Synthesis and biological evaluation of mono- and bis-[(alkylamino)alkylamino] substituted thienopyridopyridazines, a new class of potential antitumor agents.
A new class of potential antitumor agents, provided with thieno[2',3':5,6]pyrido[2,3-d]pyridazin-9(4H)-one nucleus as chromophore, was synthesized. Thus, the suitable amines were reacted, in different conditions, with 5,8-dichlorothieno[2',3':5,6]pyrido[2,3- d]pyridazin-9(4H)-one (5) to afford the 8-alkylamino derivatives 6a-f, the 5-alkylamino derivatives 7a-f, and the 5,8-bis-alkylamino derivatives 8a,b. Selected compounds were evaluated for cytotoxic potency in vitro against the human colon adenocarcinoma HT 29 cell line and studied in DNA binding assays. The cytotoxic potency versus HT29 was also correlated with binding affinity for calf thymus DNA.
Antonini
I
I
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Cola
D
D
Polucci
P
P
Palmieri
G F
GF
Martelli
S
S
Jenkins
T C
TC
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006358:Hot Temperature; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008942:Mitoxantrone / Q000378:metabolism / Q000494:pharmacology; D009691:Nucleic Acid Denaturation; D011485:Protein Binding; D011724:Pyridazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011724:Pyridazines; D011728:Pyridones; D004317:Doxorubicin; D004247:DNA; D008942:Mitoxantrone