scholarly journals Inhibitory Effects of Sulfonamide Derivatives on the β-Carbonic Anhydrase (MpaCA) from Malassezia pachydermatis, a Commensal, Pathogenic Fungus Present in Domestic Animals

2021 ◽  
Vol 22 (22) ◽  
pp. 12601
Author(s):  
Viviana De Luca ◽  
Andrea Angeli ◽  
Valeria Mazzone ◽  
Claudia Adelfio ◽  
Fabrizio Carta ◽  
...  
Keyword(s):  
Pathogenic Fungus ◽  
Seborrheic Dermatitis ◽  
Co2 Concentration ◽  
Carbonic Anhydrases ◽  
Medical Sciences ◽  
Inhibitory Effects ◽  
Malassezia Pachydermatis ◽  
Sensing Systems ◽  
Promising Target ◽  
Reversible Hydration

Fungi are exposed to various environmental variables during their life cycle, including changes in CO2 concentration. CO2 has the potential to act as an activator of several cell signaling pathways. In fungi, the sensing of CO2 triggers cell differentiation and the biosynthesis of proteins involved in the metabolism and pathogenicity of these microorganisms. The molecular machineries involved in CO2 sensing constitute a promising target for the development of antifungals. Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial enzymes in the CO2 sensing systems of fungi, because they catalyze the reversible hydration of CO2 to proton and HCO3-. Bicarbonate in turn boots a cascade of reactions triggering fungal pathogenicity and metabolism. Accordingly, CAs affect microorganism proliferation and may represent a potential therapeutic target against fungal infection. Here, the inhibition of the unique β-CA (MpaCA) encoded in the genome of Malassezia pachydermatis, a fungus with substantial relevance in veterinary and medical sciences, was investigated using a series of conventional CA inhibitors (CAIs), namely aromatic and heterocyclic sulfonamides. This study aimed to describe novel candidates that can kill this harmful fungus by inhibiting their CA, and thus lead to effective anti-dandruff and anti-seborrheic dermatitis agents. In this context, current antifungal compounds, such as the azoles and their derivatives, have been demonstrated to induce the selection of resistant fungal strains and lose therapeutic efficacy, which might be restored by the concomitant use of alternative compounds, such as the fungal CA inhibitors.

scholarly journals Anion Inhibition Profile of the β-Carbonic Anhydrase from the Opportunist Pathogenic Fungus Malassezia Restricta Involved in Dandruff and Seborrheic Dermatitis

Metabolites ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 147 ◽  
Author(s):  
Prete ◽  
Angeli ◽  
Ghobril ◽  
Hitce ◽  
Clavaud ◽  
...  
Keyword(s):  
Pathogenic Fungus ◽  
Seborrheic Dermatitis ◽  
Selective Inhibition ◽  
Carbonic Anhydrases ◽  
Arsenic Acid ◽  
Architectural Features ◽  
Malassezia Globosa ◽  
Catalytic Mechanisms ◽  
Complexing Anions ◽  
Malassezia Restricta

Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes, which catalyze the crucial physiological CO2 hydration/dehydration reaction (CO2 + H2O ⇌ HCO3− + H+) balancing the equilibrium between CO2, H2CO3, HCO3− and CO32−. It has been demonstrated that their selective inhibition alters the equilibrium of the metabolites above affecting the biosynthesis and energy metabolism of the organism. In this context, our interest has been focalized on the fungus Malassezia restricta, which may trigger dandruff and seborrheic dermatitis altering the complex bacterial and fungal equilibrium of the human scalp. We investigated a rather large number of inorganic metal-complexing anions (a well-known class of CA inhibitors) for their interaction with the β-CA (MreCA) encoded by the M. restricta genome. The results were compared with those obtained for the two human ?-CA isoforms (hCAI and hCAII) and the β-CA from Malassezia globosa. The most effective MreCA inhibitors were diethyldithiocarbamate, sulfamide, phenyl arsenic acid, stannate, tellurate, tetraborate, selenocyanate, trithiocarbonate, and bicarbonate. The different KI values obtained for the four proteins investigated might be attributed to the architectural features of their catalytic site. The anion inhibition profile is essential for better understanding the inhibition/catalytic mechanisms of these enzymes and for designing novel types of inhibitors, which may have clinical applications for the management of dandruff and seborrheic dermatitis.

scholarly journals Effect of Sulfonamides and Their Structurally Related Derivatives on the Activity of ι-Carbonic Anhydrase from Burkholderia territorii

2021 ◽  
Vol 22 (2) ◽  
pp. 571
Author(s):  
Viviana De Luca ◽  
Andrea Petreni ◽  
Alessio Nocentini ◽  
Andrea Scaloni ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Selective Inhibition ◽  
Extensive Study ◽  
Protein Isoforms ◽  
Carbonic Anhydrases ◽  
Physiological Processes ◽  
Microbial Survival ◽  
Reversible Hydration

