Discovery of arjunolic acid as a novel non-zinc binding carbonic anhydrase II inhibitor

•The present study describes: A novel non-zinc binding inhibition of CA II activity by arjunolic acid (AA).•AA was the most potent in inhibiting CA II activity in vitro (IC50=9μM).•AA also inhibited the intracellular activity of CA in H9c2 cardiomyocytes.•The decreased acidification lowered the Ca2+ levels & prevented Δψm depolarization.•SAR studies show that AA H-bonds with key catalytic residues (His64, Asn62 & 67).