Giuseppe Gumina’s research while affiliated with Presbyterian College and other places

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Publications (57)


Antimicrobial and nonantimicrobial sulfonamides in the United States [2].
Sulfonamide Allergies
  • Literature Review
  • Full-text available

September 2019

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2,330 Reads

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64 Citations

Pharmacy

Amber Giles

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Evan Lantz

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Giuseppe Gumina

As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic options for the empiric and definitive treatment of various infectious diseases. In the general population, approximately 3–8% of patients are reported to experience a sulfonamide allergy. Sulfonamide allergies can result in various physical manifestations; however, rash is reported as the most frequently observed. In patients with human immunodeficiency virus (HIV), dermatologic reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently compared to immunocompetent patients. This article describes the incidence, manifestations, and risk factors associated with sulfonamide allergies. The potential for cross-reactivity of allergies to sulfonamide antimicrobials with nonantimicrobial sulfonamide medications is also reviewed. Data suggest that substitutions at the N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiety. For patients with an indication for a sulfonamide antimicrobial with a listed allergy, it is important for healthcare practitioners to adequately assess the allergic reaction to determine appropriate management. Rechallenge and desensitization strategies may be appropriate for patients with delayed maculopapular eruptions, while alternative treatment options may be prudent for more severe reactions. Available data suggests a low risk of cross-allergenicity between sulfonamide antimicrobial and nonantimicrobial agents.

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Recent Advances in Drug Repurposing for Parkinson’s Disease

July 2018

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240 Reads

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11 Citations

Current Medicinal Chemistry

As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson's disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progress. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson's disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and time-efficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson's disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson's disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson's disease will be discussed.


Synthesis, Stereochemical Characterization, and Antimicrobial Evaluation of a Potentially Nonnephrotoxic 3′- C -acethydrazide Puromycin Analog

January 2017

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28 Reads

Nucleosides Nucleotides & Nucleic Acids

Josh Carter

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Blair A. Weaver

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Maria A. Chiacchio

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[...]

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Giuseppe Gumina

Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin's amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3′-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside. Evaluation of the title compound on Staphylococcus epidermidis and multi-drug resistance Staphylococcus aureus did not show significant antimicrobial activity up to a 400 μM concentration.


Effects of JWH015 in cytokine secretion in primary human keratinocytes and fibroblasts and its suitability for topical/transdermal delivery

January 2017

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3,400 Reads

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30 Citations

Molecular Pain

Background JWH015 is a cannabinoid (CB) receptor type 2 agonist that produces immunomodulatory effects. Since skin cells play a key role in inflammatory conditions and tissue repair, we investigated the ability of JWH015 to promote an anti-inflammatory and pro-wound healing phenotype in human primary skin cells. Methods Human primary keratinocytes and fibroblasts were stimulated with lipopolysaccharide. The mRNA expression of cannabinoid receptors was determined using RT-PCR. The effects of JWH015 (0.05, 0.1, 0.5, and 1 µM) in pro- and anti-inflammatory factors were tested in lipopolysaccharide-stimulated cells. A scratch assay, using a co-culture of keratinocytes and fibroblasts, was used to test the effects of JWH015 in wound healing. In addition, the topical and transdermal penetration of JWH015 was studied in Franz diffusion cells using porcine skin and LC-MS. Results The expression of CB1 and CB2 receptors (mRNA) and the production of pro- and anti-inflammatory factors enhanced in keratinocytes and fibroblasts following lipopolysaccharide stimulation. JWH015 reduced the concentration of major pro-inflammatory factors (IL-6 and MCP-1) and increased the concentration of a major anti-inflammatory factor (TGF-β) in lipopolysaccharide-stimulated cells. JWH015 induced a faster scratch gap closure. These JWH015’seffects were mainly modulated through both CB1 and CB2 receptors. Topically administered JWH015 was mostly retained in the skin and displayed a sustained and low level of transdermal permeation. Conclusions Our findings suggest that targeting keratinocytes and fibroblasts with cannabinoid drugs could represent a therapeutic strategy to resolve peripheral inflammation and promote tissue repair.


Recent Advances in the Rational Design and Optimization of Antibacterial Agents

September 2016

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883 Reads

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21 Citations

Medicinal Chemistry Communication

This review discusses next-generation antibacterial agents developed using rational, or targeted, drug design strategies. The focus of this review is on small-molecule compounds that have been designed to bypass developing bacterial resistance, improve the antibacterial spectrum of activity, and/or to optimize other properties, including physicochemical and pharmacokinetic properties. Agents are discussed that affect known antibacterial targets, such as the bacterial ribosome, nucleic acid binding proteins, and proteins involved in cell-wall biosynthesis; as well as some affecting novel bacterial targets which do not have currently marketed agents. The discussion of the agents focuses on the rational design strategies employed and the synthetic medicinal chemistry and structure-based design techniques utilized by the scientists involved in the discoveries, including such methods as ligand- and structure-based strategies, structure-activity relationship (SAR) expansion strategies, and novel synthetic organic chemistry methods. As such, the discussion is limited to small-molecule therapeutics that have confirmed macromolecular targets and encompasses only a fraction of all antibacterial agents recently approved or in late-stage clinical trials. The antibacterial agents selected have been recently approved for use on the U.S. or European markets or have shown promising results in phase 2 or phase 3 U.S. Clinical trials:


