Marine Cyclic Guanidine Alkaloids Monanchomycalin B and Urupocidin A Act as Inhibitors of TRPV1, TRPV2 and TRPV3, but not TRPA1 Receptors

Abstract

Abstract:Marine sponges contain a variety of low-molecular-weight compounds including guanidine alkaloids possessing different biological activities. Monanchomycalin B and urupocidin A were isolated from the marine sponge Monanchora pulchra. We found that they act as inhibitors of the TRPV1, TRPV2, and TRPV3 channels, but are inactive against the TRPA1 receptor. Monanchomycalin B is the most active among all published marine alkaloids (EC 50 6.02, 2.84, and 3.25 µM for TRPV1, TRPV2, and TRPV3, correspondingly). Moreover, monanchomycalin B and urupocidin A are the first samples of marine alkaloids affecting the TRPV2 receptor. Two semi-synthetic urupocidin A derivatives were also obtained and tested against TRP (Transient Receptor Potential) receptors that allowed us to collect some data concerning the structure-activity relationship in this series of compounds. We showed that the removal of one of three side chains or double bonds in the other side chains in urupocidin A led to a decrease of the inhibitory activities. New ligands specific to the TRPV subfamily may be useful for the design of medicines as in the study of TRP channels biology.

New Insectotoxin from Tibellus Oblongus Spider Venom Presents Novel Adaptation of ICK Fold

“…All tests on expressed channels were performed according to previously described standard protocols. Testing for receptors rTRPV1, mTRPV2, hTRPV3, rTRPA1, stably expressed in CHO cells, was carried out using the calcium imaging method as described [ 64 ]. The maximal tested concentration of peptide was 1 μM.…”

Crambescidin 800, Isolated from the Marine Sponge Monanchora viridis, Induces Cell Cycle Arrest and Apoptosis in Triple-Negative Breast Cancer Cells

“…Following bioassay-guided fractionation of the most active sponge Monanchora viridis , we isolated crambescidin 800 (C800), a guanidine alkaloid, as an active compound against TNBC cells. Guanidine alkaloids from sponges of genus Monanchora are reported to have diverse chemical structures and biological activities [ 21 , 22 , 23 , 24 ], which includes inducing cytotoxic activities [ 25 , 26 ] and apoptosis against leukemia cells [ 25 , 27 ], overcoming drug resistance by induction of autophagy and lysosomal membrane permeabilisation in urogenital cancer cells [ 28 ], and inhibiting HIV-1 fusion [ 29 ], transient receptors potential channels [ 30 ], and EGF-induced neoplastic transformation in cancer cells [ 31 ]. It was also reported that the alteration of the compound’s structure affected its cytotoxic activities, inducing apoptosis, cell cycle progression, and the induction of signaling pathways in cancer cells [ 31 ].…”

Marine Pharmacology in 2016–2017: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…panicea polyacetylene isopetrosynol ( 284 ) [ 306 ]; cyanobacterium Leptolyngbya sp. macrolide polyketide leptolyngbyolide B ( 285 ) [ 307 ]; ascidian Lissoclinum mandelai macrocyclic polyketide mandelalide C ( 286 ) [ 308 ]; sponge Hyrtios digitatus tetracyclic merosesquiterpene 19-methoxy-9,15-ene-puupehenol ( 287 ) [ 309 ]; sponge Monanchora pulchra cyclic guanidine alkaloid monanchomycalin B ( 288 ) [ 310 ]; sponge Plakortis simplex polyketide monotriajaponide A ( 289 ) [ 311 ]; sponge Mycale lissochela terpenoid mycalenitrile-15 ( 290 ) [ 312 ]; sponge Hyrtios sp. meroterpenoid nakijinol G ( 291 ) [ 313 ]; sponge Theonella swinhoei cyclic pentapeptide nazumazole D ( 292 ) [ 314 ]; fungus Aspergillus sp.…”