TY - JOUR
T1 - Synthesis of 5H-pyrido[3,2-b]pyrrolizin-5-one tripentone analogs with antitumor activity
AU - Cirrincione, Girolamo
AU - Parrino, Barbara
AU - Tesoriere, Luisa
AU - Attanzio, Alessandro
AU - Montalbano, Alessandra
AU - Carbone, Anna
AU - Diana, Patrizia
AU - Cascioferro, Stella Maria
AU - Barraja, Paola
AU - Spano', Virginia
AU - Ullo, Salviana
PY - 2018
Y1 - 2018
N2 - Pyrrolizinones represent an interesting class of compounds with varied degrees of structural complexity and pharmacological activity. Among these, 9H-pyrido[2,3-b]pyrrolizin-9-one, tripentone analogs, recently reported by us, showed significant antiproliferative activity against human tumor cell lines, inducing apoptosis and not affecting viability of Caco-2 differentiated in normal intestinal-like cells. Considering their interesting biological activity, their 5H-pyrido[3,2-b]pyrrolizin-5-one analogs were efficiently synthesized in good to excellent yields (61–91%). All tripentone derivatives were tested to assess their cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivatives, with IC50ranging from 0.11 to 16.11 μM, did not affect viability of Caco-2 differentiated in normal intestinal-like cells, suggesting tumor cells as the main target of their cytotoxic action. The same compounds, further investigated, showed that they did not exert necrotic effects, while induced a clear shift of viable cells towards early apoptosis confining the cells in the mitotic phases.
AB - Pyrrolizinones represent an interesting class of compounds with varied degrees of structural complexity and pharmacological activity. Among these, 9H-pyrido[2,3-b]pyrrolizin-9-one, tripentone analogs, recently reported by us, showed significant antiproliferative activity against human tumor cell lines, inducing apoptosis and not affecting viability of Caco-2 differentiated in normal intestinal-like cells. Considering their interesting biological activity, their 5H-pyrido[3,2-b]pyrrolizin-5-one analogs were efficiently synthesized in good to excellent yields (61–91%). All tripentone derivatives were tested to assess their cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivatives, with IC50ranging from 0.11 to 16.11 μM, did not affect viability of Caco-2 differentiated in normal intestinal-like cells, suggesting tumor cells as the main target of their cytotoxic action. The same compounds, further investigated, showed that they did not exert necrotic effects, while induced a clear shift of viable cells towards early apoptosis confining the cells in the mitotic phases.
KW - 2-b]pyrrolizin-5-ones; Antiproliferative activity; Antitumor; Apoptosis; Tripentones; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry
KW - 5H-pyrido[3
KW - 2-b]pyrrolizin-5-ones; Antiproliferative activity; Antitumor; Apoptosis; Tripentones; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry
KW - 5H-pyrido[3
UR - http://hdl.handle.net/10447/298797
M3 - Article
VL - 158
SP - 236
EP - 246
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -