Stepharm LLC

Opelousas, LA, United States

Stepharm LLC

Opelousas, LA, United States

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Komati R.,University of New Orleans | Komati R.,Stepharm LLC | Jursic B.S.,University of New Orleans | Jursic B.S.,Stepharm LLC
Tetrahedron Letters | Year: 2014

A simple synthetic procedure for direct formamidation and amination of aryl halides mediated by copper(II) salts was developed in open air, without an external ligand in formamide with potassium carbonate as a base. This approach is particularly efficient when electron active aryl halides are used as substrates. In these cases almost quantitative formamidation was observed. © 2014 Elsevier Ltd. All rights reserved.


Hron R.,University of New Orleans | Hron R.,Stepharm LLC | Jursic B.S.,University of New Orleans | Jursic B.S.,Stepharm LLC
Tetrahedron Letters | Year: 2014

A simple synthetic procedure for the conversion of amines and hydrazines into substituted semicarbazides was developed. The initial condensation between the desired amine and phenyl chloroformate into phenyl carbamate is followed by the addition of hydrazine under basic conditions. The reaction is tolerable to a variety of functional groups, with mild conditions and high percent yields. © 2014 Elsevier Ltd. All rights reserved.


Backes G.L.,Louisiana State University Health Sciences Center | Jursic B.S.,University of New Orleans | Jursic B.S.,STEPHARM LLC. | Neumann D.M.,Louisiana State University Health Sciences Center
Bioorganic and Medicinal Chemistry | Year: 2015

Abstract Schiff base derivatives have recently been shown to possess antimicrobial activity, and these derivatives include a limited number of salicylaldehyde hydrazones. To further explore this structure-activity relationship between salicylaldehyde hydrazones and antifungal activity, we previously synthesized and analyzed a large series of salicylaldehyde and formylpyridinetrione hydrazones for their ability to inhibit fungal growth of both azole-susceptible and azole-resistant species of Candida. While many of these analogs showed excellent growth inhibition with low mammalian cell toxicity, their activity did not extend to azole-resistant species of Candida. To further dissect the structural features necessary to inhibit azole-resistant fungal species, we synthesized a new class of modified salicylaldehyde derivatives and subsequently identified a series of modified pyridine-based hydrazones that had potent fungicidal antifungal activity against multiple Candida spp. Here we would like to present our synthetic procedures as well as the results from fungal growth inhibition assays, mammalian cell toxicity assays, time-kill assays and synergy studies of these novel pyridine-based hydrazones on both azole-susceptible and azole-resistant fungal species. © 2015 Elsevier Ltd.


Neumann D.M.,Louisiana State University Health Sciences Center | Cammarata A.,Louisiana State University Health Sciences Center | Backes G.,Louisiana State University Health Sciences Center | Palmer G.E.,Immunology and Parasitology | And 2 more authors.
Bioorganic and Medicinal Chemistry | Year: 2014

Opportunistic fungal infections caused by the Candida spp. are the most common human fungal infections, often resulting in severe systemic infections - a significant cause of morbidity and mortality in at-risk populations. Azole antifungals remain the mainstay of antifungal treatment for candidiasis, however development of clinical resistance to azoles by Candida spp. limits the drugs' efficacy and highlights the need for discovery of novel therapeutics. Recently, it has been reported that simple hydrazone derivatives have the capability to potentiate antifungal activities in vitro. Similarly, pyrimidinetrione analogs have long been explored by medicinal chemists as potential therapeutics, with more recent focus being on the potential for pyrimidinetrione antimicrobial activity. In this work, we present the synthesis of a class of novel hydrazone-pyrimidinetrione analogs using novel synthetic procedures. In addition, structure-activity relationship studies focusing on fungal growth inhibition were also performed against two clinically significant fungal pathogens. A number of derivatives, including phenylhydrazones of 5-acylpyrimidinetrione exhibited potent growth inhibition at or below 10 μM with minimal mammalian cell toxicity. In addition, in vitro studies aimed at defining the mechanism of action of the most active analogs provide preliminary evidence that these compound decrease energy production and fungal cell respiration, making this class of analogs promising novel therapies, as they target pathways not targeted by currently available antifungals. © 2013 Elsevier Ltd. All rights reserved.


Backes G.L.,Louisiana State University Health Sciences Center | Neumann D.M.,Louisiana State University Health Sciences Center | Jursic B.S.,University of New Orleans | Jursic B.S.,STEPHARM LLC.
Bioorganic and Medicinal Chemistry | Year: 2014

Efficient synthetic procedures for the preparation of acid hydrazines and hydrazides were developed by converting the corresponding carboxylic acid into the methyl ester catalyzed by Amberlyst-15, followed by a reaction with hydrazine monohydrate. Sulfohydrazides were prepared from the corresponding sulfonyl chlorides and hydrazine monohydrate. Both of these group of compounds were condensed with substituted salicylaldehydes using gradient concentration methods that generated a large library of hydrazone, hydrazide and sulfohydrazide analogs. Antifungal activity of the prepared analogs showed that salicylaldehyde hydrazones and hydrazides are potent inhibitors of fungal growth with little to no mammalian cell toxicity, making these analogs promising new targets for future therapeutic development. © 2014 Elsevier Ltd. All rights reserved.

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