Cytotoxic and Protein Kinase Inhibiting Nakijiquinones and Nakijiquinols from the Sponge Dactylospongia metachromia

Abstract

Chemical investigation of the sponge Dactylospongia metachromia afforded five new sesquiterpene aminoquinones (1-5), two new sesquiterpene benzoxazoles (6 and 7), the known analogue 18-hydroxy-5-epi-hyrtiophenol (8), and a known glycerolipid. The structures of all compounds were unambiguously elucidated by one- and two-dimensional NMR and by MS analyses, as well as by comparison with the literature. Compounds 1-5 showed potent cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values ranging from 1.1 to 3.7 μM. When tested in vitro for their inhibitory potential against 16 different protein kinases, compounds 5, 6, and 8 exhibited the strongest inhibitory activity against ALK, FAK, IGF1-R, SRC, VEGF-R2, Aurora-B, MET wt, and NEK6 kinases (IC50 0.97-8.62 μM).

Marine natural products

“…Merosesquiterpenoids 899-930 came from the sponge genera Aka (Siphonodictyon), Dysidea, Dactylospongia and Xestosopngia. [578][579][580][581][582][583][584] In particular, xestolactone A 931 and xestosaprol O 932 were isolated from Xestospongia vansoesti (Palawan Is., Philippines). Xestosaprol O is twenty times more potent as an inhibitor of indoleamine 2,3dioxygenase (IDO; IC 50 ¼ 4 mM) than 931 (IC 50 ¼ 81 mM), making it a lead towards inhibitors of tumour immune escape.…”

An Unprecedented Blue Chromophore Found in Nature using a “Chemistry First” and Molecular Networking Approach: Discovery of Dactylocyanines A–H

“…Detailed analysis of 1 D and 2 D NMR data suggested that 9 possessed the same terpenoid quinone moiety (C‐1 to C‐21) as that of 4 as well as the presence of characteristic signals corresponding to the above mentioned 3‐(methylsulfinyl)propan‐1‐amine spin system. Furthermore, the 13 C NMR spectrum showed characteristic resonances corresponding to a phenethylamine unit . Observed HMBC correlation from H 2 ‐22 to C‐18 established the location of the 3‐(methylsulfinyl)propan‐1‐amine residue at C‐18.…”

Anticancer Drugs and Potential Anticancer Leads Inspired by Natural Products

“…A derivative of oleanolic acid triterpene, namely, 3,21-dioxo-olean-18-en-oic acid (126) (Fig. Recently, additional natural nakijiquinone derivatives with potent protein kinase inhibitory activity were isolated from a marine sponge, Dactylospongia metachromia [227]. The triterpene 126 was an inhibitor of tyrosine kinase (Tie2 kinase) with the IC 50 value of 4.2 mM; however, it showed only modest cytotoxic activity against cultured mammalian cells [216].…”

“…Many plants Reversible inhibitor and suppression of VEGFR-2 [197][198][199] Hematoxylin (118) Inhibiting Her-2/neu kinase, EGFR, and VEGFR-2; however, detailed mechanism of action has not yet been reported [224][225][226][227] activity could therefore lead to the growth inhibition of cancer cells, and it is a potential approach for cancer therapy [248].…”