Synthetic studies toward 3’-C-puromycin analogs

April 2016

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13 Reads

Chemical Data Collections

We devised a synthetic scheme based on a Horner–Wadsworth–Emmons olefination followed by a stereoselective reduction in the attempt to synthesize a puromycin analog that cannot be metabolized to a known nephrotoxic 3’-aminonucleoside. This procedure allowed the synthesis of a fully protected nucleoside precursor of the target molecule. However, the last step proceeded with a surprising outcome, providing a dimethyl amide instead of the expected amino ketone derivative.



Synthetic strategy toward γ-KETO NITRILES and their Biocatalytic conversion to asymmetric γ-lactones

August 2013

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82 Reads

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8 Citations

Synthesis

Asymmetric gamma-hydroxy nitriles are valuable intermediates because hydrolysis of the nitriles can result in an intramolecular cyclization to chiral gamma-lactones, which have a variety of biological uses. Starting with an assortment of different aldehydes (alkyl and aryl) a 4-step synthesis of gamma-keto nitriles was developed. These pro-chiral substrates were then screened against a library of ketoreductases for their ability to stereoselectively reduce the carbonyl. Enzymes from the short chain dehydrogenase family showed activity and these enzymatic reactions were scaled up to produce a diverse set of chiral gamma-lactones.


Structure-activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae

November 2012

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471 Reads

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125 Citations

Dengue fever is a severe public health problem for several countries. In order to find effective larvicides to aid control programs, the structure-activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae were evaluated. Additionally, the composition and larvicidal activity of Syzygium aromaticum essential oil was assessed. Four compounds representing 99.05% of S. aromaticum essential oil have been identified. The essential oil was active against Ae. aegypti larvae (LC(50) = 62.3 and 77.0 ppm, field-collected and Rockefeller larvae respectively). The larvicidal activity of eugenol, the major compound of the essential oil, was further evaluated (LC(50) = 93.3 and 71.9 ppm, field-collected and Rockefeller larvae respectively). The larvicidal activity and structure-activity relationships of synthetic derivatives of eugenol were also assessed. The larvicidal activity of the derivatives varied between 62.3 and 1614.9 ppm. Oxidation of eugenol allylic bond to a primary alcohol and removal of the phenolic proton resulted in decreased potency. However, oxidation of the same double bond in 1-benzoate-2-methoxy-4-(2-propen-1-yl)-phenol resulted in increased potency. Structural characteristics were identified that may contribute to the understanding of the larvicidal activity of phenylpropanoids. The present approach may help future work in the search for larvicidal compounds. Copyright © 2012 Society of Chemical Industry.



Citations (36)


... In 2000, Balas and Boren estimated that it took approximately 15 years from the publication of landmark clinical trials to strongly affect clinical practice, and an average of 9.3 years to implement evidence from reviews, papers, and textbooks [20]. Accordingly, a plausible explanation of the lower avoidance rate among our younger respondents may be related to the fact that, although sulfonamide cross-reactivity retrospective landmark studies were reported within the last twenty years [15,16,18], several comprehensive review articles discussing the lack of evidence of cross-allergenicity between SA and NAS have been published within the past decade [12,13,21,22]. ...

Reference:

Prescribing carbonic anhydrase inhibitors to patients with “sulfa” antibiotics allergy: do we dare?
Sulfonamide Allergies

Pharmacy

... In 2016, 6.1 million people were afflicted with PD worldwide, and 211 296 deaths were recorded in that year due to this disease. By 2040, it is estimated that approximately 13 million individuals across the globe will be affected by this disease, which brings high social and economic costs to society [1,2]. For this reason, extensive research has been conducted to find novel medicinal therapies for this disease. ...

Recent Advances in Drug Repurposing for Parkinson’s Disease
  • Citing Article
  • July 2018

