Novel chalcone derivatives of ursolic acid as acetylcholinesterase inhibitors: Synthesis, characterization, biological activity, ADME prediction, molecular docking and molecular dynamics studies

Journal of Molecular Structure, Год журнала: 2023, Номер 1295, С. 136804 - 136804

Опубликована: Окт. 7, 2023

Язык: Английский

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Novel quinazoline–chromene hybrids as anticancer agents: Synthesis, biological activity, molecular docking, dynamics and ADME studies

Archiv der Pharmazie, Год журнала: 2023, Номер 356(11)

Опубликована: Сен. 21, 2023

In this study, new quinazoline-chromene hybrid compounds were synthesized. The cytotoxic effects on cell viability of the tested against A549 human lung adenocarcinoma and BEAS-2B healthy bronchial epithelial lines in vitro. addition, ability active to inhibit migration was tested. Molecular docking studies performed evaluate ligand-protein interactions, molecular dynamics simulations determine interactions stability complexes. silico absorption, distribution, metabolism, excretion (ADME) conducted estimate drug-likeness compounds. Compounds 4 (IC50 = 51.2 µM) 5 44.2 found be most agents cells. They are more selective cells than reference drug doxorubicin. also have significantly migration. best scores epidermal growth factor receptor (EGFR) (-11.300 -11.226 kcal/mol) vascular endothelial 2 (VEGFR2) (-10.987 -11.247 kcal/mol), respectively. MD simulations, strong hydrogen bond above 80% simulation times showed a low ligand root mean square deviation (RMSD) around Å. According ADME analysis, exhibit excellent pharmacokinetic characteristics.

Язык: Английский

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Synthesis and Anticancer Activity of Novel Derivatives of α,β‐Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer Cells

Chemistry & Biodiversity, Год журнала: 2023, Номер 20(9)

Опубликована: Авг. 19, 2023

Abstract Herein, new derivatives of α , β‐ unsaturated ketones based on oleanolic acid ( 4 a – i ) were designed, synthesized, characterized, and tested against human prostate cancer (PC3). According to the in vitro cytotoxic study, title compounds showed significantly lower toxicity toward healthy cells (HUVEC) comparison with reference drug doxorubicin. The lowest IC 50 values PC3 cell lines b (7.785 μM), c (8.869 e (8.765 μM). results ADME calculations that drug‐likeness parameters within defined ranges according Lipinski's Jorgensen's rules. For most potent molecular docking analysis using induced fit (IFD) protocol was performed three protein targets (PARP, PI3K, mTOR). Based IFD scores, compound had highest calculated affinity for PARP1, while higher affinities mTOR PI3K. MM‐GBSA high binding formed stable complexes targets. Finally, ns dynamics simulation study behavior target under silico physiological conditions.

Язык: Английский

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

Chemistry & Biodiversity, Год журнала: 2023, Номер 20(8)

Опубликована: Июнь 29, 2023

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

Язык: Английский

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

ChemistrySelect, Год журнала: 2023, Номер 8(39)

Опубликована: Окт. 17, 2023

Abstract 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 tested against human colon cancer and umbilical vein endothelial cell lines. prospective inhibition mechanism, binding affinity complex stability molecular docking dynamics studies carried out on transforming growth factor beta‐2 (TGFβ2) vascular receptor 2 (VEGFR2) proteins. According to the biological (E)‐ 2,4‐dichloro‐N‐(2‐(2‐(4‐fluorobenzylidene)hydrazine‐1‐carbonyl)thiophen‐3‐yl)benzamide (11) was found as highest selective active compound. Anti‐cancer results compared reference drugs doxorubicin gefitinib. Most compound 7‐fold 4‐fold more than gefitinib, respectively. The detailed in vitro silico revealed that related demonstrated strong anti‐colon effect also it has promising inhibitory effects TGFβ2 VEGFR2. As a result, is candidate for further exploration development field treatment.

