ObjectiveTo study isomalabaricane triterpenes with anti-tumor activities from the marine sponge Stelletta tenuis Lindgren.MethodsA combination of multi-chromatography as well as spectral analysis were employed for the separation and determination of the compounds from the sponge (especially the quantum mechanical calculation of the electronic circular dichroic (ECD) spectrum was used to determine the absolute configurations of the new triterpenes).The cytotoxicities against human tumor cells were determined using the MTT assay.Results Fifteen compounds (1-15), including twelve isomalabaricane rriterpenes and isomalabaricane-derived natural products (1-7, 11-15), two α-pyrones (9,10) and one sterol (8) were obtained and elucidated from the genus for the first time (expect 1-4 and 8),among which five are new compounds (11-15) and one is new natural compound (10).The twelve tested triterpenes showed in vitro cytotoxicity against three human cancer cell lines A549, AGS and U-251MG.Conclusions The five new compounds all displayed novel structural characteristics.The novelty in the strucrure of 11 lied in the presence of a free β hydroxyl goup at C-13 and the saturated C-13-C-14 bond,which have never been found in isomalabaricane-type triterpenes before.The polyene side chains of isomalabaricane triterpenes were all highly conjugated and contained no more than one saturated carbon(excluding the methyl carbon), except several triterpenes recently isolated from marine sponge Rhabdastrella globostellata.11-13 were the second example of the isomalabaricanes with more than one saturated carbon in their side chains and firstly isolated from genus Stelletta.14 and 15 possessed a rarely skeleton, which only had been synthesized by researcher in 1981 and was reported here as new natural products for the first time.The new naturally α-pyrone 10 had been reported as synthetic compounds from gibepyrone B, which was isolated from the microorganism Gibberellafujikuroi (IMI:58289).This offered a possibility that the bioactive secondary metabolites from marine sponge may be produced by its associated microorganism.The preliminary structure-activity relationship of the triterpenes was also discussed.Our studies focused on triterpenes with anti-tumor activities of S.tenuis have provided valuable leads for pursuing new anti-tumor drugs, and established a homebase for further developmentof the title marine sponge with abundant resources in South China Sea.