Florida International University

Barry P Rosen

Masafumi Yoshinaga

Stanislaw F Wnuk

Md Abu Hasan Howlader

Sk Md Sazzad Hossain Suzol

Jun Li

Venkadesh Sarkarai Nadar

Guodong Niu

Kunie Yoshinaga-Sakurai

Certain embodiments of the invention pertain to a method of treating an infection in a subject caused by an infectious agent other than, the method comprising administering to the subject arsinothricin or a salt thereof. The infectious agent other thancan be a bacterium, protozoan, helminth, archaebacterium, or a fungus. In preferred embodiments, the infectious agent is, or. The invention also pertains to a method of treating an infection in a subject caused by an infectious agent, comprising administering to the subject arsinothricin or a salt thereof in combination with an inhibitor of phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase. In certain such embodiments, the infectious agent expresses phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase. Further embodiments provide compositions comprising arsinothricin or a salt thereof and an inhibitor of phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase.

Arsinothricin and methods of treating infections using arsinothricin

The subject invention provides organoarsenicals or salts thereof, compositions comprising an organoarsenical or a salt thereof, and methods of using the organoarsenicals or salts thereof, or compositions for inhibiting glutaminase and for treating cancers. Specifically, the subject invention provides methods of inhibiting glutaminase (e.g., KGA) catalytic activity in a cell, methods of treating cancer or a tumor via, for example, the inhibition of glutaminase activity, and methods of disrupting and/or inhibiting growth and proliferation of cancerous or tumorous cells.

Treatment of cancer using organoarsenicals

The subject invention provides arsinothricin (AST) or salts thereof, and compositions comprising AST or a salt thereof for use as multi-stage antimalarials. The subject invention also provides methods for treating, inhibiting and/or preventing malaria infection and transmission by using AST or salts thereof, or compositions comprising AST or a salt thereof. Advantageously, AST or a salt thereof inhibits glutamine synthetase (GS) of malaria pathogens without exhibiting cytotoxicity to human host.

Arsinothricin as a multi-stage antimalarial

The subject invention provides methods for the chemical synthesis of racemic arsinothricin (D,L-AST), the novel organoarsenical antibiotic. One is by condensation of the 2-chloroethyl(methyl)arsinic acid with acetamidomalonate, and the second involves reduction of the N-acetyl-protected derivative of hydroxyarsinothricin (AST-OH) and subsequent methylation of the resulting sodium salt of trivalent arsenic intermediate with methyl iodide. The enzyme AST N-acetyltransferase (ArsN1) was utilized to purify L-AST from racemic AST. This expedient chemical synthesis of AST provides a source of this novel antibiotic for future drug development.

Chemical synthesis of the organoarsenical antibiotic arsinothricin

The subject invention provides methods for the chemical synthesis of racemic arsinothricin (D,L-AST), the novel organoarsenical antibiotic. One is by condensation of the 2-chloroethyl(methyl)arsinic acid with acetamidomalonate, and the second involves reduction of the N-acetyl-protected derivative of hydroxyarsinothricin (AST-OH) and subsequent methylation of the resulting sodium salt of trivalent arsenic intermediate with methyl iodide. The enzyme AST N-acetyltransferase (ArsNl) was utilized to purify L-AST from racemic AST. This expedient chemical synthesis of AST provides a source of this novel antibiotic for future drug development.

The subject invention provides methods and procedures for synthesis and/or semi-synthesis of the novel antibiotic arsinothricin (AST) and derivatives. Arsinothricin (AST), a new broad-spectrum organoarsenical antibiotic, is a non-proteinogenic analog of glutamate that effectively inhibits glutamine synthetase. The subject invention provides chemical synthesis of an intermediate in the pathway of AST synthesis, hydroxyarsinothricin (AST-OH), which can be converted to AST by enzymatic methylation catalyzed by the ArsM As(III) S-adenosylmethionine methyltransferase. The methods provide a source of the novel antibiotic that will be required for future clinical trials. The subject invention also provides AST derivatives as a new class of antibiotics.

Synthesis of the organoarsenical antibiotic arsinothricin and derivatives thereof

Disclosed are methods of detecting organic arsenicals using genetically modified cells containing an arsR gene that encodes an AfArsR (As(III)-responsive repressor) protein and an arsenical resistance operon operably linked to a green fluorescent protein gene. The cell can produce a green fluorescent protein and fluoresce in the presence of trivalent organic arsenic. Trivalent organic arsenics can be one or more of phenylarsenite, travlent roaxarsone, and methylarsenite.

AfArsR gene and prokaryotic host cell

Disclosed are methods of detecting organic arsenicals using genetically modified cells.

Growing community of inventors

Boynton Beach, FL, United States of America

Barry P Rosen