The synthesis of new imidazo[2,1-b]thiazoles bearing phenolic groups is reported. These compounds and some previously described analogs were evaluated as antioxidant agents with three chemical model systems, and cancer chemopreventive potential was examined by inhibition of NO production, TNF-a activated NFkB activity, and aromatase activity, as well as induction of QR1 and RXRE binding. Two of the test compounds, 9 and 12, displayed promising activity by inhibiting iNOS, NFkB and aromatase in dose edependent manner, with IC50 values in low micromolar range. The same compounds activated QR1 in a bifunctional manner. When incubated with human liver microsomes, the active compounds were further hydroxylated on the parent ring system, suggesting the next logical step in the development of these promising leads will entail synthetic production of metabolites followed by additional assessment of biological activity.
Chemopreventive and antioxidant activity of 6-substituted imidazo [2,1-b]thiazoles / Aldo Andreani; Alberto Leoni; Alessandra Locatelli; Rita Morigi; Mirella Rambaldi; Rinaldo Cervellati; Emanuela Greco; Tamara P. Kondratyuk; Eun-Jung Park; Ke Huang; Richard B. van Breemen; John M. Pezzuto. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 68:(2013), pp. 412-421. [10.1016/j.ejmech.2013.07.052]
Chemopreventive and antioxidant activity of 6-substituted imidazo [2,1-b]thiazoles
ANDREANI, ALDO;LEONI, ALBERTO;LOCATELLI, ALESSANDRA;MORIGI, RITA;RAMBALDI, MIRELLA;CERVELLATI, RINALDO;GRECO, EMANUELA;
2013
Abstract
The synthesis of new imidazo[2,1-b]thiazoles bearing phenolic groups is reported. These compounds and some previously described analogs were evaluated as antioxidant agents with three chemical model systems, and cancer chemopreventive potential was examined by inhibition of NO production, TNF-a activated NFkB activity, and aromatase activity, as well as induction of QR1 and RXRE binding. Two of the test compounds, 9 and 12, displayed promising activity by inhibiting iNOS, NFkB and aromatase in dose edependent manner, with IC50 values in low micromolar range. The same compounds activated QR1 in a bifunctional manner. When incubated with human liver microsomes, the active compounds were further hydroxylated on the parent ring system, suggesting the next logical step in the development of these promising leads will entail synthetic production of metabolites followed by additional assessment of biological activity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
