Arsenic in medicine: past, present and future

Paul, Ngozi P; Galván, Adriana E; Yoshinaga-Sakurai, Kunie; Rosen, Barry P.; Yoshinaga, Masafumi

doi:10.1007/s10534-022-00371-y

Cited by 57 publications

(53 citation statements)

References 161 publications

(227 reference statements)

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“…Discovery and development of new classes of antibiotics to prevent and reduce the emergence of antibiotic resistance are urgently needed. Arsenic is a double-edged sword: at high concentrations, it is a toxin and poison, while at lower concentrations, it has medicinal value . For example, inorganic arsenic trioxide (Trisenox) is a widely used chemotherapeutic drug used for the treatment of acute promyelocytic leukemia .…”

Section: Environmental Implicationsmentioning

confidence: 99%

“…Arsenic is a double-edged sword: at high concentrations, it is a toxin and poison, while at lower concentrations, it has medicinal value. 37 For example, inorganic arsenic trioxide (Trisenox) is a widely used chemotherapeutic drug used for the treatment of acute promyelocytic leukemia. 38 Aromatic arsenicals such as melarsoprol and roxarsone are antiprotozonan agents used for the treatment of trypanosomal diseases or prevention of coccidiosis in animal husbandry.…”

Section: ■ Environmental Implicationsmentioning

confidence: 99%

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Selective Methylation by an ArsM S-Adenosylmethionine Methyltransferase from Burkholderia gladioli GSRB05 Enhances Antibiotic Production

Chen

Galván

Viswanathan

et al. 2022

Environ. Sci. Technol.

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Arsenic methylation contributes to the formation and diversity of environmental organoarsenicals, an important process in the arsenic biogeochemical cycle. The arsM gene encoding an arsenite (As(III)) S-adenosylmethionine (SAM) methyltransferase is widely distributed in members of every kingdom. A number of ArsM enzymes have been shown to have different patterns of methylation. When incubated with inorganic As(III), Burkholderia gladioli GSRB05 has been shown to synthesize the organoarsenical antibiotic arsinothricin (AST) but does not produce either methylarsenate (MAs(V)) or dimethylarsenate (DMAs(V)). Here, we show that cells of B. gladioli GSRB05 synthesize DMAs(V) when cultured with either MAs(III) or MAs(V). Heterologous expression of the BgarsM gene in Escherichia coli conferred resistance to MAs(III) but not As(III). The cells methylate MAs(III) and the AST precursor, reduced trivalent hydroxyarsinothricin (R-AST-OH) but do not methylate inorganic As(III). Similar results were obtained with purified BgArsM. Compared with ArsM orthologs, BgArsM has an additional 37 amino acid residues in a linker region between domains. Deletion of the additional 37 residues restored As(III) methylation activity. Cells of E. coli co-expressing the BgarsL gene encoding the noncanonical radical SAM enzyme that catalyzes the synthesis of R-AST-OH together with the BgarsM gene produce much more of the antibiotic AST compared with E. coli cells co-expressing BgarsL together with the CrarsM gene from Chlamydomonas reinhardtii, which lacks the sequence for additional 37 residues. We propose that the presence of the insertion reduces the fitness of B. gladioli because it cannot detoxify inorganic arsenic but concomitantly confers an evolutionary advantage by increasing the ability to produce AST.

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Section: Environmental Implicationsmentioning

confidence: 99%

Section: ■ Environmental Implicationsmentioning

confidence: 99%

Selective Methylation by an ArsM S-Adenosylmethionine Methyltransferase from Burkholderia gladioli GSRB05 Enhances Antibiotic Production

Chen

Galván

Viswanathan

et al. 2022

Environ. Sci. Technol.

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“…Arsenic compounds have a long and complex relationship with human health, which has been recently reviewed [1,2]. Extensive toxicological and medicinal studies have been performed on compounds containing As(III) and As(V), including arsenic acid (H 3 AsO 4 ) and arsenous acid (H 3 AsO 3 ), their oxyanion conjugate bases, and their organic derivatives.…”

Section: Introductionmentioning

confidence: 99%

Realgar and arsenene nanomaterials as arsenic-based anticancer agents

Hollow

Johnstone²

2023

Current Opinion in Chemical Biology

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“…This compound is a heterocyclic arsenic-based small molecule (C 12 H 13 As 2 C l N 2 O 2 ) that was used to successfully treat syphilis and was marketed as Salvarsan (“lifesaving”) [ 1 ]. Despite the well-known toxicity of arsenic, this drug saved >560,000 lives within 50 years [ 2 ]. Bismuth, contrary to arsenic, is not toxic and is widely used as subsalicylate (C 7 H 5 BiO 4 ) in the well-known drug Pepto-Bismol [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Non-Antibiotic Antimony-Based Antimicrobials

et al. 2022

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A series of the eight novel organoantimony(V) cyanoximates of Sb(C6H5)4L composition was synthesized using the high-yield heterogeneous metathesis reaction between solid AgL (or TlL) and Sb(C6H5)4Br in CH3CN at room temperature. Cyanoximes L were specially selected from a large group of 48 known compounds of this subclass of oximes on the basis of their water solubility and history of prior biological activity. The synthesized compounds are well soluble in organic solvents and were studied using a variety of conventional spectroscopic and physical methods. The crystal structures of all reported organometallic compounds were determined and revealed the formation of the distorted trigonal bipyramidal environment of the Sb atom and monodentate axial binding of acido-ligands via the O atom of the oxime group. The compounds are thermally stable in the solid state and in solution molecular compounds. For the first time, this specially designed series of organoantimony(V) compounds is investigated as potential non-antibiotic antimicrobial agents against three bacterial and two fungal human pathogens known for their increasing antimicrobial resistance. Bacterial pathogens included Gram-negative Escherichia coli and Pseudomonas aeruginosa, and Gram-positive Staphylococcus aureus. Fungal pathogens included Cryptococcus neoformans and Candida albicans. The cyanoximates alone showed no antimicrobial impact, and the incorporation of the SbPh4 group enabled the antimicrobial effect. Overall, the new antimony compounds showed a strong potential as both broad- and narrow-spectrum antimicrobials against selected bacterial and fundal pathogens and provide insights for further synthetic modifications of the compounds to increase their activities.

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Arsenic in medicine: past, present and future

Cited by 57 publications

References 161 publications

Selective Methylation by an ArsM S-Adenosylmethionine Methyltransferase from Burkholderia gladioli GSRB05 Enhances Antibiotic Production

Selective Methylation by an ArsM S-Adenosylmethionine Methyltransferase from Burkholderia gladioli GSRB05 Enhances Antibiotic Production

Realgar and arsenene nanomaterials as arsenic-based anticancer agents

Non-Antibiotic Antimony-Based Antimicrobials

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