dmitrii V.
supporting information, p. 3672 - 3690 (2021/08/07)
Herein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N-acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post-screening structure optimization, yielded a potent 7 nM inhibitor of FXIIa and a 25 nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N-acylated aminotriazoles exhibited anticoagulant properties in vitro influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N-acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.
Cationic porphyrin-quinoxaline conjugate as a photochemically triggered novel cytotoxic agent
Kumar, Dalip,Chandra Shekar,Mishra, Bhupendra,Kurihara, Ryohsuke,Ogura, Maiko,Ito, Takeo
, p. 3221 - 3224 (2013/06/27)
A novel cationic porphyrin-quinoxaline conjugate 8 was prepared in good yield by the coupling of activated quinoxaline carboxylic acid 5 with an appropriate aminoporphyrin. The UV-vis spectra of conjugate 8 with the addition of ctDNA shows substantial hyp
