Design, synthesis, molecular docking, biological evaluations and QSAR studies of novel dichloroacetate analogues as anticancer agent

Fereidoonnezhad, Masood; Tabaei, Samira; Sakhteman, Amirhossein; Seradj, Hassan; Faghih, Zeinab; Faghih, Zahra; Mojaddami, Ayyub; Sadeghian, Batool; Rezaei, Zahra

doi:10.1016/j.molstruc.2020.128689

Cited by 22 publications

(32 citation statements)

References 27 publications

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“…The three‐dimensional crystal structure of the HK II (PDB ID: 2NTZ) enzyme was obtained from the protein data bank (http://www.rcsb.org/pdb). After removing water molecules and co‐crystal ligand (3‐BP), the enzyme was converted to PDBQT, and gasteiger partial charges were added using MGLTools 1.5.6 [44,45] . The structure of each ligand was drawn by the ChemBioDraw (version 12.0) and optimized using Hyperchem (Version 8, Hypercube Inc., Gainesville, FL, USA) software.…”

Section: Methodsmentioning

confidence: 99%

“…After removing water molecules and co-crystal ligand (3-BP), the enzyme was converted to PDBQT, and gasteiger partial charges were added using MGLTools 1.5.6. [44,45] The structure of each ligand was drawn by the ChemBioDraw (version 12.0) and optimized using Hyperchem (Version 8, Hypercube Inc., Gainesville, FL, USA) software. During the optimization procedure, the molecular mechanics (MM +) method and then the quantumbased semiempirical method (AM1) were utilized.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

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Novel Hydrazone Derivatives of 3‐Bromopyruvate: Synthesis, Evaluation of the Cytotoxic Effects, Molecular Docking and ADME Studies

Beygi

Mostoufi

Mojaddami

2022

Chemistry & Biodiversity

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A series of 3‐bromopyruvate (3‐BP) derivatives were synthesized to develop new potent anticancer agents. The chemical structures of the compounds were characterized using FT‐IR, 1H‐, 13C‐NMR spectroscopy, and elemental analysis (CHN). Their cytotoxic activities were investigated against four cancer cell lines, including colon (SW1116), breast (MDA‐MB‐231), lung (A549), and liver (HepG2) cancer cell lines. Among the synthesized compounds, 3b showed promising cytotoxic activity compared to 3‐BP, with IC50 values of 16.3 μM, 19.1 μM, 27.8 μM, and 14.5 μM against A549, MDA‐MB‐231, SW1116 and, HepG2 cell lines, respectively. Furthermore, the effect of these compounds on MCF‐10A (a normal breast cell lines) was investigated to determine their selectivity between tumorigenic and non‐tumorigenic cells. Since the 3‐BP inhibits hexokinase II (HK II), molecular docking of 3‐BP derivatives was carried out using AutoDock 4.2. The binding energies of these derivatives were greater than 3‐BP, indicating that they had a higher affinity for HK II. For validation of docking, a 40 ns MD simulation was performed. SwissADME was used to predict pharmacokinetics, drug‐likeness, and ADME parameters of the screened compounds. The results demonstrated that these derivatives are suitable candidates for developing orally potent HK II inhibitors.

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Section: Methodsmentioning

confidence: 99%

Section: Molecular Docking Studiesmentioning

confidence: 99%

Novel Hydrazone Derivatives of 3‐Bromopyruvate: Synthesis, Evaluation of the Cytotoxic Effects, Molecular Docking and ADME Studies

Beygi

Mostoufi

Mojaddami

2022

Chemistry & Biodiversity

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“…Frondosins C was also showed this type of interaction by hydrogen bonding. Some hydrophobic interactions, with LEU112A and ILE96A residues, were also observed for co-crystalline ligand and Frondosins C. The obtained RMSD values was 0.79 Å. RMSD value less than 2 Å indicating validated docking protocol [23][24][25].…”

Section: Dockingmentioning

confidence: 99%

“…The value for the surface below the chart of ROC curve for active ligands and 110 inactive ligands on IL-17A is 0.853 ( Figure 3). The value for the surface below the chart between 0.8 and 0.9 is considered good and reasonable, and values between 0.7 and 0.8 are acceptable [29][30].…”

Section: Analysis Of Receiver Operating Characteristics (Roc)mentioning

confidence: 99%

Molecular docking and druggability studies of terpenoid-derived metabolites from marine sponges as IL-17A inhibitors

2019

Eurasian Chem. Commun.

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In this study, physicochemical properties of 49 compounds, extracted from antiinflammatory sponge species with the aim of ADMET test and Lipinski rule of five, have been determined. Fourteen compounds, which showed the best results, were subjected to molecular docking studies with IL-17. Among these compounds, four compounds with low binding energy were obtained. These compounds; namely, frondosins C, frondosins D, methylpourewate B, and Cadlinolide C, have shown promising ADMET properties and strong interactions in the active site of IL-17. The ROC curve with the acceptable area under the curve of 0.853 was used for validation of the docking protocol. If the efficacy of these compounds is proven by biochemical tests, the molecules will be potentially important inhibitors of IL-17A and used as a basis for the further development of anti-inflammatory and anti-psoriasis agents.

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“…Extensive QSAR (quantitative structure-activity relationships) and molecular docking studies have been conducted on a series of N-aryldichloroacetamide and aryl dichloroacetate derivatives using PDKs isoenzymes, which suggested that a number of hydrogen bond acceptor interactions exist between the oxygen of amidic carbonyl group and different amino acid residues in various PDKs [14]. Molecular docking studies using honokiol bis-dichloroacetate and TNF receptor-associated protein 1 (TRAP1) showed important contacts between the ligand and the protein residues in the allosteric pocket, and as a result, honokiol bis-dichloroacetate could act as a selective allosteric inhibitor of the mitochondrial chaperone TRAP1 [15].…”

Section: Introductionmentioning

confidence: 99%

Dichloroacetyl Amides of 3,5-Bis(benzylidene)-4-piperidones Displaying Greater Toxicity to Neoplasms than to Non-Malignant Cells

et al. 2022

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A series of 3,5-bis(benzylidene)-1-dichloroacetyl-4-piperidones 1a–l was evaluated against Ca9-22, HSC-2, HSC-3, and HSC-4 squamous cell carcinomas. Virtually all of the compounds displayed potent cytotoxicity, with 83% of the CC50 values being submicromolar and several CC50 values being in the double digit nanomolar range. The compounds were appreciably less toxic to human HGF, HPLF, and HPC non-malignant cells, which led to some noteworthy selectivity index (SI) figures. From these studies, 1d,g,k emerged as the lead molecules in terms of their potencies and SI values. A Quantitative Structure-Activity Relationship (QSAR) study revealed that cytotoxic potencies and potency–selectivity expression figures increased when the magnitude of the sigma values in the aryl rings was elevated. The modes of action of the representative cytotoxins in Ca9-22 cells were found to include G2/M arrest and stimulation of the cells to undergo mitosis and cause poly(ADP-ribose) polymerase (PARP) and procaspase 3 cleavage.

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Design, synthesis, molecular docking, biological evaluations and QSAR studies of novel dichloroacetate analogues as anticancer agent

Cited by 22 publications

References 27 publications

Novel Hydrazone Derivatives of 3‐Bromopyruvate: Synthesis, Evaluation of the Cytotoxic Effects, Molecular Docking and ADME Studies

Novel Hydrazone Derivatives of 3‐Bromopyruvate: Synthesis, Evaluation of the Cytotoxic Effects, Molecular Docking and ADME Studies

Molecular docking and druggability studies of terpenoid-derived metabolites from marine sponges as IL-17A inhibitors

Dichloroacetyl Amides of 3,5-Bis(benzylidene)-4-piperidones Displaying Greater Toxicity to Neoplasms than to Non-Malignant Cells

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