Comparative Volatile Profiles and Biological Activities of Methanol and Ethyl Acetate Extracts of Two Endemic Origanum Species from Türkiye

Origanum saccatum P.H. Davis and O. solymicum P.H. Davis are two endemic species of section Amaracus distributed in Türkiye and characterized by close morphological and genetic relationships. Although their volatile and non-volatile compounds and several biological activities have previously been investigated, the antimicrobial and cytotoxic activities of methanol and ethyl acetate extracts of both species have not been systematically compared within a common experimental framework. In this study, the volatile profiles of the two species were compared, while the antimicrobial and cytotoxic activities of their methanol and ethyl acetate extracts were evaluated comparatively. Essential oils were obtained by hydrodistillation and analyzed by GC-FID/GC-MS. Antimicrobial activity was determined by the broth microdilution method, and cytotoxicity was evaluated against A549, MCF-7, and NIH/3T3 cells using the MTT assay. Both essential oils showed a p-cymene-rich profile, although substantial differences were observed in the proportions of γ-terpinene (3.1–24.4%), thymol (4.0–18.2%), borneol (0.6–15.6%), linalool (0.1–10.4%), and carvacrol (0.1–3.4%). The ethyl acetate extracts showed generally lower MIC values (125–250 µg/mL) than the corresponding methanol extracts (500–1000 µg/mL) against the most responsive microorganisms. Ethyl acetate extracts also showed the strongest cytotoxic activity with IC50 values of 6.74–14.49 µg/mL, although the response varied depending on species and cell line. The O. saccatum ethyl acetate extract showed the highest selectivity toward MCF-7 among the tested extracts, with a selectivity index of 3.176. To the best of our knowledge, this is the first report of the cytotoxicity of these two species against A549 and MCF-7 cells. The findings provide a comparative assessment of their volatile profiles and solvent-dependent biological properties.