Azole derivatives with naphthalene showing potent antifungal effects against planktonic and biofilm forms of Candida spp.: an in vitro and in silico study

Sarı, Suat; Koçak, Ebru; Kart, Didem; Özdemi̇r, Zeynep; Acar, Mustafa F; Sayoğlu, Burcu; Karakurt, Arzu; Dalkara, Sevim

doi:10.1007/s10123-020-00144-y

Cited by 9 publications

(7 citation statements)

References 40 publications

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“…Initially, 5 g was tested and not found significantly toxic to murine fibroblasts up to 100 μM for 24 h (Figure 2). Likewise, 5i and 5 k were previously found to show negligible toxicity (Sari et al, 2021) (see Supporting information for details).…”

Section: Resultsmentioning

confidence: 58%

Potential of nafimidone derivatives against co‐morbidities of epilepsy: In vitro, in vivo, and in silico investigations

Sarı

Barut

Marcinkowska

et al. 2021

Drug Development Research

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Nafimidone is known for its clinical antiepileptic effects and alcohol derivatives of nafimidone were reported be potent anticonvulsants. These compounds are structurally similar to miconazole, which is known to inhibit cholinesterases, protect neurons, and ameliorate cognitive decline. Herein, we aimed to reveal the potential of three nafimidone alcohol esters (5 g, 5i, and 5 k), which were previously reported for their anticonvulsant effects, against co‐morbidities of epilepsy such as inflammatory and neuropathic pain, cognitive and behavioral deficits, and neuron death, and understand their roles in related pathways such as γ‐butyric acid type A (GABAA) receptor and cholinesterases using in vitro, in vivo and in silico methods. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) test was used for cytotoxicity evaluation, hippocampal slice culture assay for neuroprotection, formalin test for acute and inflammatory pain, sciatic ligation for neuropathic pain, Morris water maze and open field locomotor tasks for cognitive and behavioral deficits, radioligand binding for GABAA receptor affinity, spectrophotometric methods for cholinesterase inhibition in vitro, and molecular docking in silico. The compounds were non‐toxic to fibroblast cells. 5 k was neuroprotective against kainic acid‐induced neuron death. 5i reduced pain response of mice in both the acute and the inflammatory phases. 5i improved survival upon status epilepticus. The compounds showed no affinity to GABAA receptor but inhibited acetylcholinesterase, 5 k also inhibited butyrylcholinesterase. The compounds were predicted to interact mainly with the peripheric anionic site of cholinesterase enzymes. The title compounds showed neuroprotective, analgesic, and cholinesterase inhibitory effects, thus they bear promise against certain co‐morbidities of epilepsy with neurological insults.

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Section: Resultsmentioning

confidence: 58%

Potential of nafimidone derivatives against co‐morbidities of epilepsy: In vitro, in vivo, and in silico investigations

Sarı

Barut

Marcinkowska

et al. 2021

Drug Development Research

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“…The active derivatives were mostly selective towards BChE over AChE, which could be seen as an important attribute to support the promise of azoles since BChE is believed to play a key role in regulating brain acetylcholine levels in the late stage of AD and BChE inhibition does not cause the gastrointestinal side effects associated with AChE inhibition [16] . On the other hand, it was interesting to see that the active derivatives were previously reported to show highly potent antifungal effects against pathogenic Candida species [9] …”

Section: Resultsmentioning

confidence: 80%

“…[16] On the other hand, it was interesting to see that the active derivatives were previously reported to show highly potent antifungal effects against pathogenic Candida species. [9] The Active Derivatives are Competitive Cholinesterase Inhibitors 19 and 20 were selected for enzyme kinetic studies with AChE, along with 7, 11, 12, and 16 with BChE, due to their low IC 50 values. Kinetic studies yielded low K i values for these derivatives as well (Table 2 and Figure 2), indicating strong engagement with the enzyme.…”

Section: The Imidazole Derivatives Proved Potent and Selective Bche I...mentioning

confidence: 99%

“…In one of these studies, the analogs possessed 2‐naphthyl as aryl group and proved neuroprotective in addition to their anticholinesterase benefits ( Figure 1). [8] In the current study, we present anticholinesterase evaluation of an azole library comprising oxime ether analogs of miconazole, which were previously designed as antifungal agents [9–13] . The library compounds possess 2‐naphthyl as the aryl group; imidazole, pyrazole, 1,2,4‐triazole, and 3,5‐dimethylpyrazole as the azole ring; and diverse aliphatic and aromatic substitutions including 2,4‐dichlorobenzyloxy as the tail group ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Antifungal Azole Derivatives Featuring Naphthalene Prove Potent and Competitive Cholinesterase Inhibitors with Potential CNS Penetration According to the in Vitro and in Silico Studies

