ABSTRACT
Three new isomeric corniculatolides (1, 2, and 3) with an unusual caffrane and isocorniculane framework, and five known metabolites were isolated from the chloroform extract of the stems of Xylocarpus granatum. The structures of the new metabolites were deduced as corniculatolide B (1), isocorniculatolide B (2), and corniculatolide C (3) by spectroscopic data analysis and a combination of chemical transformations and supported by single-crystal X-ray crystallographic data of 1 and 3. The isolated compounds were evaluated for their in vitro cytotoxicity and α-glucosidase (Saccharomyces cerevisiae) inhibitory potential. Compound 3 possessed α-glucosidase inhibitory activity with an IC50 value of 24.8 µM, whereas these rare macrolides showed no effect on the mammalian cancer cell lines MIAPaCa-2, DU145, MCF-7, and HTC-116.
Subject(s)
Glycoside Hydrolase Inhibitors/chemistry , Meliaceae/chemistry , Crystallography, X-Ray , Molecular StructureABSTRACT
Two new resin glycosides, ipomeolides A (1) and B (2), both with an unusual nonlinear heteropentasaccharide core, along with five known compounds were isolated from the n-hexane/CHCl3 (1:1) extract of the aerial parts of Ipomoea pes-caprae. Ipomeolides A (1) and B (2) are macrolactone analogues of the rare (11 R)-jalapinolic acid, and macrolactonization occurred at C-2 of the second saccharide moiety. Compounds 1 and 2 show structural variation even in the pentasaccharide core. The structures of 1 and 2 were established by a combination of spectroscopic techniques as well as chemical modifications such as acetyl and acetonide derivatives as well as hydrolysis products. The new glycosidic acid was named ipomeic acid (1c). Compounds 1, 1b, and 2b were evaluated for cytotoxicity against human tumor cell lines. Compounds 1b and 2b were not effective on epithelial cells, but affected survival of K-562, which is of hematopoietic origin. A sublethal concentration of compound 1 (4 µM) when used in combination with 1 µM doxorubicin, an anticancer agent, significantly enhanced cytotoxicity to tumor cells. Such combined synergistic potency against leukemia cells and the absence of effects on epithelial cells may be beneficial for chemotherapy with minimal side effects to treat CML (chronic myeloid leukemia) malignancies.
