¹Master Program in Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia
²Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia
³Center for Natural Product Medicine Research and Development, Institute of Tropical Diseases, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia
⁴Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, Thailand DOI : 10.29228/jrp.126 The marine sponges with their unique and wide range of biodiversity, producing unusual metabolites emerge as a good candidate for new therapeutic agents, including as acetylcholinesterase (AChE) inhibitor. The aims of this study are to evaluate the potency of fractions and isolated compound from Agelas nakamurai as AChE inhibitor, as well as to determine the structure of the isolated compound. The bioassay-guided isolation protocol was carried out in this study. The AChE inhibitory assay was carried out based on the modified Ellman’s method. The structure of the isolated compound was determined by NMR spectroscopy and mass spectrometry. A diterpene alkaloid was isolated from the active fraction of A. nakamurai. This compound exhibited a molecular ion at m/z 422.3280 [M]+ in mass spectrometry. The UV profile of the isolated compound showed a strong peak at 269 nm, and the specific rotation value is [α]20D +28,0 (MeOH, c 0.25). These data together with the 1H and 13C NMR spectroscopy data are similar to that reported for iso-agelasine C. The isolated iso-agelasine C gave moderate inhibition against AChE enzyme with an IC50 value of 30.68 ± 0.92 μg/mL, which was lower compared to the extract and fractions. The stronger AChE inhibitory activity in the extract and fractions is possibly due to the synergistic activity of compounds present in the extract and fractions of A. nakamurai. Iso-agelasine C could serve as a lead for the development of diterpene alkaloid as an AChE inhibitor. Keywords : Alzheimer’s disease; acetylcholinesterase inhibitor; marine sponge; Agelas nakamurai; iso-agelasine C.