Synthesis and biological activities of ACYL derivatives of hydroxylated eudesmanolides

This research focused on the synthesis of two hydroxylated eudesmanolides, reynosin (RNS, 2) and santamarine (STM, 3) from costunolide (1) isolated from Saussurea lappa roots, and the synthesis of their acyl derivatives to study on their biological activities. A total of 20 acyl derivatives of hydroxylated eudesmanolides, including 14 new compounds: 2(a-c), 3b, 3c, 3e, 3f, 3(h-j), and 3(l-o). The compounds were then evaluated for their anti-melanogenic, anti-colorectal cancer, and anti-inflammatory activities. It was observed that STM (3) exhibited anti-melanogenic and anti-colorectal cancer activity with IC50 values of 8.02 and 15.55 µM, respectively, which was greater than RNS (2) (IC50 = 10.63 and 18.17 µM). In contrast, anti-inflammatory activity of RNS (2) was better than STM (3). Among synthesized compounds, the benzoyl derivatives displayed greater in all bioactivities assayed. Compound 3f, a para-trifluoromethylbenzoyl derivative, showed the most potent for all assays, anti-melanogenic, anti-colorectal cancer, and anti-inflammatory activities with IC50 values of 1.34, 4.41, and 3.79 µM, respectively. Moreover, compound 3e, a para-nitrobenzoyl derivative, was the second most potent for anti-melanogenic activity with an IC50 value of 2.53 µM. Both did not show significant cytotoxicity. The SAR study revealed the fluorine atom containing benzoyl moieties were required for their biological activities. This research provided information of compounds which might be developed as a useful drug/cosmetic in industry.