University of Notre Dame Du Lac

Azevan Pharmaceuticals, Inc.

Klinikum Der Universitat Munchen

Hsiri Therapeutics, Inc.

Leibniz-institut Für Naturstoff-forschung Und Infektionsbiologie E.v. -hans-knöll-institut- (hki)

Moraski, Garrett

Miller, Marvin J.

Marvin J Miller

Garrett C Moraski

Gary A Koppel

George E Davis

Patricia Miller

Manuka Ghosh

Lowell D Markley

Ned D Heindel

Robert F Bruns, Jr

Cheng Ji

Ute Möllmann

Serena Carosso

Rohit Tiwari

Jonathan Stefely

Christophe D G Guillon

Chi-nung W Hsiao

Rui Liu

Matthew A Williams

Min Teng

Robert F Bruns

Jingdan Hu

Paul W Bohn

Florian Kloss

Yun-Ming Lin

Axel Brakhage

Patricia A Miller

Viktor Krchnak

Julia Dreisbach

Jiayun Hu

Kamil Philip Wojtas

Garret C Moraski

Sebastian Schieferdecker

Yanping Xu

Catherine M Gasparski

Julia M Dolence

Christophe D Guillon

Shifang Lu

Described is a biosensor for detection of analytes and methods of using the same for detecting bacterial infection in a subject. The biosensor comprises an array of gold nanoparticles, biotinylated polyethylene glycol thiol, polyethylene glycol thiol, at least one neutravidin molecule, and at least one affinity reagent immobilized on a surface of the at least one neutravidin molecule. The affinity reagent may be an aptamer or a siderophore. The biosensors demonstrate extraordinary selectively and sensitivity for rapid detection of whole-cell bacteria.

Biosensor and method for detection of analytes

Described herein are compounds and compositions, and methods of making and their use as effective agents against mycobacterial infections.

Benzyl amine-containing heterocyclic compounds and compositions useful against mycobacterial infection

Substituted nitrobenzothiazinones (BTZs) are potent antituberculosis prodrugs that are reductively activated to produce nitroso moieties that form covalent adducts with a cysteine residue of decaprenylphosphoryl-&#x3b2;-D-ribose-2'-oxi-dase (DprE1) of(Mtb). The resulting cell wall synthesis inhibition is lethal to Mtb, leading to consideration of development of BTZs for clinical use. The hydride-induced reduction of the nitroaromatic proceeds by reversible formation of the corresponding Meisenheimer complex. Herein we demonstrate that chemical reduction of BTZ043 with NaBD4 followed by reoxidation incorporates deuterium into the core nitro aromatic warhead. Subsequent reduction of the deuterated species is not affected, but, as expected, reoxidation is slowed by the deuterium isotope effect, thus prolonging the lifetime of the active nitroso oxidation state.

Deuterated antimicrobial compounds

Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic &#x3b2;-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N-hydroxy-2-azetidinones allowed incorporation of functionalized &#x3b1;-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure-activity-relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains ofwhich have been listed by the WHO as being of critical concern worldwide.

Antibacterial monobactams

The present invention relates to the general field of treatment of infectious diseases of mammals (humans and animals) caused by bacteria, in particular to the treatment of diseases like tuberculosis (TB), Buruli ulcer and leprosy caused by mycobacteria. The invention aims at the generation of a new series of benzothiazinone compounds having the potential to overcome the above mentioned problems. In a preferred embodiment the invention is concerned with compounds of the general formula (I) whereinRrepresents NO,Rrepresents CF,at least one of the substituents Rand Ris OH, SR, NHR, CN, N, a saturated or unsaturated, optionally halogenated, linear or branched aliphatic radical having 1-4 carbon atoms, linear or branched C-Calkoxy, C-Cacyl, and the other of Rand Rmay in addition be hydrogen,Rrepresents a 2-methyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl or a 4-(cyclo-hexylmethyl)piperazin-1-yl group andRand Rindependently of each other are hydrogen or a C-Calkyl group and/or a pharmaceutically acceptable salt thereof.

Antimicrobial compounds, their use for the treatment of mammalian infections and a new metabolic mechanism

A compound, comprising: an Fe(III)-binding and/or Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; and daptomycin covalently bound to the linker, or, if no linker is present, then to the siderophore; or pharmaceutically acceptable salt or solvate thereof.

Antibacterial sideromycins

A compound is provided, comprising: an Fe(III)-binding or an Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; a drug; and an Fe(III) to Fe(II) reduction triggered linker bound to the drug and the linker or, if no linker is present, then bound to the drug and the siderophore. Compositions and methods including the compound are also provided.

Reduction-triggered antibacterial sideromycins

Embodiments relate to the field of chemistry and biochemistry, and, more specifically, to imidazopyridine compounds, synthesis thereof, and methods of using same. Disclosed herein are various imidazo[1,2-a]pyhdine compounds and methods of using the novel compounds to treat or prevent tuberculosis in a subject or to inhibit fungal growth on plant species. Other embodiments include methods of synthesizing imidazo[1,2-a]pyridine compounds, such as the disclosed imidazo[1,2-a]pyridine compounds.

Imidazo [1,2-a]pyridine compounds, synthesis thereof, and methods of using same

The invention provides monobactams that can be used as antibacterial agents or intermediates for the preparation of other useful compounds such as antibacterial agents.

Peripherally substituted monocyclic beta-lactams

A compound, having the following formula: 

1,3-benzothiazinone, sulfoxide, and sulfone compounds with electrophilic substituent

Embodiments herein provide compounds and methods of making and using such compounds for prevention and treatment of multidrug resistant bacteria. In particular, embodiments are directed to anti-bacterial agents from benzo[d]heterocyclic scaffolds for prevention and treatment of multidrug resistant bacteria.

Benzoheterocyclic anti-bacterial agents

The invention provides a series of 5,5-heteroaromatic compounds, syntheses thereof, compositions thereof, and methods of using such compounds and compositions. Various embodiments provide methods of killing and/or inhibiting the growth ofand/or, and methods of treating, preventing, and/or amelioratingand/orinfections in a subject. In various embodiments, the 5,5-heteroaromatic compound is N-(4-(4-chlorophenoxy)benzyl)-2,6-dimethylimidazo[2,1-b]thiazole-5-carboxamide.

5,5-heteroaromatic anti-infective compounds

0-lactamyl alkanoic acids are described. Methods for treating various premenstrual disorders using or more &#x3b2;-lactamyl alkanoic acids are also described.

Beta-lactamylalkanoic acids for treating premenstrual disorders

Growing community of inventors

South Bend, IN, United States of America

Marvin J Miller