d-chiro-Inositol Derivatives with Multidrug Resistance Reversal Activities from the Fruits of Chisocheton siamensis

Abstract

Chisosiamols A−K (1−11), 11 new D-chiro-inositol derivatives, along with a known analogue (12) were isolated from the fruits of Chisocheton siamensis. Their planar structures and relative configurations were elucidated by the comprehensive application of spectroscopic methods, especially from the characteristic coupling constants, and 1 H− 1 H COSY spectra. The absolute configurations of the D-chiro-inositol core were determined using the ECD exciton chirality and X-ray diffraction crystallographic analytical methods. This is the first crystallographic data reported for the D-chiro-inositol derivatives. A structural elucidation strategy mainly combining 1 H− 1 H COSY correlations and ECD exciton chirality for determining the structure of D-chiro-inositol derivatives was developed, which also led to the revisions of previously reported structures. Bioactivity evaluation indicated that chisosiamols A, B, and J can reverse multidrug resistance in MCF-7/DOX cells in the IC 50 range of 3.4−6.5 μM (RF: 3.6−7.0).