A joint molecular networking study of a Smenospongia sponge and a cyanobacterial bloom revealed new antiproliferative chlorinated polyketides

Abstract

Feature based molecular networking was used to compare chlorinated metabolites of S. aurea and Trichodesmium sp. and revealed four new antiproliferative polyketides.

Fast Detection of Two Smenamide Family-Members Using Molecular Networking

“…Cluster 1, containing smenamide A and B, along with smenamide C and two minor unidentified compounds; cluster 2, containing smenamide E and three more compounds, two of which were identified as smenamides F and G. the E conformer showed a correlation peak between H3-26 (δ 2.11) and H2-24 (δ 3.39) ( Figure 3). As discussed in our previous work [6], for such a system, only two low-energy conformers may exist ( Figure 4A), because of the unfavorable syn-pentane interactions [20] present in all the other conformers. In addition, for this system, the expected pattern of couplings between vicinal protons is opposite between the two conformers ( Figure 4A).…”

“…To further our understanding of the activity-related structural features of this class of molecules, a series of short derivatives of the 16-epi-series were designed, prepared, and tested for antiproliferative activity [9]. Recently, the family of smenamide compounds has further expanded with the isolation of smenamides C, D, and E. Interestingly, smenamides C (5) and E (7) showed moderate neurotoxicity against neuro-2A cells, while smenamide D (6), the geometric isomer of 5, did not show any cytotoxic activity [10]. In this study, the use of a molecular networking dereplication strategy resulted in the rapid detection from extracts of S. aurea of two new members of the smenamide family, smenamide F (1) and G (2).…”

“…Molecular networking is a powerful bioinformatic tool used to speed up dereplication of compounds from the organic extract, leading to the identification of known metabolites as well as new analogues [12,13]. Specifically, raw LC-MS data were first pre-processed using the mzMine program [14] to deconvolute chromatographic peaks, distinguish between isomeric compounds based on their retention times, and remove isotope and adduct peaks, as described in details in our previous paper [6]. Then, the .mgf MS2 data files were submitted to the Global Natural Product Social Molecular Network (GNPS) online platform [15], along with the reference MS2 spectra of smenamides C and E [10], and a molecular network was generated.…”

“…Our research program, aimed at discovering new bioactive compounds from marine organisms, focused in recent years on the metabolome of Caribbean sponges of the genus Smenospongia, which have proven to be very rich in new chlorinated secondary metabolites. Among them there are smenamides [ 3 ], smenothiazoles [ 4 ] and conulothiazoles [ 5 ], belonging to the hybrid peptide/polyketide chlorinated class of compounds; smenolactones, four chlorinated compounds with a polyketide structure [6]; and smenopyrone, a biogenetically different compound with a polypropionate structure containing two -pyrone rings [7]. 2…”

In Vitro Antiproliferative Evaluation of Synthetic Meroterpenes Inspired by Marine Natural Products

“…Antiproliferative assays were performed by using the xCELLigence System Real-Time Cell Analyzer (ACEA Biosciences, San Diego, CA, USA), as previously described [22]. MCF-7 cells were seeded at a cell density of 3000 cells/well, BxPC-3 at a cell density of 2500 cells/well, and MG-63 cells at a cell density of 4000 cells/well.…”