Macrosphelide A (CAS: 172923-77-2)

Macrosphelide A is a 16-membered macrolide natural product originally identified as an inhibitor of cell-cell adhesion between HL-60 leukemia cells and LPS-activated endothelial cells (IC50 = 3.5 µM). It lacks significant cytocidal or broad antimicrobial activity at high concentrations, indicating a selective biological mode of action. More recent mechanistic studies revealed that macrosphelide A exerts anticancer effects by simultaneously targeting key metabolic enzymes involved in the Warburg effect, including enolase 1 (ENO1), aldolase A (ALDOA), and fumarate hydratase (FH). Direct inhibition of ENO1 enzymatic activity was experimentally confirmed. In cancer cells, treatment reduces glucose consumption, lactate production, and proliferation, and induces apoptosis. Thus, macrosphelide A functions both as a cell-adhesion modulator and a multitarget metabolic inhibitor with antitumor potential.