New naphthoquinone thiazole hybrids as carbonic anhydrase and cholinesterase inhibitors: Synthesis, crystal structure, molecular docking, and acid dissociation constant

Efeoglu, Cagla; Selcuk, Ozge; Demir, Bunyamin; Sahin, Ertan; Sari, Hayati; Türkeş, Cüneyt; Demir, Yeliz; Nural, Yahya; Beydemir, Şükrü

doi:10.1016/j.molstruc.2023.137365

Cited by 8 publications

(4 citation statements)

References 82 publications

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“…[35] The residues of the active site that were ascertained using the SiteMap tool [36,37] were determined in the module for generating the receptor grid. [38,39] Before molecular docking, DOX and esculetin were also subjected to preparation to generate all possible 3D conformations and states under physiological pH conditions, [40] utilizing the LigPrep module. [41] The molecular docking process was carried out using the Glide XP method.…”

Section: Molecular Docking Studymentioning

confidence: 99%

Protective effects of esculetin against doxorubicin‐induced toxicity correlated with oxidative stress in rat liver: In vivo and in silico studies

Köroğlu,

Kizir,

Karaman

et al. 2024

J Biochem & Molecular Tox

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Doxorubicin (DOX) is widely used in cancer treatment but the dose‐related toxicity of DOX on organs including the liver limit its use. Therefore, there is great interest in combining DOX with natural compounds with antioxidant properties to reduce toxicity and increase drug efficacy. Esculetin is a natural coumarin derivative with biological properties encompassing anti‐inflammatory and antioxidant activities. In light of these properties, this study was meticulously crafted to investigate the potential of esculetin in preventing doxorubicin (DOX)‐induced hepatotoxicity in Sprague‐Dawley rats. The rats were divided into a total of six groups: control group, DOX group (administered DOX at a cumulative dose of 5 mg/kg intraperitoneally every other day for 2 weeks), E50 group (administered 50 mg/kg of esculetin intraperitoneally every day), E100 group (administered 100 mg/kg of esculetin intraperitoneally every day) and combined groups (DOX + E50 and DOX + E100) in which esculetin was administered together with DOX. The treatments, both with DOX alone and in combination with E50, manifested a reduction in catalase (CAT mRNA) levels in comparison to the control group. Notably, the enzymatic activities of superoxide dismutase (SOD), CAT, and glutathione peroxidase (GPx) witnessed significant decreases in the liver of rats treated with DOX. Moreover, DOX treatment induced a statistically significant elevation in malondialdehyde (MDA) levels, coupled with a concurrent decrease in glutathione (GSH) levels. Additionally, molecular docking studies were conducted. However, further studies are needed to confirm the hepatoprotective properties of esculetin and to precisely elucidate its mechanisms of action.

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Section: Molecular Docking Studymentioning

confidence: 99%

Protective effects of esculetin against doxorubicin‐induced toxicity correlated with oxidative stress in rat liver: In vivo and in silico studies

Köroğlu,

Kizir,

Karaman

et al. 2024

J Biochem & Molecular Tox

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“…XRD study showed that the compound ( 14a ) was crystalized in a triclinic crystal system adopting a P 1̄ space group and one unit cell consisting of two iminothiazoline molecules. 46…”

Section: Heterocyclization Reactionsmentioning

confidence: 99%

Exploring the latest trends in chemistry, structure, coordination, and diverse applications of 1-acyl-3-substituted thioureas: a comprehensive review

Ullah,

Saeed,

Azeem

et al. 2024

RSC Adv.

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“…These compounds used in research demonstrated significant inhibition of studied enzymes activities at low nanomolar concentrations. [16] In the study conducted by Korkmaz, compounds bearing the 2-aminothiazole structure were synthesized. The effects of the compounds on carbonic anhydrase I-II isoenzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were examined.…”

Section: Introductionmentioning

confidence: 99%

“…The cholinergic system is the main focus of current AD research, with emphasis on AChE inhibitors. [12] Excessive production of free radicals and reactive oxygen species (ROS) during metabolism can damage a variety of cellular macro-molecules, including proteins, membrane lipids, and nucleic acids, ultimately result in cell death. Antioxidants protect living organisms from the damaging effects of free radicals by reducing their production.…”

Section: Introductionmentioning

confidence: 99%

New Thiazole Derivatives: Carbonic Anhydrase I–II and Cholinesterase Inhibition Profiles, Molecular Docking Studies

Karakaya,

Ercetin,

Yıldırım

et al. 2024

ChemistrySelect

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Thiosemicarbazone derivative was obtained by the addition of thiosemicarbazide to 5‐nitro‐thiophene‐2‐carbaldehyde. The addition–cyclization of the 2‐bromoacetophenone derivative to thiosemicarbazone derivative gave the new thiazole derivatives (2 a‐k). Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), antioxidant, and human carbonic anhydrase (hCA) I and II isoform inhibitory activities of the thiazole derivatives 2 a‐k were investigated. The effects of thiazole derivatives on carbonic anhydrase I and II (hCA I–II) isoenzymes were examined in vitro using the esterase method. IC50 values for enzyme inhibition were found to be 2.661–22.712 μM for hCA I and 5.372–26.813 μM for hCA II. All derivatives reduced the activities of carbonic anhydrase I and II isoenzymes and were new potential inhibitor molecule candidates. These compounds were found to have minimal effects on AChE and BChE. The antioxidant properties of the target compounds were determined using DPPH and ferric ion‐chelating assays. In particular, compounds 2 k and 2 h had the highest antioxidant effect in the series with IC50 values of 30.11±0.008 μM and 30.21±0.006 μM, respectively. ADMET properties of the compounds found to be effective were evaluated and their interactions with the enzyme were determined by molecular docking.

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New naphthoquinone thiazole hybrids as carbonic anhydrase and cholinesterase inhibitors: Synthesis, crystal structure, molecular docking, and acid dissociation constant

Cited by 8 publications

References 82 publications

Protective effects of esculetin against doxorubicin‐induced toxicity correlated with oxidative stress in rat liver: In vivo and in silico studies

Protective effects of esculetin against doxorubicin‐induced toxicity correlated with oxidative stress in rat liver: In vivo and in silico studies

Exploring the latest trends in chemistry, structure, coordination, and diverse applications of 1-acyl-3-substituted thioureas: a comprehensive review

New Thiazole Derivatives: Carbonic Anhydrase I–II and Cholinesterase Inhibition Profiles, Molecular Docking Studies

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