A novel series of thiosemicarbazone hybrid scaffolds: Design, synthesis, DFT studies, metabolic enzyme inhibition properties, and molecular docking calculations

Yakan, Hasan; Muğlu, Halit; Türkeş, Cüneyt; Demir, Yeliz; Erdoğan, Musa; Çavuş, M. Serdar; Beydemır, Şükrü

doi:10.1016/j.molstruc.2023.135077

Cited by 23 publications

(25 citation statements)

References 118 publications

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“…In our other work, by combining different isocyanates with 4‐hydroxy‐3,5‐dimethoxy benzaldehyde, new thiosemicarbazones carrying the Schiff base ( 1 – 13 ) were produced. The compounds showed highly potent inhibition effect with K I values are in the range of 51.11–78.10 nM for AChE, 60.32–300.00 nM for h CA I, and 64.21–307.70 nM, for h CA II [32] . Hasmi et al [38] .…”

Section: Resultsmentioning

confidence: 93%

“…The most active N ‐(2‐chlorophenyl)‐2‐(4‐hydroxy‐3,5‐dimethoxybenzylidene)hydrazine‐1‐carbothioamide showed with K I values of 60.32±9.78 nM [31] . In our other work, thiosemicarbazones bearing the Schiff base showed highly potent inhibition effect with K I values are in the range of 51.11–78.10 nM for AChE, 60.32–300.00 nM for h CA I, and 64.21–307.70 nM, for h CA II (Scheme 1b) [32] . In another work, thiosemicarbazone derivatives based 3‐ethoxysalicylaldehyde assayed against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α‐glycosidase (Scheme 1c).…”

Section: Introductionmentioning

confidence: 73%

“…[31] In our other work, thiosemicarbazones bearing the Schiff base showed highly potent inhibition effect with K I values are in the range of 51.11-78.10 nM for AChE, 60.32-300.00 nM for hCA I, and 64.21-307.70 nM, for hCA II (Scheme 1b). [32] In another work, thiosemicarbazone derivatives based 3-ethoxysalicylaldehyde assayed against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase (Scheme 1c). The results existing they effectively inhibited AChE, with K I values in the range of 385.38 � 45.03 to 983.04 � 104.64 nM.…”

Section: Introductionmentioning

confidence: 99%

“…[30] There are many organic compounds in the literature have been tested in the effects of on the inhibition of CAs and AChE enzymes. [31][32][33][34][35] In our former work, thiosemicarbazone derivatives exhibited highly potent inhibition of AChE and hCAs. All compounds showed lower activity than reference drug acetazolamide (AAZ) for hCA I (Scheme 1a).…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Theoretical, in Silico and in Vitro Biological Evaluation Studies of New Thiosemicarbazones as Enzyme Inhibitors

Erdoğan,

Serdar Çavuş,

Muğlu

et al. 2023

Chemistry & Biodiversity

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Eleven new thiosemicarbazone derivatives (1‐11) were designed from nine different biologically and pharmacologically important isothiocyanate derivatives containing functional groups such as fluorine, chlorine, methoxy, methyl, and nitro at various positions of the phenyl ring, in addition to the benzyl unit in the molecular skeletal structure. First, their substituted‐thiosemicarbazide derivatives were synthesized from the treatment of isothiocyanate with hydrazine to synthesize the designed compounds. Through a one‐step easy synthesis and an eco‐friendly process, the designed compounds were synthesized with yields of up to 95% from the treatment of the thiosemicarbazides with aldehyde derivatives having methoxy and hydroxyl groups. The structures of the synthesized molecules were elucidated with elemental analysis and FT–IR, 1H NMR, and 13C NMR spectroscopic methods. The electronic and spectroscopic properties of the compounds were determined by the DFT calculations performed at the B3LYP/6‐311++G(2d,2p) level of theory, and the experimental findings were supported. They exhibited a highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (KI values are in the range of 23.54±4.34 to 185.90±26.16 nM, 103.90±23.49 to 325.90 ±77.99 nM, and 86.15±18.58 to 287.70±43.09 nM for AChE, hCA I, and hCA II, respectively). Furthermore, molecular docking simulations were performed to explain each enzyme‐ligand complex's interaction.

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis, Theoretical, in Silico and in Vitro Biological Evaluation Studies of New Thiosemicarbazones as Enzyme Inhibitors

Erdoğan,

Serdar Çavuş,

Muğlu

et al. 2023

Chemistry & Biodiversity

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“…Most naturally occurring toxins function as organic enzyme inhibitors. Synthetic enzyme inhibitors are employed as medications for treating various medical conditions. − Inhibitors are molecules capable of interfering with enzymatic activity by attaching to the enzyme’s active site either temporarily or permanently. They obstruct the enzyme’s active sites, thereby halting the enzymatic biological reaction .…”

Section: Introductionmentioning

confidence: 99%

Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure–Activity Relationship, Kinetics Mechanism, and In Silico Studies

Ahmad,

Abdul Qadir,

Ahmed

et al. 2023

ACS Omega

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Synthesis and Characterization of Novel 1,3‐Diaryltriazene‐Substituted Sulfaguanidine Derivatives as Selective Carbonic Anhydrase Inhibitors: Biological Evaluation, in Silico ADME/T and Molecular Docking Study

Akocak

Lolak

Duran

et al. 2023

Chemistry & Biodiversity

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Sulfonamide compounds known as human carbonic anhydrase (hCA) inhibitors are used in the treatment of many diseases such as epilepsy, antibacterial, glaucoma, various diseases. 1,3‐diaryl‐substituted triazenes and sulfaguanidine are used for therapeutic purposes in many drug structures. Based on these two groups, the synthesis of new compounds is important. In the present study, the novel 1,3‐diaryltriazene‐substituted sulfaguanidine derivatives (SG1‐13) were synthesized and fully characterized by spectroscopic and analytic methods. Inhibitory effect of these compounds on the hCA I and hCA II was screened as in vitro. All the series of synthesized compounds have been identified as potential hCA isoenzymes inhibitory with KI values in the range of 6.44±0.74‐86.85±7.01 nM for hCA I and with KI values in the range of 8.16±0.40‐77.29±9.56 nM for hCA II. Moreover, the new series of compounds showed a more effective inhibition effect than the acetazolamide used as a reference. The possible binding positions of the compounds with a binding affinity to the hCA I and hCA II was demonstrated by in silico studies. In conclusion, compounds with varying degrees of affinity for hCA isoenzymes have been designed and as selective hCA inhibitors. These compounds may be potential alternative agents that can be used to treat or prevent diseases associated with glaucoma and hCA inhibition.

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A novel series of thiosemicarbazone hybrid scaffolds: Design, synthesis, DFT studies, metabolic enzyme inhibition properties, and molecular docking calculations

Cited by 23 publications

References 118 publications

Synthesis, Theoretical, in Silico and in Vitro Biological Evaluation Studies of New Thiosemicarbazones as Enzyme Inhibitors

Synthesis, Theoretical, in Silico and in Vitro Biological Evaluation Studies of New Thiosemicarbazones as Enzyme Inhibitors

Exploring the Potential of New Benzamide-Acetamide Pharmacophore Containing Sulfonamide as Urease Inhibitors: Structure–Activity Relationship, Kinetics Mechanism, and In Silico Studies

Synthesis and Characterization of Novel 1,3‐Diaryltriazene‐Substituted Sulfaguanidine Derivatives as Selective Carbonic Anhydrase Inhibitors: Biological Evaluation, in Silico ADME/T and Molecular Docking Study

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