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Your search keyword '"Carter, David S."' showing total 4 results
Start Over Author "Carter, David S." Topic boron compounds
4 results on '"Carter, David S."'

1. Macrofilaricidal Benzimidazole-Benzoxaborole Hybrids as an Approach to the Treatment of River Blindness: Part 1. Amide Linked Analogs.

Author

Akama T, Freund YR, Berry PW, Carter DS, Easom EE, Jarnagin K, Lunde CS, Plattner JJ, Rock F, Stefanakis R, Fischer C, Bulman CA, Lim KC, Suzuki BM, Tricoche N, Mansour A, DiCosty U, McCall S, Carson B, McCall JW, McKerrow J, Hübner MP, Specht S, Hoerauf A, Lustigman S, Sakanari JA, and Jacobs RT

Subjects
Amides, Animals, Benzimidazoles pharmacokinetics, Boron Compounds pharmacokinetics, Female, Filaricides pharmacokinetics, Filaricides therapeutic use, Gerbillinae, Male, Onchocerca volvulus drug effects, Benzimidazoles therapeutic use, Boron Compounds therapeutic use, Brugia drug effects, Onchocerciasis drug therapy
Abstract

A series of benzimidazole-benzoxaborole hybrid molecules linked via an amide linker are described that exhibit good in vitro activity against Onchocerca volvulus , a filarial nematode responsible for the disease onchocerciasis, also known as river blindness. The lead identified in this series, 8a  (AN8799), was found to have acceptable pharmacokinetic properties to enable evaluation in animal models of human filariasis. Compound 8a was effective in killing Brugia malayi , B. pahangi , and Litomosoides sigmodontis worms present in Mongolian gerbils when dosed subcutaneously as a suspension at 100 mg/kg/day for 14 days but not when dosed orally at 100 mg/kg/day for 28 days. The measurement of plasma levels of 8a at the end of the dosing period and at the time of sacrifice revealed an interesting dependence of activity on the extended exposure for both 8a and the positive control, flubendazole.

Published
2020
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2. Macrofilaricidal Benzimidazole-Benzoxaborole Hybrids as an Approach to the Treatment of River Blindness: Part 2. Ketone Linked Analogs.

Author

Carter DS, Jacobs RT, Freund YR, Berry PW, Akama T, Easom EE, Lunde CS, Rock F, Stefanakis R, McKerrow J, Fischer C, Bulman CA, Lim KC, Suzuki BM, Tricoche N, Sakanari JA, Lustigman S, and Plattner JJ

Subjects
Administration, Oral, Animals, Benzimidazoles pharmacokinetics, Boron Compounds pharmacokinetics, Disease Models, Animal, Female, Filaricides pharmacokinetics, Filaricides therapeutic use, Gerbillinae, Male, Benzimidazoles therapeutic use, Boron Compounds therapeutic use, Ketones chemistry, Onchocerciasis, Ocular drug therapy
Abstract

The optimization of a series of benzimidazole-benzoxaborole hybrid molecules linked via a ketone that exhibit good activity against Onchocerca volvulus , a filarial nematode responsible for the disease onchocerciasis, also known as river blindness, is described. The lead identified in this series, 21 (AN15470), was found to have acceptable pharmacokinetic properties to enable an evaluation following oral dosing in an animal model of onchocerciasis. Compound 21 was effective in killing worms implanted in Mongolian gerbils when dosed orally as a suspension at 100 mg/kg/day for 14 days but not when dosed orally at 100 mg/kg/day for 7 days.

Published
2020
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3. Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model.

Author

Robertson GT, Ektnitphong VA, Scherman MS, McNeil MB, Dennison D, Korkegian A, Smith AJ, Halladay J, Carter DS, Xia Y, Zhou Y, Choi W, Berry PW, Mao W, Hernandez V, Alley MRK, Parish T, and Lenaerts AJ

Subjects
Animals, Bacterial Load drug effects, Disease Models, Animal, Drug Development, Female, Isoniazid pharmacology, Lung pathology, Mice, Mice, Inbred C3H, Microbial Sensitivity Tests, Tuberculosis, Pulmonary microbiology, Antitubercular Agents pharmacology, Aza Compounds pharmacology, Boron Compounds pharmacology, Hydrocarbons, Fluorinated pharmacology, Inhibins antagonists & inhibitors, Mycobacterium tuberculosis drug effects, Tuberculosis, Pulmonary drug therapy
Abstract

AN12855 is a direct, cofactor-independent inhibitor of InhA in Mycobacterium tuberculosis In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency than isoniazid. AN12855 drug levels were better retained in necrotic lesions and caseum where the majority of hard to treat, extracellular bacilli reside. Owing to these combined attributes, AN12855 represents a promising alternative to the frontline antituberculosis agent isoniazid., (Copyright © 2019 Robertson et al.)

Published
2019
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4. The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis.

Author

Korkegian A, O'Malley T, Xia Y, Zhou Y, Carter DS, Sunde B, Flint L, Thompson D, Ioerger TR, Sacchettini J, Alley MRK, and Parish T

Subjects
Bacterial Proteins antagonists & inhibitors, Bacterial Proteins genetics, Bacterial Proteins metabolism, Boron Compounds chemistry, Boron Compounds toxicity, Bridged Bicyclo Compounds, Heterocyclic chemistry, Bridged Bicyclo Compounds, Heterocyclic toxicity, Dose-Response Relationship, Drug, Drug Resistance, Bacterial, Humans, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis enzymology, Mycobacterium tuberculosis genetics, NADH Dehydrogenase antagonists & inhibitors, NADH Dehydrogenase genetics, NADH Dehydrogenase metabolism, THP-1 Cells, Boron Compounds pharmacology, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Mycobacterium tuberculosis drug effects
Abstract

We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC 90 ) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC 50  > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2018
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