Anthracene based compounds as new L-type Ca2+ channel blockers: design, synthesis, and full biological profile.
L-Type Ca(2+) channels (LTCCs) play a key role in the regulation of vascular smooth muscle contraction, and substances that interfere with their function (Ca(2+) channel blockers) are widely used in the therapy of hypertension. Here, we report anthracene-maleimide derivatives as new LTCC blockers. Among these, 3, lacking intracellular effects, was investigated in more detail. The results show that 3 binds preferentially to inactivated LTCCs, directly interacting with the pore-forming subunit of the channel.
Bova
Sergio
S
Department of Pharmacology and Anaesthesiology, University of Padova, Italy.
Saponara
Simona
S
Rampa
Angela
A
Gobbi
Silvia
S
Cima
Lorenzo
L
Fusi
Fabio
F
Sgaragli
Giampietro
G
Cavalli
Maurizio
M
de los Rios
Cristobal
C
Striessnig
Jörg
J
Bisi
Alessandra
A
D000818:Animals; D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D015195:Drug Design; D066298:In Vitro Techniques; D008301:Maleimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000502:physiology; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D013329:Structure-Activity Relationship
D000873:Anthracenes; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D008301:Maleimides; D021122:Protein Subunits