Design, synthesis, and biological evaluation of novel T-Type calcium channel antagonists.
This paper describes the synthesis of several novel T-type calcium channel antagonists that inhibit calcium influx into the cell, which in turn regulates unknown aspects of the cell cycle pathway that are responsible for cellular proliferation. A library of compounds was synthesized and a brief structure activity relationship will be described. From these studies we have identified a compound (1) that displays anti-proliferative activity in the low micromolar range across a variety of cancer cell lines.
McCalmont
William F
WF
Department of Chemistry, University of Virginia, Charlottesville, VA 22904-4319, USA. wfm3s@virginia.edu
Heady
Tiffany N
TN
Patterson
Jaclyn R
JR
Lindenmuth
Michael A
MA
Haverstick
Doris M
DM
Gray
Lloyd S
LS
Macdonald
Timothy L
TL
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D015764:Bepridil / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D015195:Drug Design; D005069:Evaluation Studies as Topic; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D010480:Perhexiline / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D015764:Bepridil; D010480:Perhexiline