90766-96-4Relevant articles and documents
Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
Bai, Feifei,Fang, Jianguo,Song, Zi-Long,Zhang, Baoxin
, p. 2214 - 2231 (2020/03/06)
Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine-or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
Biology-oriented drug synthesis (BIODS): In vitro β-glucuronidase inhibitory and in silico studies on 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives
Salar, Uzma,Khan, Khalid Mohammed,Taha, Muhammad,Ismail, Nor Hadiani,Ali, Basharat,Qurat-ul-Ain,Perveen, Shahnaz,Ghufran, Mehreen,Wadood, Abdul
, p. 1289 - 1299 (2016/12/06)
Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1'-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS,1H -NMR and13C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50= 1.20 ± 0.01–60.30 ± 1.40 μM as compared to the standard D-saccharic acid 1,4-lactone (IC50= 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9–19, and 21–24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
Indium-mediated one-pot synthesis of benzoxazoles or oxazoles from 2-nitrophenols or 1-aryl-2-nitroethanones
Lee, Jung June,Kim, Jihye,Jun, Young Moo,Lee, Byung Min,Kim, Byeong Hyo
experimental part, p. 8821 - 8831 (2009/12/26)
One-pot reduction-triggered heterocyclizations from 2-nitrophenols to benzoxazoles and from 1-aryl-2-nitroethanones to oxazoles were investigated. In the presence of indium/AcOH in benzene at reflux, 2-nitrophenols and R-C(OMe)3 (R=H, Me, Ph) produced excellent yields of corresponding benzoxazoles within an hour. Similarly, 1-aryl-2-nitroethanones and Ph-C(OMe)3 in the presence of indium/AcOH in acetonitrile transformed into the corresponding oxazoles with good yields.
Stability studies of N-acylimidazoles
Zaramella, Simone,Stroemberg, Roger,Yeheskiely, Esther
, p. 2633 - 2639 (2007/10/03)
Studies of the stabilities of a series of N-acylimidazoles towards acidic and basic conditions of potential usefulness for the removal of common temporary protection in peptide and oligonucleotide synthesis are presented. N-Acylimidazoles with a variety of substituents in the acyl component were prepared and treated with 3% trifluoroacetic acid (TFA) in chloroform and with 2% 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in N,N-dimethylformamide (DMF), the extent of their degradation being determined by proton NMR. N-(2,4,6-Trimethylbenzoyl)imidazole (1) and N-(2,6-dimethoxybenzoyl)-imidazole (2) remained unaffected under the above acidic and basic conditions after 4 d and 2 d, respectively. In addition, 1 and 2 were resistant to treatment with a solution of 2% piperidine/2% DBU in DMF for 24 h. Under ammonolytic conditions, 2 was rapidly cleaved (less than 1 h), whereas 1 was 64% degraded after 48 h, as ascertained by reversed-phase HPLC. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.
