Synthesis of new pyrazolo[5,1-c][1,2,4] benzotriazines, pyrazolo[5,1-c]pyrido[4,3-e][1,2,4] triazines and their open analogues as cytotoxic agents in normoxic and hypoxic conditions.
The synthesis and antitumor activity in normoxic and hypoxic conditions of a series of pyrazolo[5,1-c][1,2,4]benzotriazine and its related analogues are reported. All compounds were tested on human colorectal adenocarcinoma cell line HCT-8 and for compounds 15 and 20, which show to have selective cytotoxicity in hypoxic and in normoxic conditions respectively, ROS production, cell cycle, and DNA fragmentation were measured. This preliminary study encouraged us to consider 15 and 20 as interesting leads for further optimization.
Ciciani
Giovanna
G
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Polo Scientifico, Sesto Fiorentino, Firenze, Italy. giovanna.ciciani@unifi.it
Coronnello
Marcella
M
Guerrini
Gabriella
G
Selleri
Silvia
S
Cantore
Miriam
M
Failli
Paola
P
Mini
Enrico
E
Costanzo
Annarella
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010100:Oxygen / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D011720:Pyrazoles; D017382:Reactive Oxygen Species; D014227:Triazines; D010100:Oxygen