Synthesis and properties of some novel anti-calmodulin drugs.
The preparation and properties of some novel inhibitors of calmodulin function are described. The compounds are cationic derivatives of phenyl-substituted thiazoles which inhibit the calmodulin stimulation of cyclic-AMP phosphodiesterase and are active against animal tumor cells in culture. These derivatives form the basis for the preparation of new, more potent inhibitors of calmodulin function which could take advantage of the reported elevated levels of calcium-bound calmodulin in tumor cells and show preferential anti-tumor activity.
Sakai
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TT
Comprehensive Cancer Center, University of Alabama at Birmingham 35294-2041, USA. ted@mozart.nmrcore.uab.edu
Krishna
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NR
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D011485:Protein Binding; D013844:Thiazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002147:Calmodulin; D013844:Thiazoles; D015105:3',5'-Cyclic-AMP Phosphodiesterases