Carbonic anhydrases (CAs) are essential metalloenzymes in nature, catalyzing the carbon dioxide reversible hydration into bicarbonate and proton. In humans, breathing and many other critical physiological processes depend on this enzymatic activity. The CA superfamily function and inhibition in pathogenic bacteria has recently been the object of significant advances, being demonstrated to affect microbial survival/virulence. Targeting bacterial CAs may thus be a valid alternative to expand the pharmacological arsenal against the emergence of widespread antibiotic resistance. Here, we report an extensive study on the inhibition profile of the recently discovered ι-CA class present in some bacteria, including Burkholderia territorii, namely BteCAι, using substituted benzene-sulfonamides and clinically licensed sulfonamide-, sulfamate- and sulfamide-type drugs. The BteCAι inhibition profile showed: (i) several benzene-sulfonamides with an inhibition constant lower than 100 nM; (ii) a different behavior with respect to other α, β and γ-CAs; (iii) clinically used drugs having a micromolar affinity. This prototype study contributes to the initial recognition of compounds which efficiently and selectively inhibit a bacterial member of the ι-CA class, for which such a selective inhibition with respect to other protein isoforms present in the host is highly desired and may contribute to the development of novel antimicrobials.

scholarly journals Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

2021 ◽  
Vol 22 (11) ◽  
pp. 5482
Author(s):  
Zuo-Peng Zhang ◽  
Ye Zhong ◽  
Zhen-Bin Han ◽  
Lin Zhou ◽  
Hua-Sheng Su ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Human Cancer ◽  
Carbonic Anhydrases ◽  
Inhibitory Effects ◽  
Docking Analysis ◽  
Human Cancer Cell Lines ◽  
Hypoxic Conditions ◽  
Ca Ix ◽  
Topological Polar Surface Area ◽  
Ht 29

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.

scholarly journals Fungi of the genus Malassezia as opportunists of humans and animals

2018 ◽  
Vol 72 ◽  
pp. 359-375 ◽  
Author(s):  
Urszula Czyżewska ◽  
Magdalena Siemieniuk ◽  
Marek Bartoszewicz ◽  
Adam Tylicki
Keyword(s):  
Extracellular Enzymes ◽  
Cell Structure ◽  
Seborrheic Dermatitis ◽  
Epidemiological Data ◽  
Protein Profiling ◽  
Specific Cell ◽  
Malassezia Pachydermatis ◽  
Malassezia Folliculitis ◽  
Malassezia Spp

Yeasts from the genus Malassezia are common commensals and pathogens found in humans and animals, and are responsible for tinea cases. Due to their specific cell structure, they may be resistant to environmental stresses and difficult to eliminate by the host’s immune system. In spite of several virulence factors, the pathogenicity of Malassezia spp. and their interactions with hosts still arouse great interest. Genomes of particular isolates, representing the majority of species from the Malassezia genus, have been sequenced in recent years. Moreover, reconstruction of the phylogeny, by the usage of ITS and IGS sequences, has been attempted as well. Biochemical analyzes led to a better understanding of those fungi’s ecology and virulence. Lipid and protein profiling, the assessment of phospholipases and extracellular enzymes activities, brought new insight into the genesis and courses of diverse illnesses, including pityriasis versicolor, seborrheic dermatitis, atopic dermatitis, Malassezia folliculitis, psoriasis and systemic fungemia. Special attention should be paid to Malassezia pachydermatis, which is a potential model of zoophilic species with an increasing frequency of tinea cases caused in humans. Furthermore, in vitro experiments suggest its possible drug resistance. The members of Malassezia genus are a serious medical and therapeutic challenge. Because of difficulties in the assessment of their virulence, high genetic and biochemical diversity and, finally, complicated evolutionary traits, they require further research. Genomic and proteomic analyses, supported with biochemical profiling and epidemiological data, will contribute to a better understanding of the biology of the yeasts, especially the issue of opportunism among fungi.

scholarly journals Fusarisolins A–E, Polyketides from the Marine-Derived Fungus Fusarium solani H918

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 125 ◽  
Author(s):  
Siwen Niu ◽  
Xi-Xiang Tang ◽  
Zuowang Fan ◽  
Jin-Mei Xia ◽  
Chun-Lan Xie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Antifungal Activity ◽  
Fusarium Solani ◽  
Spectroscopic Data ◽  
Coenzyme A ◽  
Pathogenic Fungus ◽  
Chemical Conversion ◽  
Inhibitory Effects ◽  
Data Analyses ◽  
Naturally Occurring

Five new (fusarisolins A–E, 1 to 5) and three known (6 to 8) polyketides were isolated from the marine-derived fungus Fusarium solani H918, along with six known phenolics (9 to 14). Their structures were established by comprehensive spectroscopic data analyses, methoxyphenylacetic acid (MPA) method, chemical conversion, and by comparison with data reported in the literature. Compounds 1 and 2 are the first two naturally occurring 21 carbons polyketides featuring a rare β- and γ-lactone unit, respectively. All isolates (1 to 14) were evaluated for their inhibitory effects against tea pathogenic fungus Pestalotiopsis theae and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase gene expression. Compound 8 showed potent antifungal activity with an ED50 value of 55 μM, while 1, 8, 13, and 14 significantly inhibited HMG-CoA synthase gene expression.

