BISAMIDES FROM AGLAIA SPECIES - STRUCTURE-ANALYSIS AND POTENTIAL TO REVERSE DRUG-RESISTANCE WITH CULTURED-CELLS

The structure of pyramidatine [1], a new bisamide alkaloid from leaves of Aglaia pyramidata, was determined through extensive nmr studies, including homonuclear COSY, NOESY, APT, HETCOR, and selective INEPT techniques. Revision of the C-13-nmr assignment of piriferine 12), an alkaloid previously isolated from A. pirifera, was achieved by examination of several 2D nmr spectra (homonuclear COSY, NOESY, and HETCOR) and confirmed by selective INEPT nmr experiments. Evaluation of the cytotoxic potential of the two alkaloids, along with two other bisamides from Aglaia odorata, odorine [3) and 5'-epi-odorine [4], was carried out in eleven human cancer cell lines. None of these bisamides showed significant cytotoxicity. Nevertheless, piriferine [2], odorine [3], and 5'-epi-odorine [4) were found to inhibit the growth of the vinblastine-resistant KB cells by enhancing the anticancer activity of vinblastine.