Cytotoxic Labdane-type Diterpenes and Diterpene Derivative from Hedychium villosum

Abstract

Research on active components from rhizomes of Hedychium genus has led to isolation of some diterpenes with significant cytotoxic activities against Chinese hamster V-79 cells, KB cells, K562 cells, A549 cells, etc.. Hedychium villosum Wall. is a perennial rhizomatous herb distributed in China and partially in Southeast Asia, which is used in the treatment of pain and inflammation. A new labdane-type diterpene(1), together with a known one(3), were isolated from Hedychiurn villosum. The new diterpene was named as villosumcoronarin, which partially isomerized to its epimer 1' in solution, e. g., chloroform or methanol. The gross structures of compounds 1 and 1' were elucidated on the basis of MS, ER, H-1 NMR, C-13-DEPT NMR, H-1-H-1 COSY and HMBC. The relative configuration was determined by H-1 NMR, ROESY and computational methods. Compound 1 was identified as (11S, 15R)-11-hydroxy-8(17), 12(E)-labdadien-15,16-dial 11,15-hemiacetal. The known compound 3 was oxidized by Jones reagent to get diterpene derivative 4. Bioassays revealed that compound 1 had strong cytotoxic activity against HL-60 and SMMC-7721 cells with IC50 values of 0.74 and 4.48 mu mol/L, respectively, the activities were stronger than the positive control, cis-diaminedichloroplatinum(DDP). Compound 4 also showed significant activities against HL-60 and SMMC-7721 cells with IC50 values of 3.15 and 9.57 mmol/L, respectively.