A β-Carboline Alkaloid from the Papua New Guinea Marine Sponge Hyrtios reticulatus

Abstract

A new 1-imidazoyl-3-carboxy-6-hydroxy-β-carboline alkaloid, named hyrtiocarboline (1), was isolated from a Papua New Guinea marine sponge Hyrtios reticulatus. The structure was elucidated from spectroscopic data, including 1 H-15 N HMBC NMR experiments that provided complementary 15 N chemical shift information in support of the structure. This compound showed selective anti-proliferative activity against H522-T1 non-small cell lung, MDA-MB-435 melanoma, and U937 lymphoma cancer cell lines.Marine sponges of the genus Hyrtios (Demospongia class, Dictyoceratida order, Thorectidae family) have proven to be a rich and structurally diverse source of cytotoxic compounds as leads for new anticancer therapeutics. The list of cytotoxic compounds spanning several classes of secondary metabolites includes spongistatins1 or altohyrtins2 (macrolides), sesterstatins3 (sesterterpenes), puupehenone4 and 15-oxopuupehenol5 (mixed sesquiterpene-shikimates), and hyrtioerectines6 (tryptamine-derived alkaloids). Until now, only two reports on secondary metabolites from H. reticulatus have been published. The first report described 5-hydroxytryptamine-derived alkaloids (β-carbolines) from H. reticulatus collected in south west Sulawesi (Indonesia), 7 followed by the sesterterpene heteronemin, isolated by bioassay-guided fractionation with a farnesyl transferase inhibition assay, from H. reticulatus obtained in Vanuatu. 8 In this paper, we report the isolation of a new 3-carboxy-β-carboline alkaloid (1), which we have named hyrtiocarboline, together with the known compounds, sacrotride A (2) 9, 10 and 1-O-hexadecyl-sn-glycero-3-phosphocholine (3), 11 from the marine sponge H. reticulatus.The sponge H. reticulatus was collected and preserved according to our standard laboratory procedures, and then stored at 4 °C. 12 The preliminary extraction for bioassay and dereplication analysis was carried out using Accelerated Solvent Extraction (ASE) where approximately 100 g of sponge were extracted with the solvent series hexanes, dichloromethane, and methanol. The dichloromethane and methanol extracts were then tested for antiproliferative activity in a primary screen against U937 histiocytic lymphoma cancer cells, and the dichloromethane extract was found to be active (98.6% inhibition @ 10 μg/mL). four human cancer cell lines, including HT-29 colon cancer cells (3.8 μg/mL), H522-T1 nonsmall-cell cancer cells (8.0 μg/mL), MDA-MB-435 melanoma (0.9 μg/mL), and U937 histiocytic lymphoma cells (2.9 μg/mL). Dereplication analysis of the extract was conducted using a HPLC-UV-ELSD-MS system equipped with a C 18 HPLC column, and a binary mobile phase of acetonitrile/0.1% formic acid and water/0.1% formic acid, spanning a gradient from 10% to 100% acetonitrile over 30 min. The resulting UV-DAD and MS data for the major peaks were then cross-checked for reported structures in MarinLit. 14 Three peaks with molecular ions at m/z 323, 463 and 482 did not correspond to any reported compounds based on mass and occurrence in Hyrtios and were designat...

RhII2‐Catalyzed Synthesis of α‐, β‐, or δ‐Carbolines from Aryl Azides

“…In conclusion, we have developed a method to access a-, b-, or d-carbolinium ions from aryl azides with orthopyridinium ion substituents using 1-5 mol % of [Rh 2 (esp) 2 ]. In combination with our previous report using RuCl 3 to access g-carbolinium ions, we believe our work demonstrates that metal-catalyzed CÀH bond amination is a simple, efficient strategy to access all possible carbolinium ion isomers from readily accessible aryl azides. The synthetic utility of our method was illustrated in a four-flask synthesis of cytotoxic and antiplasmodial agent, neocryptolepine and the analgesic oxindole (AE)-horsfiline.…”

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Carbolines and tetrahydrocarbolines are common structural motifs in pharmaceuticals and natural products. [1] b-Carboline and its saturated analog, tryptoline, are particularly prevalent [2,3] and continue to inspire methods to efficiently access them. [4,5] In contrast, methods to access the d- [6] or a-isomer [7] are uncommon despite the important biological properties exhibited by these carbolines.

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Anticancer agents from marine sponges

“…Inman et al reported a novel alkaloid 1-imidazoyl-3-carboxy-6-hydroxy-b-carboline, isolated from the marine sponge collected in Papua New Guinea. Hyrtiocarboline (1) (Figure 1) exhibited antiproliferative activity against H522-T1 (nonsmall cell lung), MDA-MB-435 (melanoma), and U937 (lymphoma) tumor cell lines with IC 50 values ranging from 1.2 to 3 mg/ml [9].…”

Identification of quinoline, carboline and glycinamide compounds in cow milk using HRMS and NMR

“…Considering the raw formula of C 13 H 10 N 2 O 2 , we hypothesised a b-carboline structure for compound D. Based on the 13 C chemical shifts databases (Inman et al, 2010), the C 3 was connected to the carboxy group and assigned the chemical shift d = 129.4 ppm. Moreover, the b-carboline structure was the only solution that could explain the strong interactions between the H 1' and the C 9a atom observed on the 1 H-13 C HMBC spectrum.…”