Ingenine F: A new cytotoxic tetrahydro carboline alkaloid from the Indonesian marine sponge Acanthostrongylophora ingens

Abstract

Background:Marine organisms are established to be a wealthy source of bioactive compounds with diverse chemical structures and bioactivities. Acanthostrongylophora ingens is known to be rich with pyrimidine b-carboline and manzamine-type alkaloids. The goal of the present work is to isolate and identify new alkaloids from A. ingens as well as to assess the cytotoxic potential of these metabolites towards various cancer cell lines.Methods:The crude MeOH extract of the sponge was separated by vacuum liquid chromatography (VLC), using n-hexane, EtOAc, and MeOH. The EtOAc fraction was chromatographed on VLC, SiO2, sephadex LH-20, and RP18 columns, affording four metabolites. Their structures were identified using infrared, ultraviolet, high-resolution mass spectrometry, and nuclear magnetic resonance spectroscopic techniques, as well as comparison with the published data.Results:A new 1,2,3,4-tetrahydro-β-carboline (THβCs) alkaloid, ingenine F (4) and three known compounds: Annomontine (1), acanthomine A (2), and 1-oxo-1,2,3,4-THβCs (3) were isolated and identified. Ingenine F (4) exhibited cytotoxic activity toward hormone-dependent breast carcinoma (MCF7), colon carcinoma (HCT116), and lung carcinoma (A549) cell lines with IC50 values of 2.82, 1.00, and 2.37 μM, respectively, compared to doxorubicin (IC50 0.012, 0.036, and 0.102 μM, respectively).Conclusion:It is the first report for the isolation of THβCs alkaloids from A. ingens. The THβCs alkaloid with N-methylbutyramide unit as found in ingenine F is very rarely encountered in nature. Ingenine F may provide new promising candidates for potential cytotoxic agent.SUMMARY Ingenine F, a new 1,2,3,4-THβCs derivative (4) and three known alkaloids (1-3) were isolated from A. ingens. Their structures were verified by various spectroscopic analyses. Compound 4 had potent cytotoxic effect toward MCF7, HCT116, and A549 cancer cell lines. Abbreviations used: 1D: One-dimensional; 2D: Two-dimensional; CC: Column chromatography; COSY: Correlations spectroscopy; DMSO: Dimethyl sulfoxide; HMBC: Heteronuclear multiple bond correlation experiment; HRESIMS: High resolution electrospray ionization mass spectrometry; HSQC: Heteronuclear single quantum correlation; IR: Infrared; LCQ: Liquid chromatography quadrupole; LTQ: Linear trap quadropole; NMR: Nuclear magnetic resonance; RP: Reversed phase; SiO2: Silica gel; TLC: Thin-layer chromatography; UV: Ultraviolet; VLC: Vacuum liquid chromatography.

Anticancer Potential of β‐Carboline Alkaloids: An Updated Mechanistic Overview

“…[45] A. ingens yielded four novel β-carboline alkaloids such as ingenine, annomontine, acanthomine A and 1,2,3,4-tetrahydronorharman-1-one, and they had cytotoxic activity. [45] Traditional herbal medicine and meals have traditionally included sacred lotus (Nelumbo nucifera…”

“…Indonesian marine sponge [45] Gaertn). [55] In numerous medical systems, including Ayurveda, Chinese traditional medicine, and Eastern medicine, all sections of N. nucifera have been employed for various medicinal purposes.…”

Synthesis and fungicidal activity of novel pyrroloindole scaffolds and their derivatives

“…[1][2][3][4] Members of this family, the pyrroloindole derivatives, have the advantages of low toxicity, easy degradation and not easily-acquired resistance. 5 Many bioactive pyrroloindole derivatives have been isolated from physostigmine, calycanthine and calycanthaceous alkaloids, etc., [6][7][8][9] and most of them have a variety of biological activities, such as antifungal, [10][11][12][13][14][15][16] anticancer, [17][18][19] antiviral, inhibition of melanogenesis 20,21 and inhibition of acetyl cholinesterase. 22 Based on a great number of investigations toward the calycanthaceous alkaloid crucial scaffold, novel bioactive lead compounds have been discovered.…”

Synthesis and Investigation of Tetrahydro-β-carboline Derivatives as Inhibitors of Plant Pathogenic Fungi

“…Naturally occurring compounds have always played an important role in drug discovery. In particular, the β-carboline based moiety represents the core structure of several pharmaceutical activities [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ], such as anticancer [ 3 , 4 , 13 ], antimicrobial [ 5 ], antimalarial [ 7 ], antiviral [ 9 ], and antifungal activities [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Many bioactive β-carboline-based compounds have been found to be important sources of drugs and drug leads, and most of them have been isolated from marine invertebrates, such as the marine sponge [ 5 , 6 , 7 , 8 , 10 , 21 , 22 , 23 ], tunicate [ 4 , 24 , 25 ], gorgonian [ 26 ] and alga [ 27 ].…”

“…For example, as shown in Figure 1 , Eudistomins and their analogs were isolated from several species of marine organisms, mainly the active Caribbean colonial tunicate, and possessed a wide range of biological activities [ 28 , 29 , 30 , 31 , 32 ]. Ingenines, β-carboline alkaloids with a saturated/unsaturated tricyclic ring system, were isolated from the Indonesian marine sponge Acanthostrongylophora ingens and exhibited promising candidates for potent cytotoxic agents [ 13 , 33 , 34 ]. 6-Chloro-9-(3-(4-chlorophenoxy)propyl)-2,3,4,9-tetrahydro-1 H -pyrido [3,4- b ]indole TFA displayed in vitro and in vivo antifungal activity of Cryptococcus neoformans by induction of cell growth at the G2 phase on the Cdc25c/CDK1/cyclin B pathway [ 18 ].…”