Nicotabacins A–P, New Cembrane-Type Diterpenes Isolated from Nicotiana tabacum L. and Their Antifungal Activities

Abstract

Sixteen previously undescribed cembrane-type diterpenoids, named nicotabacins A–P (1–16), were isolated from Nicotiana tabacum L., together with 12 known analogs (17–28). The structures of 1–16 were determined by extensive spectral analysis, single-crystal X-ray diffraction analysis, and ECD calculations. Compound 1 was a rare 4,5-seco-cembrane-type diterpene with 4,6-diketone and 8,11-oxygen-bridge moieties. Compounds 1–2, 4–11, 13–15, and 17–28 were evaluated for antifungal activities against Candida albicans (C. albicans), both alone and in combination with fluconazole (FLC). These compounds alone indicated no inhibitory activity against either the sensitive strain SC 5314 or the resistant strain ATCC 14053 of C. albicans. In contrast, compounds 10, 13, and 14, when combined with FLC, demonstrated a strong inhibitory effect on C. albicans resistant strain, with fractional inhibitory concentration index (FICI) values of 0.02 ± 0.01, 0.03 ± 0.01, and 0.03 ± 0.02, respectively, indicating a strong synergistic effect.