Sarı

Akkaya

Zengin

et al. 2022

Chemistry & Biodiversity

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Cholinesterase inhibition is of great importance in the fight against neurodegenerative disorders such as Alzheimer's disease. Azole antifungals have come under the spotlight with recent discoveries that underline the efficacy and potential of miconazole and its derivatives against cholinesterase enzymes. In this study, we evaluated a library of azoles against acetylcholinesterase and butyrylcholinesterase using in vitro and in silico methods to identify potent inhibitors. Low micromolar IC50 values were obtained for imidazole derivatives, which were further tested and found potent competitive cholinesterase inhibitors via enzyme kinetics study. The active derivatives showed negligible toxicity in in vitro cytotoxicity tests. Molecular modeling studies predicted that these derivatives were druglike, could penetrate blood‐brain barrier, and tightly bind to cholinesterase active site making key interactions via the imidazole moiety at protonated state. Thus, current study identifies potent and competitive cholinesterase inhibitor azoles with minor toxicity and potential to pass into the central nervous system.

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“…In medicinal chemistry, naphthalene is a versatile unit that appears as a potential moiety in drug creation [46] because of the various biological actions induced by this scaffold. In this respect, antimicrobial, [47][48][49] anticancer, [50,51] antiviral, [52] anticonvulsant, [53] antitubercular, [54] and anti-inflammatory properties have been found for naphthalenebased compounds. [55] Furthermore, some naturally occurring compounds containing the naphthalene nucleus have demonstrated significant biological activity, including justicidin A (anticancer), [56] rifampicin (antitubercular), [57] patentiflorin A (anti-HIV), [58] and bis-ANS 82 (tubulin polymerization inhibitor).…”

Section: Introductionmentioning

confidence: 99%

Hantzsch‐Like Synthesis, DNA Photocleavage, DNA/BSA Binding, and Molecular Docking Studies of Bis(sulfanediyl)bis(tetrahydro‐5‐deazaflavin) Analogs Linked to Naphthalene Core

Ragheb

Abdelwahab

Darweesh

et al. 2022

Chemistry & Biodiversity

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The cyclocondensation reaction of aldehydes with dimedone and bis(6-aminopyrimidin-4-one) in acetic acid led to the formation of the corresponding bis (pyrimido[4,5-b]quinoline-4,6-diones) which are known as bis(sulfanediyl)bis(tetrahydro-5-deazaflavin) analogs in a single step. Also, bis(pyrimido[4,quinoline-4,6diones) which are linked to naphthyl core via phenoxymethyl linkage is prepared. The interactions of the synthesized compounds with DNA and bovine serum albumin (BSA) were studied. Gel electrophoresis assay was used to show the capability of the compounds to photocleave the supercoiled pBR322 plasmid DNA in UV-A (365 nm). Besides, the most photocleavable compound, bis(tetrahydropyrimido[4,5-b]quinoline-4,6-dione) linked to pyridin-3-yl at position-5 exhibits good binding affinities toward CT-DNA and BSA as supported by UV/VIS spectral studies. In addition to the experimental findings, a molecular docking simulation was performed to collect detailed binding data for this compound to both biomolecules.

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Azole derivatives with naphthalene showing potent antifungal effects against planktonic and biofilm forms of Candida spp.: an in vitro and in silico study

Cited by 9 publications

References 40 publications

Potential of nafimidone derivatives against co‐morbidities of epilepsy: In vitro, in vivo, and in silico investigations

Potential of nafimidone derivatives against co‐morbidities of epilepsy: In vitro, in vivo, and in silico investigations

Antifungal Azole Derivatives Featuring Naphthalene Prove Potent and Competitive Cholinesterase Inhibitors with Potential CNS Penetration According to the in Vitro and in Silico Studies

Hantzsch‐Like Synthesis, DNA Photocleavage, DNA/BSA Binding, and Molecular Docking Studies of Bis(sulfanediyl)bis(tetrahydro‐5‐deazaflavin) Analogs Linked to Naphthalene Core

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