A new thiodiketopiperzaine from the marine sponge Tedania sp.

Abstract A new thiodiketopiperzaine, tedanizaine A (1), together with six known ones, were isolated from the marine sponge Tedania sp. Their structures were determined by spectroscopic analyses. The absolute configuration of 1 was established by ECD calculation. Compound 1 was the second example of thiodiketopiperazine bearing a thiazolidine unit. Cytotoxic activities of 1 were also evaluated. Graphical Abstract

In the course of our search for structurally unique and biologically interesting constituents from the marine sponges, a new thiodiketopiperzaine, tedanizaine A (1), together with six known ones (2-7), have been isolated from the sponge Tedania sp. (Figure 1). Compound 1 was the second example of thiodiketopiperazine bearing a thiazolidine unit. Herein, we describe the isolation and structure elucidation of these compounds. .4]. The above spectral data were similar to those of cyclo(L-Pro-L-thioPro) (Dillman and Cardellina 1991), suggesting that 1 could be a thiodiketopiperazine. With the aid of 1 H-1 H COSY, HSQC and HMBC experiments, the 1 H and 13 C NMR signals of 1 were assigned as shown in Table S2.

Results and discussion
The 1 H-1 H COSY data of 1 revealed the presence of three spin coupling systems in bold as shown in Figure S2. In the HMBC spectrum, the correlations between H-2/H-6 and C-4, between H-2 and C-11/C-12 as well as between H-8/H-12 and C-10 verified the skeleton of thiodiketopiperzaine.
The relative stereochemistry of 1 was determined by a NOESY experiment. The correlations between H-11 and H-5/H-13 revealed that these protons were in the same orientation ( Figure S3). The quantum chemical CD calculation method was used to establish the absolute configuration of 1. The overall predicted CD spectra of (2S, 5S, 11R)-1 and (2R, 5R, 11S)-1 were subsequently compared with the experimental one ( Figure S1). The calculated CD curve of (2S, 5S, 11R)-1 revealed a good agreement with the measured one. Consequently, the absolute structure of 1 was deduced to be 2S, 5S and 11R.

Animal material
The sponge Tedania sp. were collected from Zhanjiang, Guangdong province, China, at a depth of 10 m, in August 2015, and authenticated by Dr. De-Xiang Wang (Xiamen University). The voucher was preserved at the Department of Chemistry, College of Chemistry and Materials Science, Jinan University.

Cytotoxic activity
Cytotoxic activity of 1 was evaluated against A549 and RAW 264.7 by using MTT method (Alley et al. 1988;Suzuki et al. 1997). Briefly, fresh A549 and RAW 264.7 cells (2.5 Â 10 4 cells/ml) were cultured in 96-well plates and incubated at 37 C for 12 h in a humidified atmosphere at 5% CO 2 and 95% air. The solutions of 1 were added to the wells and the plates were successively incubation for 48 h under the same conditions. Then, 20 ll of MTT was added to each well. After incubation at 37 C for 4 h, all the supernatant was removed and 100 ll of dimethyl sulfoxide (DMSO) was added to each well and incubated for another 20 min. The absorbance of each well was then measured at 570 nm using a Thermo scientific Multiskan FC multiplate photometer (Waltham, MA, USA). The IC 50 values were calculated based on the dose-response curves.

Conclusions
The sponge Tedania sp. was investigated and led to the isolation of a new thiodiketopiperzaine, tedanizaine A (1) and six known ones (2-7). Compound 1 was the second example of thiodiketopiperazine bearing a thiazolidine unit. Compounds 2, 3 and 6 were isolated from the genus Tedania for the first time. However, compound 1 showed no inhibitory activities on the growth of A549 and RAW 264.7 cell lines.

Disclosure statement
No potential conflict of interest was reported by the author(s).