Bioorganic and Medicinal Chemistry p. 1971 - 1985 (2018)
Update date:2022-08-15
Topics:
Meira, Cássio S.
dos Santos Filho, José Maurício
Sousa, Caroline C.
Anjos, Pamela S.
Cerqueira, Jéssica V.
Dias Neto, Humberto A.
da Silveira, Rafael G.
Russo, Helena M.
Wolfender, Jean-Luc
Queiroz, Emerson F.
Moreira, Diogo R.M.
Soares, Milena B.P.
4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.
View MoreSanming Coffer Fine Chemical Industrial Co., Ltd
website:http://www.cofferxm.com/
Contact:+86-598-5853979
Address:Jin-sha Yuan Chuang-ye Park,Hi-Tech Development Zone,Sanming City P.R.China
Hebei Fulong Import & Export Co., Ltd.
Contact:86-311-87795661
Address:15A19 Zhongyuan Building,368 Youyi North Street,Shijiazhuang 050070,China
Contact:+49-9398-993127
Address:Untertorstr. 27
Lianyungang Yunbo Chemical Co.,Ltd.
Contact:518-81066110
Address:B907,Dongsheng"Mingdu Square,21-2 East Chaoyang Road,Xinpu,(sale department)
Tianjin Emulsion Science&Technology Development Co.,Ltd
Contact:13901380442
Address:Vake Garden New Town New Yi Bai Road Beichen District Tianjin,China
Doi:10.1016/j.bmc.2008.07.050
(2008)Doi:10.1039/c39840000486
(1984)Doi:10.1039/b517847a
(2006)Doi:10.1016/j.jfluchem.2006.05.018
(2006)Doi:10.1246/bcsj.60.1415
(1987)Doi:10.1016/j.tet.2020.131646
(2020)