Multitargeted Caffeic Acid Derivatives Inhibit Cardiac RyR2- and Na_V1.5- Channels but Stimulate SERCA2a Pump Activity.

ABSTRACT: Heart beat relies on coordinated calcium regulation through RyR2 and SERCA2a activity, as well as impulse propagation mediated by Na_V1.5 activity. Here, we present small molecules combining a 1,4-benzothia- or 1,4-benzoxazepine scaffold and a 3-(3,4-dihydroxyphenyl)-2-propenoic acid residue of which five compounds (4, 9, 10, 12, and 13) reduced cardiac RyR2 activity and stimulated SERCA2a activity in our cell systems. The acceleration of SERCA2 activity was particularly enhanced by cyanoborane derivatives 11-13. The substantial impact on SERCA2 activation relates to the presence of polar (zwitterionic) N-B fragments, which can increase the binding affinity to SERCA2 and result in a more efficient activation. Compounds 12 an

SUBMITTER: Mitronova GY 

PROVIDER: S-EPMC12489660 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature