Design, synthesis, anticancer activity of new amide derivatives derived from 1,2,3-triazole-benzofuran hybrids: An insights from molecular docking, molecular dynamics simulation and DFT studies

Gariganti, Naganjaneyulu; Loke, Shiva Krishna; Pagadala, Eswar; Chinta, Poojitha; Poola, Bhaskar; Chetti, Prabhakar; Bansal, Arubhi; Ramachandran, Balajee; Srinivasadesikan, Venkatesan; Kottalanka, Ravi K.

doi:10.1016/j.molstruc.2022.134250

Cited by 22 publications

(12 citation statements)

References 78 publications

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“…The simulation was run, with a time step of 2.5 fs and using the RESPA integrator. The interactions between the ligand and protein during the binding were analyzed, as well as the root mean square deviation (RMSD) of the Cα atoms of the protein and the heavy atoms of the ligand, by utilizing Desmond [53] …”

Section: Methodsmentioning

confidence: 99%

Synthesis and Evaluation of Quinazolin‐4(3H)‐one Derivatives as Multitarget Metabolic Enzyme Inhibitors: A Biochemistry‐Oriented Drug Design

Tokalı¹,

Taslimi²,

Sadeghi

et al. 2023

ChemistrySelect

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In this study, imines bearing quinazolin‐4(3H)‐one were synthesized and their inhibitory properties were investigated against some metabolic enzymes including Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), α‐Glycosidase (α‐Gly), and human Carbonic Anhydrase I–II (hCA I–II). All compounds had inhibitory strength with Ki values in the range of 38.55±4.08–159.05±10.68 nM and 41.04±6.73–177.12±8.06 nM against hCA I and hCA‐II, respectively in comparison to the standard acetazolamide (AZA) Ki=125.15±0.78 nM (for hCA‐I) and Ki=148.75±0.92 nM (for hCA‐II). The compounds showed potent inhibitory activity against α‐Gly enzyme with IC50 value 0.34–2.28 nM (standard inhibitor acarbose (ACR): 3.18 nM). Also, these analogs had potent inhibitory strength with Ki values in the range of 4.20±0.15–26.10±2.36 nM against AChE and 1.22±0.05–16.09±0.88 nM against BChE in comparison to the standard tacrine (TAC) Ki=37.62±6.86 nM (for AChE) and Ki=26.75±5.79 nM (for BChE). Additionally, the molecular docking and molecular dynamics simulation study was carried out for the determination of ligand‐enzyme interactions. The docking scores of the most active compound were calculated as −7.31, −7.59, −6.66, −6.93 and −7.11 kcal/mol for AChE, BChE, hCA I, hCA II, and α‐Gly, respectively.

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Section: Methodsmentioning

confidence: 99%

Synthesis and Evaluation of Quinazolin‐4(3H)‐one Derivatives as Multitarget Metabolic Enzyme Inhibitors: A Biochemistry‐Oriented Drug Design

Tokalı¹,

Taslimi²,

Sadeghi

et al. 2023

ChemistrySelect

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show abstract

“…The simulation was run, with a time step of 2.5 fs and using the RESPA integrator. The interactions between the ligand and protein during the binding were analyzed, as well as the RMSD, of the Cα atoms of the protein and the heavy atoms of the ligand, by utilizing Desmond [52,53] …”

Section: Methodsmentioning

confidence: 99%

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

Şenol

Cagman

Katmerlikaya

et al. 2023

Chemistry & Biodiversity

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In this study, twenty new anthranilic acid hydrazones 6–9 (a–e) were synthesized and their structures were characterized by Fourier‐transform Infrared (FT‐IR), Nuclear Magnetic Resonance (1H‐NMR – 13C‐NMR), and High‐resolution Mass Spectroscopy (HR‐MS). The inhibitory effects of the compounds against COX‐II were evaluated. IC50 values of the compounds were found in the range of >200–0.32 μM and compounds 6e, 8d, 8e, 9b, 9c, and 9e were determined to be the most effective inhibitors. Cytotoxic effects of the most potent compounds were investigated against human hepatoblastoma (Hep‐G2) and human healthy embryonic kidney (Hek‐293) cell lines. Doxorubicin (IC50: 8.68±0.16 μM for Hep‐G2, 55.29±0.56 μM for Hek‐293) was used as standard. 8e is the most active compound, with low IC50 against Hep‐G2 (4.80±0.04 μM), high against Hek‐293 (159.30±3.12), and high selectivity (33.15). Finally, molecular docking and dynamics studies were performed to understand ligand‐protein interactions between the most potent compounds and COX II, Epidermal Growth Factor Receptor (EGFR), and Transforming Growth Factor beta II (TGF‐βII). The docking scores were calculated in the range of −10.609–−6.705 kcal/mol for COX‐II, −8.652–−7.743 kcal/mol for EGFR, and −10.708–−8.596 kcal/mol for TGF‐βII.

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“…The simulation was run, with a time step of 2.5 ps and using the RESPA integrator. The interactions between the ligand and protein during the binding were analyzed, as well as the RMSD, of the Cα atoms of the protein and the heavy atoms of the ligand, by utilizing Desmond [35–38] …”

Section: Methodsmentioning

confidence: 99%

“…The interactions between the ligand and protein during the binding were analyzed, as well as the RMSD, of the Cα atoms of the protein and the heavy atoms of the ligand, by utilizing Desmond. [35][36][37][38]…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

3‐Amino‐thiophene‐2‐carbohydrazide Derivatives as Anti Colon Cancer Agents: Synthesis, Characterization, In‐Silico and In‐Vitro Biological Activity Studies

Şenol,

Çakır

2023

ChemistrySelect

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In this study, starting from 3‐amino‐thiophene‐2‐carboxylic acid methyl ester, eighteen new arylidenehydrazide derivatives (4–21) were synthesized. To determine cytotoxic activity of target compounds they were tested against human colon cancer and human umbilical vein endothelial cell lines. To determine prospective inhibition mechanism, binding affinity and complex stability molecular docking and molecular dynamics studies were carried out on transforming growth factor beta‐2 (TGFβ2) and vascular endothelial growth factor receptor 2 (VEGFR2) proteins. According to the biological activity studies compounds (E)‐2,4‐dichloro‐N‐(2‐(2‐(4‐fluorobenzylidene)hydrazine‐1‐carbonyl)thiophen‐3‐yl)benzamide (11) was found as the highest selective and active compound. Anti‐cancer activity results compared to reference drugs doxorubicin and gefitinib. Most active compound was found as 7‐fold and 4‐fold more selective than doxorubicin and gefitinib, respectively. The detailed in vitro and in silico biological activity studies revealed that related compound demonstrated strong and selective anti‐colon cancer effect and also it has promising inhibitory effects on TGFβ2 and VEGFR2. As a result, this compound is a promising candidate for further exploration and development in the field of colon cancer treatment.

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Design, synthesis, anticancer activity of new amide derivatives derived from 1,2,3-triazole-benzofuran hybrids: An insights from molecular docking, molecular dynamics simulation and DFT studies

Cited by 22 publications

References 78 publications

Synthesis and Evaluation of Quinazolin‐4(3H)‐one Derivatives as Multitarget Metabolic Enzyme Inhibitors: A Biochemistry‐Oriented Drug Design

Synthesis and Evaluation of Quinazolin‐4(3H)‐one Derivatives as Multitarget Metabolic Enzyme Inhibitors: A Biochemistry‐Oriented Drug Design

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

3‐Amino‐thiophene‐2‐carbohydrazide Derivatives as Anti Colon Cancer Agents: Synthesis, Characterization, In‐Silico and In‐Vitro Biological Activity Studies

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