Язык: Английский

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4‐Furfuryloxymethyl‐1,2,3‐triazol‐1‐yl‐acetohydrazide Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors: Synthesis, Characterization and Comprehensive Biological Activity Studies

ChemistrySelect, Год журнала: 2024, Номер 9(6)

Опубликована: Фев. 6, 2024

Abstract This study focused on the synthesis and evaluation of biological activity ten novel acetohydrazide hybrid derivatives, having furfuryloxy‐1,2,3‐triazole ring. All target compounds were tested in vitro silico for their inhibitory potential against key enzymes: hAChE, hBChE, hCAI, hCAII, all involved significant physiological processes. Remarkably, two compounds, namely (E)‐2‐(4‐((furan‐2‐ylmethoxy)methyl)‐1H‐1,2,3‐triazol‐1‐yl)‐N′‐(4‐hydroxy‐3‐methoxybenzylidene)acetohydrazide (9) (E)‐N′‐(4‐chlorobenzylidene)‐2‐(4‐((furan‐2‐ylmethoxy)methyl)‐1H‐1,2,3‐triazol‐1‐yl)acetohydrazide (11) , exhibited strong activity. Compound 9 emerged as top‐performing inhibitor both hAChE (IC 50 0.23 μM) hBChE 0.74 μM). Additionally, 11 displayed potent effects hCAI with IC values 0.18 μM 0.15 μM, respectively. Furthermore, studies provided valuable insights into interaction mechanisms stability ligand‐protein complexes. demonstrated binding scores −12.063 kcal/mol −9.359 while substantial −7.040 −8.216 hCAII. In conclusion, they stand out promising inhibitors hCAII enzymes. Their activity, supported by low values, indicated to inhibit enzymes associated neurological metabolic

Язык: Английский

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Development of 1,2,3-triazole hybrids as multi-faced anticancer agents co-targeting EGFR/mTOR pathway and tubulin depolymerization

Bioorganic Chemistry, Год журнала: 2025, Номер 156, С. 108153 - 108153

Опубликована: Янв. 11, 2025

Язык: Английский

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Cytotoxic meroterpenoids from brown alga Stypopodium schimperi (Kützing) Verlaque & Boudouresque with comprehensive molecular docking & dynamics and ADME studies

Process Biochemistry, Год журнала: 2023, Номер 136, С. 90 - 108

Опубликована: Дек. 2, 2023

Язык: Английский

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Synthesis, Characterization, Molecular Docking and in vitro Biological Studies of Thiazolidin‐4‐one Derivatives as Anti‐Breast‐Cancer Agents

ChemistrySelect, Год журнала: 2023, Номер 8(20)

Опубликована: Май 24, 2023

Abstract In this study, 16 new compounds were synthesized starting from methylparaben. These consist of eight arylidenehydrazide derivatives and thiazolidin‐4‐on derivatives. All tested against MCF‐7 breast cancer cells MCF10A healthy tissue to determine their anti‐cancer activity. Molecular docking studies also carried out receptor proteins related the growth factor understand inhibition mechanism. According results, 4‐furan‐2‐ylmethoxy)‐N‐(4‐oxo‐2‐phenylthiazolidin‐3‐yl)benzamide ( 5 a ) 4‐(furan‐2‐ylmethoxy)‐N‐(2‐(4‐nitrophenyl)‐4‐oxothiazolidin‐3‐yl)benzamide e found as highest selective most active cells.

Язык: Английский

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Novel complex compounds of nickel with 3-(1-phenyl-2,3-dimethyl-pyrazolone-5)azopentadione-2,4: synthesis, NBO analysis, reactivity descriptors and in silico and in vitro anti-cancer and bioactivity studies

Journal of Biomolecular Structure and Dynamics, Год журнала: 2024, Номер unknown, С. 1 - 25

Опубликована: Янв. 31, 2024

A synthesized azo compound based on 4-amino antipyrine and its complexes with Ni(II) in solution solid phase is reported. The structures of these compounds have been testified by IR NMR spectroscopy. combined experimental theoretical approach was used. To study the structure properties compound, as well possible complex formation Ni(II), ab initio quantum-chemical calculations were carried out using Hartree-Fock (HF) method 6-31 G basis set electron density functional theory (DFT) hybrid three-parameter potential B3LYP extended 6-311++G(d,p) taking into account polarization diffuse functions for all atoms. geometric, energy, electronic parameters calculated analyzed. HOMO-LUMO energy gap has to determine chemical activity. Both had effective inhibition against butyrylcholinesterase acetylcholinesterase. IC50 values found 19.43 27.08 µM AChE, 2.37 7.40 BChE, respectively. For anticancer outcome, high doses E1 inhibited viability about 40–45%, while this rate around 65–70% E2 at same doses. Anticholinesterase also evaluated silico techniques. show strong binding VEGFR1, exhibiting superior inhibitory activity hAChE hBChE through shorter stronger interactions. MD simulations suggest that forms more stable compared E1, making it a promising candidate further exploration anticholinesterase therapies.

Язык: Английский

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