Cytotoxic 4'-aminochalcones and related compounds.
A series of 4'-aminochalcones 1 and related maleamic acids 2 and Schiff bases 3 were designed and synthesized as candidate cytotoxic agents. The atomic charges on different atoms of representative compounds were calculated. Evaluation of the enones 1-3 against human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells revealed that approximately 40% of the IC50 values generated were less than 10 microM. In some cases cytotoxicity was correlated with the Hammett sigma values of the aryl substituents and less frequently with the aryl Hansch pi values. Evidence was obtained that in general these compounds displayed selective toxicity for certain malignant cells and were well tolerated in mice. This study has revealed various directions whereby the project may be amplified in the future with a view to finding compounds with increased cytotoxicity to tumour cells.
College of Pharmacy and Nutrition, University of Saskatchewan, 110, Science Place, Saskatoon SK S7N 5C9, Canada.
J R
JR
Dimmock
A
A
Jha
G A
GA
Zello
T M
TM
Allen
C L
CL
Santos
J
J
Balzarini
E
E
De Clercq
E K
EK
Manavathu
J P
JP
Stables
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D014407:Tumor Cells, Cultured
D000927:Anticonvulsants; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D002599:Chalcone