Diterpenoid compounds isolated from Salvia majdae (Rech.f. & Wendelbo) Sytsma show antiproliferative and apoptosis inducing capacity against cancer cells

Salvia majdae (Rech.f. & Wendelbo) Sytsma (Lamiaceae) is a monotypic species endemic to southern Iran. The ethanol extract of its dried roots was fractionated with n-hexane, yielding salvipisone (4) and a mixture of β-sitosterol (8) with stigmasterol (9) for the first time from this plant. Previously reported metabolites, including zhumerianone C (1), aethiopinone (2), lanugone Q (3), 11,14-dihydroxy-8,11,13-abietatrien-7-one (5), sugiol (6), and manool (7), were also isolated. Cytotoxic activity, cell cycle alterations, and apoptosis induction were evaluated against HT-29, AsPC-1, and K562 cells. Ortho-quinones zhumerianone C and aethiopinone exhibited potent cytotoxicity (IC50 = 0.9–6.8 µM), inducing S-phase arrest and apoptosis in AsPC-1 cells, while salvipisone (para-quinone) displayed the weakest effect. In silico analyses supported these findings, showing strong affinity of zhumerianone C and aethiopinone towards topoisomerase IIα. This study also resulted in the structural revision of 12,16-dideoxy-11,14-dihydroxyaegyptinone B, establishing its correct chemical structure.