Bioactive Poly(Arsenic) Compounds

Mancini, Ines; Defant, Andrea

doi:10.1007/978-3-642-41004-8_7

Cited by 7 publications

(2 citation statements)

References 66 publications

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“…Significant examples include the synthetic drug salvarsan, which has been used to treat syphilis and trypanosomiasis, which is also known as the sleeping sickness, and arsenic trioxide, which has been exploited in traditional Chinese medicine for a long time. It was also approved for the treatment of acute promyelocytic leukemia by the Food and Drug Administration (FDA) in 2000 and is currently studied for the treatment of solid tumors [ 19 ]. In the context of the results obtained so far with both arsenicin A and its synthetic analogues, we expect that new related arsenicals may contribute to promising perspectives in the development of novel arsenical drugs.…”

Section: Introductionmentioning

confidence: 99%

New Sulfur-Containing Polyarsenicals from the New Caledonian Sponge Echinochalina bargibanti

et al. 2018

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Arsenicin A (C3H6As4O3) was isolated from the New Caledonian poecilosclerid sponge Echinochalina bargibanti, and described as the first natural organic polyarsenic compound. Further bioguided fractionation of the extracts of this sponge led us to isolate the first sulfur-containing organic polyarsenicals ever found in Nature. These metabolites, called arsenicin B and arsenicin C, are built on a noradamantane-type framework that is characterized by an unusual As–As bonding. Extensive NMR measurements, in combination with mass spectra, enabled the assignment of the structure for arsenicin B (C3H6As4S2) as 2. The scarcity of arsenicin C and its intrinsic chemical instability only allowed the collection of partial spectral data, which prevented the full structural definition. After the extensive computational testing of several putative structures, structure 3 was inferred for arsenicin C (C3H6As4OS) by comparing the experimental and density functional theory (DFT)-calculated 1H and 13C NMR spectra. Finally, the absolute configurations of 2 and 3 were determined with a combined use of experimental and time-dependent (TD)-DFT calculated electronic circular dichroism (ECD) spectra and observed specific rotations. These findings pose great challenges for the investigation of the biosynthesis of these metabolites and the cycle of arsenic in Nature. Arsenicins B and C showed strong antimicrobial activities, especially against S. aureus, which is comparable to the reference compound gentamycin.

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Section: Introductionmentioning

confidence: 99%

New Sulfur-Containing Polyarsenicals from the New Caledonian Sponge Echinochalina bargibanti

et al. 2018

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“…Arsenical compounds are among the oldest therapeutic agents used for the treatment of a variety of human diseases [ 5 , 6 ]. Although known for its toxicity and carcinogenicity, arsenic is present in the chemical structure of known drugs.…”

Section: Introductionmentioning

confidence: 99%

Expanding the Chemical Space of Arsenicin A-C Related Polyarsenicals and Evaluation of Some Analogs as Inhibitors of Glioblastoma Stem Cell Growth

et al. 2023

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The marine polyarsenical metabolite arsenicin A is the landmark of a series of natural and synthetic molecules characterized by an adamantane-like tetraarsenic cage. Arsenicin A and related polyarsenicals have been evaluated for their antitumor effects in vitro and have been proven more potent than the FDA-approved arsenic trioxide. In this context, we have expanded the chemical space of polyarsenicals related to arsenicin A by synthesizing dialkyl and dimethyl thio-analogs, the latter characterized with the support of simulated NMR spectra. In addition, the new natural arsenicin D, the scarcity of which in the Echinochalina bargibanti extract had previously limited its full structural characterization, has been identified by synthesis. The dialkyl analogs, which present the adamantane-like arsenicin A cage substituted with either two methyl, ethyl, or propyl chains, were efficiently and selectively produced and evaluated for their activity on glioblastoma stem cells (GSCs), a promising therapeutic target in glioblastoma treatment. These compounds inhibited the growth of nine GSC lines more potently than arsenic trioxide, with GI50 values in the submicromolar range, both under normoxic and hypoxic conditions, and presented high selectivity toward non-tumor cell lines. The diethyl and dipropyl analogs, which present favorable physical-chemical and ADME parameters, had the most promising results.

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