Aaptamine-new selective inhibitor of type a monoamine oxidases

Ioffina, D. I.; Volkovitskaya, O. É.; Gorkin, V. Z.; Rebachuk, N. M.; Utkina, N. K.; Федореев, С. А.

doi:10.1007/bf00764989

Cited by 9 publications

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“…Several types of activity are known for them including α-adrenoblocking [18], anti-HIV-1 [19], antimicrobial [19], antiherpetic [20], inhibition of monoamine oxidase A [21], inhibition of sortase A [22], and anticancer [19,23]. The mechanism of the antioxidant activity of 1 and 2 was studied for the first time although antioxidant activity had been observed for 1 and 2 previously [7].…”

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Antioxidant activityofaromatic alkaloids from the marine sponges Aaptos aaptos and Hyrtios SP.

Utkina

2009

Chem Nat Compd

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547.94+593.4Aaptamine (1) and isoaaptamine (2) were isolated from the marine sponge Aaptos aaptos; 6-bromo- 2′-de-N-methylaplysinopsin (3) from the marine sponge Hyrtios sp. Alkaloids 1-3 were tested for the ability to trap 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, to reduce Folin-Ciocalteau reagent (FCR), and to inhibit oxidation of linoleic acid (LA) induced by peroxide radicals. Compounds 1 (IC 50 18 μM), 2 (IC 50 16 μM), and 3 (IC 50 18 μM) reacted strongly with DPPH, comparable with trolox (IC 50 16 μM) and showed high reducing ability for FCR. The inhibition of LA oxidation by 1-3 was comparable with that of ionol (BHT). It was shown that the antioxidant activity of 1-3 was related to their ability to release both electrons and H atoms.Research on marine natural compounds, which began about 60 years ago, has shown that almost every class of marine organisms synthesizes a variety of molecules with unique structures that are not observed among natural compounds from terrestrial sources owing to the physical and chemical conditions of the marine environment [1,2]. Marine sponges are one of the most ancient classes of animals. The class Demospongiae contains about 95% of living species and is represented around the world by about 14,000-15,000 species [3]. Marine sponges, from which more than 50% of marine natural compounds have been isolated [2], are a rich source of compounds with cytotoxic and antitumor properties [4,5]. The antioxidant activity of compounds isolated from marine sponges is relatively little studied [6-9]. Avarol from the Mediterrean sponge Disydea avara is the only example of a well studied antioxidant from sponges. It is currently manufactured as a preparation against psoriasis [10].In continuation of the search for antioxidants from marine organisms, we investigated marine sponges Aaptos aaptos (Hadromerida, Suberitidae) and Hyrtios sp. (Dictyoceratida, Thorectidae), the alcohol extracts of which acted as strong traps for 2,2-diphenyl-1-picrylhydrazyl radical (DPPH). Our goal was to isolate the active metabolites from these species of marine sponges and study the antioxidant activity and mechanism of antioxidant activity of the obtained compounds.Fractionation of the extract from A. aaptos isolated compounds that were active traps for DPPH. These were aaptamine (1), isoaaptamine (2), and their HCl salts. They were identified by comparison of their spectral properties with the literature [11,12]. Fractionation of the extract from Hyrtios sp. isolated the active compound 6-bromo-2′-de-N-methylaplysinopsin (3), which was identified by comparison of spectral data with those published [13].

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Antioxidant activityofaromatic alkaloids from the marine sponges Aaptos aaptos and Hyrtios SP.

Utkina

2009

Chem Nat Compd

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“…In addition, it was observed that the deamination of benzylamine, the specific substrate of MAO-B, either was not completely blocked or it was inhibited to a minor degree in comparison with the oxidative deamination of serotonin, the specific substrate of MAO-A. 149 Aaptamine was also found to be an inhibitor of glutamine: fructose-6-phosphate amidotransferase (GFAT) during a high throughput screening program searching for enzymatic inhibitors in natural products' extracts (IC 50 ¼120 mM). 36 GFAT is an attractive target for the discovery of drugs, which may be used for the treatment of type II diabetes.…”

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Aaptamine and related products. Their isolation, chemical syntheses, and biological activity

2009

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“…Aaptamine’s potential for drug development is further evidenced by the actual results of a highly diverse group of molecular targets already evaluated. In addition to antiviral (5,17) and anticancer (4,6,18) activities, the aaptamines have a strong in vitro radical scavenging capacity (19) and have been shown to block α‐adrenoceptor action (1) as well as inhibit α‐1,3‐glucanase (20) and monoamine oxidase (21). Still, compounds which are active against a variety of targets are certain to encounter problems with indiscriminant toxicities.…”

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“…Each product was evaluated for activity in a variety of whole cell and viral assays including a unique solid tumor disk diffusion assay. Details of aaptamine's DNA-binding activity ceptor action (1) as well as inhibit a-1,3-glucanase (20) and monoamine oxidase (21). Still, compounds which are active against a variety of targets are certain to encounter problems with indiscriminant toxicities.…”

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Antiviral and Anticancer Optimization Studies of the DNA‐binding Marine Natural Product Aaptamine

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Aaptamine has potent cytotoxicity that may be explained by its ability to intercalate DNA. Aaptamine was evaluated for its ability to bind to DNA to validate DNA binding as the primary mechanism of cytotoxicity. Based on UV-vis absorbance titration data, the K(obs) for aaptamine was 4.0 (+/-0.2) x 10(3) which was essentially equivalent to the known DNA intercalator N-[2-(diethylamino)ethyl]-9-aminoacridine-4-carboxamide. Semi-synthetic core modifications were performed to improve the general structural diversity of known aaptamine analogs and vary its absorption characteristics. Overall, 26 aaptamine derivatives were synthesized which consisted of a simple homologous range of mono and di-N-alkylations as well as some 9-O-sulfonylation and bis-O-isoaaptamine dimer products. Each product was evaluated for activity in a variety of whole cell and viral assays including a unique solid tumor disk diffusion assay. Details of aaptamine's DNA-binding activity and its derivatives' whole cell and viral assay results are discussed.

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Aaptamine-new selective inhibitor of type a monoamine oxidases

Cited by 9 publications

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Antioxidant activityofaromatic alkaloids from the marine sponges Aaptos aaptos and Hyrtios SP.

Antioxidant activityofaromatic alkaloids from the marine sponges Aaptos aaptos and Hyrtios SP.

Aaptamine and related products. Their isolation, chemical syntheses, and biological activity

Antiviral and Anticancer Optimization Studies of the DNA‐binding Marine Natural Product Aaptamine

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