ORIGINAL ARTICLE Identification of bioactive metabolites against adenosine A1 receptor using NMR-based metabolomics Kashif Ali • Muzamal Iqbal • Nancy Dewi Yuliana • Yeon-Ju Lee • Seungil Park • Saem Han • Jeong-Woo Lee • Hyi-Seung Lee • Robert Verpoorte • Young Hae Choi Received: 15 October 2012 / Accepted: 16 January 2013 / Published online: 26 January 2013 Ó Springer Science+Business Media New York 2013 Abstract Marine sponges are relatively less explored for their chemical features but highly anticipated resource for bioactive compounds. In this paper we report the screening of marine sponges crude extracts for their potential to bind the adenosine A1 receptor. Many samples showed very promising activity and in order to identify the active components, a metabolomics-chemometrics approach is employed. Nuclear magnetic resonance spectroscopy is used for the metabolic profiling of the marine sponges and partial least squares (PLS) and orthogonal PLS (OPLS) algorithms are used to correlate the metabolomics with bioactivity data. Using several two dimensional-NMR techniques, the resonances responsible for the separation of high activity samples from the medium and low activity samples were identified as associated to metabolites like halisulfate 1, halisulfate 3–5, and suvanine (1–5), all belongs to sesterterpenes class. The reference compounds for these metabolites are also tested for the activity, which endorse the findings of the applied methodology. Keywords Marine sponges Á Halisulfates Á Suvanine Á Adenosine A1 receptor binding Á NMR spectroscopy Á Chemometrics 1 Introduction Natural products, chemical compound or substance pro- duced by a living organism, are known to have a key role as resource to supply the candidates of drugs. Terrestrial organisms are considered as the primary source of such products as a number of useful natural products are origi- nated from plants (Harborne 2001). However, considering the fact that almost 75 % of the Earth’s surface is covered with water, less significant attention has been paid towards marine natural products research. Natural products from marine sources are gaining much attention now and among them sponge metabolites acquired a unique place due to the great diversity in structures, biosynthetic pathways, and bioactivities. In the area of drug research, numerous new biologically active compounds have been identified in sponge; possess anti-inflammatory, anti-tumor, immuno- suppressive, anti-viral, anti-malarial, and/or antibiotic activities (Sipkema et al. 2005). High-throughput screening of compounds, in combina- tion with high-throughput synthesis and combinatorial chemistry, for the development of a drug fails to meet the expectations as no dramatic increase in the number of lead compounds is observed in the recent past (Yuliana et al. Electronic supplementary material The online version of this article (doi:10.1007/s11306-013-0498-9) contains supplementary material, which is available to authorized users. K. Ali (&) Á M. Iqbal Á N. D. Yuliana Á R. Verpoorte Á Y. H. Choi Natural Products Laboratory, Institute of Biology, Leiden University, 2300 RA Leiden, The Netherlands e-mail: kashifali.81@gmail.com K. Ali Department of Biosciences, Shaheed Zulfikar Ali Bhutto Institute of Science & Technology (SZABIST), Karachi 75600, Pakistan N. D. Yuliana Division of Food Chemistry, Department of Food Science and Technology, Bogor Agricultural University, IPB Dramaga Campus, Bogor 16002, Indonesia Y.-J. Lee Á S. Park Á S. Han Á J.-W. Lee Á H.-S. Lee Marine Natural Product Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan 426-744, Republic of Korea 123 Metabolomics (2013) 9:778–785 DOI 10.1007/s11306-013-0498-9