scholarly journals Carbonic Anhydrases inhibitory effects of new benzenesulfonamides synthesized by using superacid chemistry

2011 ◽  
Vol 27 (6) ◽  
pp. 886-891 ◽  
Author(s):  
Fei Liu ◽  
Agnès Martin-Mingot ◽  
F. Lecornué ◽  
Marie-Paule Jouannetaud ◽  
Alfonso Maresca ◽  
...  
Keyword(s):  
Carbonic Anhydrases ◽  
Inhibitory Effects

scholarly journals Fluorescent Silica Nanoparticles with Multivalent Inhibitory Effects towards Carbonic Anhydrases

2015 ◽  
Vol 21 (29) ◽  
pp. 10249-10249 ◽  
Author(s):  
Nadia Touisni ◽  
Nasreddine Kanfar ◽  
Sébastien Ulrich ◽  
Pascal Dumy ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Carbonic Anhydrases ◽  
Inhibitory Effects ◽  
Fluorescent Silica Nanoparticles

scholarly journals Carbonic Anhydrase Inhibitors and Epilepsy: State of the Art and Future Perspectives

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6380
Author(s):  
Lidia Ciccone ◽  
Chiara Cerri ◽  
Susanna Nencetti ◽  
Elisabetta Orlandini
Keyword(s):  
Ionic Composition ◽  
Rapid Change ◽  
Carbonic Anhydrases ◽  
Brain Disorder ◽  
Ph Buffering ◽  
Treatment Of Epilepsy ◽  
Relevant Role ◽  
Spontaneous Recurrent Seizures ◽  
Reversible Hydration ◽  
Intracellular Potassium Concentration

Carbonic anhydrases (CAs) are a group of ubiquitously expressed metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3. Thus, they are involved in those physiological and pathological processes in which cellular pH buffering plays a relevant role. The inhibition of CAs has pharmacologic applications for several diseases. In addition to the well-known employment of CA inhibitors (CAIs) as diuretics and antiglaucoma drugs, it has recently been demonstrated that CAIs could be considered as valid therapeutic agents against obesity, cancer, kidney dysfunction, migraine, Alzheimer’s disease and epilepsy. Epilepsy is a chronic brain disorder that dramatically affects people of all ages. It is characterized by spontaneous recurrent seizures that are related to a rapid change in ionic composition, including an increase in intracellular potassium concentration and pH shifts. It has been reported that CAs II, VII and XIV are implicated in epilepsy. In this context, selective CAIs towards the mentioned isoforms (CAs II, VII and XIV) have been proposed and actually exploited as anticonvulsants agents in the treatment of epilepsy. Here, we describe the research achievements published on CAIs, focusing on those clinically used as anticonvulsants. In particular, we examine the new CAIs currently under development that might represent novel therapeutic options for the treatment of epilepsy.

scholarly journals An unprecedent prevalence of palmoplantar warts among nursing students

2020 ◽  
Vol 7 (1) ◽  
pp. 44
Author(s):  
M. Vijaya Bharathi ◽  
Neetha L. ◽  
S. Murugan ◽  
S. Rajagopal ◽  
J. Nivin Simon
Keyword(s):  
Nursing Students ◽  
Skin Diseases ◽  
Seborrheic Dermatitis ◽  
First Year ◽  
Medical Sciences ◽  
First Year Students ◽  
Common Skin ◽  
Skin Conditions ◽  
Nursing College ◽  
Hands And Feet

<p class="abstract"><strong>Background:</strong> Skin diseases are common contributors to disease morbidity worldwide, particularly among adolescents. Although skin diseases are rarely lethal, they can have a significant impact in terms of treatment cost, absence from school, and psychological distress. Verruca vulgaris (cutaneous warts) is a common skin problem in adolescents that commonly affects the hands and feet. The aim of the study was to determine the prevalence of warts among nursing students.</p><p class="abstract"><strong>Methods: </strong>Three hundred and twenty eight undergraduate degree students of nursing college were examined for skin conditions after an unprecedented sporadic visitors form the nursing college with palmo-plantar warts. The study was conducted at Sree Mookambika Institute of Medical Sciences, Kulasekharam, Kanyakumari district during the period of 20 March 2019 to 25 March 2019.</p><p class="abstract"><strong>Results: </strong>Among the 328 students, 102 students (31%) remained healthy dermatologically. Seborrheic dermatitis was found among 145 students (4.4%), pediculosis was found in 40 students (12%). 34 students were having palmoplantar warts (10.4%). Among these, nearly 30 were having palmar warts and only 4 were having plantar and palmar warts. 83 first year students were not having any warts in their hands or foot, whereas 11 among 2nd year, 16 among 3rd year students and 7 among 4th year students were having viral warts. Prevalence was more among 2nd and 3rd year students.</p><p class="abstract"><strong>Conclusions: </strong>Screening of hostel students should also include for the presence of viral skin disease like herpes simplex, Herpes zoster and HPV infections and they should be treated then and there to break the chain of transmission.</p>

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