Current Medicinal Chemistry

... database; these studies have focused on new therapeutic protocols with existing drugs or the use of active substances with known antifibrotic and/or antiinflammatory effects, such as cannabinoids (CBs), for treatment of IPF (Heukels et al., 2019;Liu et al., 2022). CB1 (CB1R) (Gkoumassi et al., 2007;Servettaz et al., 2010;Karmaus et al., 2013;Liu et al., 2014a;Bronova et al., 2015;Staiano et al., 2016;Cinar et al., 2017;Muthumalage and Rahman, 2019;Mohammed et al., 2020;Zawatsky et al., 2020;Chen et al., 2022) and CB2 (CB2R) (Gkoumassi et al., 2007;Servettaz et al., 2010;Costola-de-Souza et al., 2013;Karmaus et al., 2013;Staiano et al., 2016;Bort et al., 2017;Liu and Shi, 2019;Muthumalage and Rahman, 2019;Liu et al., 2020;Parlar et al., 2021;Liu et al., 2022) receptor agonists exhibit inflammation-modulating (Gkoumassi et al., 2007;Costola-de-Souza et al., 2013;Karmaus et al., 2013;Liu et al., 2014b;Staiano et al., 2016;Bort et al., 2017;Cinar et al., 2017;Liu and Shi, 2019;Muthumalage and Rahman, 2019;Liu et al., 2020;Mohammed et al., 2020;Zawatsky et al., 2020;Parlar et al., 2021;Liu et al., 2022) and antifibrotic effects (Servettaz et al., 2010;Bronova et al., 2015;Liu and Shi, 2019;Chen et al., 2022) in lung tissue or bronchoalveolar lavage fluid (BALF) by focusing on inflammation markers, including transforming growth factor-β1 (TGF-β1), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and collagen type I (ColI) in human bronchial epithelial cells (Gkoumassi et al., 2007;Muthumalage and Rahman, 2019), human embryonic lung fibroblasts (Liu and Shi, 2019;Muthumalage and Rahman, 2019), and monocyte and lung resident macrophages (Staiano et al., 2016;Muthumalage and Rahman, 2019). In addition, human bronchial epithelial cells (Gkoumassi et al., 2007;Boyacioglu et al., 2021), lung macrophages (Staiano et al., 2016), and mice lung tissue (Tahamtan et al., 2018;Huang et al., 2020) express CB receptors (CBRs). ...

Effects of JWH015 in cytokine secretion in primary human keratinocytes and fibroblasts and its suitability for topical/transdermal delivery

Molecular Pain

... Quinolone derivatives are compounds used as a range of antibiotics [1,2]. Thus, a number of antibiotics have been developed based on them, such as levofloxacin [3,4], moxifloxacin [5], gemifloxacin [6,7], ciprofloxacin [8,9], and so on ( Figure 1). ...

Recent Advances in the Rational Design and Optimization of Antibacterial Agents

Medicinal Chemistry Communication

... This type of substitution gives the potential of endowing novel electrostatic interactions to the modified compound. Due to these properties, fluorine substitution has been observed to be effective at modulating the activity of many anti-HIV and -HBV nucleoside analogues (Herdewijn et al., 1987; Schinazi et al., 1992b; Lin et al., 1994; Lin et al., 1996; Chen et al., 1998; Chu et al., 1998; Dutschman et al., 1998; Lee et al., 1999; Shi et al., 1999; Lee et al., 2002). Modifications include substitution of the 2′-or 3′-position of the deoxyribose ring in order to either mimic the presence of a 3′-hydroxyl or to stabilize the nucleoside (Herdewijn et al., 1987; Lee et al., 1999; Lee et al., 2002). ...

Structure-activity relationships of D- and L-3 '-fluoro-2 ',3 '-unsaturated nucleosides as anti-HIV agents.
  • Citing Conference Paper
  • February 2003

Antiviral Research

... The first phosphorylation is typically mediated by viral kinases such as thymidine kinases (TK) of herpes viruses. For viruses such as HIV and hepatitis B virus that cannot produce virus-encoded TK, cellular kinases are required as the initial step to convert nucleoside analogs into monophosphorylated products [97]. The process mediated by viral kinases is considered more efficient than that of cellular kinases because virus-encoded TK has a higher affinity for their substrate. ...

Recent Advances in Antiviral Nucleosides
  • Citing Chapter
  • December 2003

... Some examples are known where the introduction of cyano group either on the base moiety or on the sugar ring has led to a significant change in biological activity [100]. A number of cyano ribofuranoses have displayed potent antiviral [101,102] and anticancer activities [103]. ...

Synthesis and anti-HIV Activity of L-β-3′-C-Cyano-2′,3′-unsaturated Nucleosides and L-3′-C-Cyano-3′-deoxyribonucleosides.
  • Citing Article
  • December 2003

ChemInform

... Conversely, it is widely recognized that Hdap holds significant pharmaceutical interest, as enzymatic oxidative deaminations transform it in guanine [17]. This characteristic presents opportunities for its use as a prodrug in important antiviral medications such as acyclovir, penciclovir, or entecavir. ...

Nucleoside and Nucleotide Prodrugs
  • Citing Article
  • July 2003

ChemInform

... The selective introduction of fluorine or fluorine-containing functional groups to small organic molecules has proven extremely useful in modifying the physicochemical and pharmacokinetic properties of small drug molecules [1][2][3]. In the field of nucleoside and nucleotide chemistry, fluorine substitutions to the 2 and 3 positions of the sugar moiety have been shown to dramatically affect both metabolic stability and biological activity [4][5][6]. This is not only due to the inherent strength of the C-F bond, which is highly resistant to metabolic cleavage but also to the polarizing effect of the fluoro group that influences the sugar pucker angle through the gauche effect [3,6]. ...

Synthesis and Potent Anti-HIV Activity of l -3‘-Fluoro-2‘,3‘Unsaturated Cytidine
  • Citing Article
  • December 2001

Organic Letters