Novel coumarin-chalcone derivatives: Synthesis, characterization, antioxidant, cyclic voltammetry, molecular modelling and biological evaluation studies as acetylcholinesterase, α-glycosidase, and carbonic anhydrase inhibitors

Çelik Onar, Hülya; Özden, Eda Mehtap; Taslak, Hava Dudu; Gülçin, İlhami; Ece, Abdulilah; Erçağ, Erol

doi:10.1016/j.cbi.2023.110655

Cited by 7 publications

(3 citation statements)

References 47 publications

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“…A multitarget approach was also chosen by Onar et al for the design of new AD drugs ( Çelik Onar et al, 2023 ). Twelve coumarin-chalcone derivatives were synthesized, and their biological activity was evaluated against AChE, human carbonic anhydrases (hCAs) I and II, and α–glycosidase (α-Gly).…”

Section: Biological Applications Of Coumarin Derivativesmentioning

confidence: 99%

Syntheses, reactivity, and biological applications of coumarins

Citarella,

Vittorio,

Dank

et al. 2024

Front. Chem.

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This comprehensive review, covering 2021–2023, explores the multifaceted chemical and pharmacological potential of coumarins, emphasizing their significance as versatile natural derivatives in medicinal chemistry. The synthesis and functionalization of coumarins have advanced with innovative strategies. This enabled the incorporation of diverse functional fragments or the construction of supplementary cyclic architectures, thereby the biological and physico-chemical properties of the compounds obtained were enhanced. The unique chemical structure of coumarine facilitates binding to various targets through hydrophobic interactions pi-stacking, hydrogen bonding, and dipole-dipole interactions. Therefore, this important scaffold exhibits promising applications in uncountable fields of medicinal chemistry (e.g., neurodegenerative diseases, cancer, inflammation).

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Section: Biological Applications Of Coumarin Derivativesmentioning

confidence: 99%

Syntheses, reactivity, and biological applications of coumarins

Citarella,

Vittorio,

Dank

et al. 2024

Front. Chem.

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“…MD simulations help us to study dynamics of ligand-protein complexes to elucidate binding interactions and the conformational changes of both protein and the ligands in a biologically simulated environment [42][43][44]. Three complexes (compounds 256, 322, and 489 docked complexes) were subjected to MD simulations to evaluate the stability of macromolecules and also to reveal critical binding interactions throughout the simulations.…”

Section: Simulationsmentioning

confidence: 99%

Structural Characterization of TRAF6 N-Terminal for Therapeutic Uses and Computational Studies on New Derivatives

Guven,

Sever,

Başoğlu-Ünal

et al. 2023

Pharmaceuticals

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Tumor necrosis factor receptor-associated factors (TRAFs) are a protein family with a wide variety of roles and binding partners. Among them, TRAF6, a ubiquitin ligase, possesses unique receptor binding specificity and shows diverse functions in immune system regulation, cellular signaling, central nervous system, and tumor formation. TRAF6 consists of an N-terminal Really Interesting New Gene (RING) domain, multiple zinc fingers, and a C-terminal TRAF domain. TRAF6 is an important therapeutic target for various disorders and structural studies of this protein are crucial for the development of next-generation therapeutics. Here, we presented a TRAF6 N-terminal structure determined at the Turkish light source “Turkish DeLight” to be 3.2 Å resolution at cryogenic temperature (PDB ID: 8HZ2). This structure offers insight into the domain organization and zinc-binding, which are critical for protein function. Since the RING domain and the zinc fingers are key targets for TRAF6 therapeutics, structural insights are crucial for future research. Separately, we rationally designed numerous new compounds and performed molecular docking studies using this template (PDB ID:8HZ2). According to the results, 10 new compounds formed key interactions with essential residues and zinc ion in the N-terminal region of TRAF6. Molecular dynamic (MD) simulations were performed for 300 ns to evaluate the stability of three docked complexes (compounds 256, 322, and 489). Compounds 256 and 489 was found to possess favorable bindings with TRAF6. These new compounds also showed moderate to good pharmacokinetic profiles, making them potential future drug candidates as TRAF6 inhibitors.

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“…For α-glycosidase, the chalconeÀ coumarin derivative containing phenyl groups has the best inhibition value, including acarbose. [21] Amin et al, tested a variety of natural and synthetic coumarins, including thiosemicarbazone derivatives, as acetylcholinesterase (AChE) inhibitors. They used donepezil as a reference compound and discussed the structure-activity relationships of the coumarins.…”

Section: Introductionmentioning

confidence: 99%

New Coumarin−Thiosemicarbazone Based Zn(II), Ni(II) and Co(II) Metal Complexes: Investigation of Cholinesterase, α‐Amylase, and α‐Glucosidase Enzyme Activities, and Molecular Docking Studies

Çelik,

Özdemir,

Köksoy

et al. 2023

ChemistrySelect

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New coumarin−thiosemicarbazone compounds and their zinc(II), nickel(II), and copper(II) metal complexes were synthesized and characterized. The inhibitory activities of these new coumarin−thiosemicarbazone‐based metal complexes against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), α‐amylase, and α‐glucosidase were determined. The results showed that all the synthetic compounds exhibited potent inhibitory activities against all targets, as compared to the standard inhibitors, as revealed by the half‐maximal inhibitory concentration (IC50) and the inhibitory constant (Ki) values. The Ki values of the new complexes for BChE, AChE, and α‐glucosidase enzymes were obtained in the ranges of 115.84–276.07, 31.68–117.08, and 22.56–47.82 μM, respectively. Moreover, molecular docking studies provided support for the conclusion that coumarin−thiosemicarbazone zinc(II) (−102.34; −10.41 kcal/mol) and coumarin−thiosemicarbazone cobalt(II) complexes (−25.46; −9.49 kcal/mol) act as dual inhibitors for both AChE and α‐amylase species. Furthermore, coumarin−thiosemicarbazone cobalt(II) (−39.46 kcal/mol) and coumarin−thiosemicarbazone nickel(II) complexes (−39.41 kcal/mol) demonstrated potential as inhibitors of α‐glucosidase. Of all the compounds studied, bis‐3‐benzyl‐7,8‐dimethoxycoumarin−thiosemicarbazonato zinc(II) is the most potent drug against AChE.

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Novel coumarin-chalcone derivatives: Synthesis, characterization, antioxidant, cyclic voltammetry, molecular modelling and biological evaluation studies as acetylcholinesterase, α-glycosidase, and carbonic anhydrase inhibitors

Cited by 7 publications

References 47 publications

Syntheses, reactivity, and biological applications of coumarins

Syntheses, reactivity, and biological applications of coumarins

Structural Characterization of TRAF6 N-Terminal for Therapeutic Uses and Computational Studies on New Derivatives

New Coumarin−Thiosemicarbazone Based Zn(II), Ni(II) and Co(II) Metal Complexes: Investigation of Cholinesterase, α‐Amylase, and α‐Glucosidase Enzyme Activities, and Molecular Docking Studies

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