Investigating Novel Thiophene Carbaldehyde Based Thiazole Derivatives as Potential Hits for Diabetic Management: Synthesis, In Vitro and In Silico Approach

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(8)

Published: Feb. 21, 2024

Abstract This research work is based on synthesis of eleven novel thiazole derivatives (3 a‐k) thiophene carbaldehyde. All the synthesized compounds were successfully synthesized, characterized by 1 H‐NMR and EI‐MS spectroscopic techniques finally subjected for their in vitro α‐glucosidase inhibitory activity. Seven 3 i (IC 50 =10.21±1.84 μM) , b =11.14±0.99 f =13.21±2.76 h =14.21±0.31 k =15.21±1.02 e =16.21±1.32 μM), c =18.21±1.89 series displayed excellent potential better than standard acarbose. However, two g =33.21±1.99 d =42.31±2.12 showed significant activity while j a found less active with IC values 82.31±0.31 88.36±1.21 μM respectively. Additional revealed that are not exhibiting any cytotoxic effects. The molecular docking study these good binding site interactions scores.

Language: Английский

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Insights into antimicrobial potential of functionalized thiazoles: In vitro and in silico analysis

Journal of Molecular Liquids, Journal Year: 2025, Volume and Issue: unknown, P. 127064 - 127064

Published: Feb. 1, 2025

Language: Английский

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Synthesis of New Thiazole-Privileged Chalcones as Tubulin Polymerization Inhibitors with Potential Anticancer Activities

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(9), P. 1154 - 1154

Published: Aug. 31, 2024

A series of novel thiazole-based chalcones were evaluated for their anticancer activity as potential tubulin polymerization inhibitors. In vitro screening the thiazole derivatives

Language: Английский

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Synthesis, antifungal activity, and molecular simulation study of nootkatone‐based thiazole‐hydrazone compounds as novel succinate dehydrogenase inhibitor

Pest Management Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Plant diseases cause huge losses in agriculture worldwide every year, but the prolonged use of current commercial fungicides has led to development resistance plant pathogenic fungi. Therefore, there is an urgent need develop new, efficient, and green fungicides. Twenty-three nootkatone-based thiazole-hydrazone compounds were designed, synthesized, characterized by Fourier-transform infrared (FTIR), proton (1H) nuclear magnetic resonance (NMR), carbon-13 (13C) NMR, high-resolution mass spectrometry (HRMS). The antifungal activities results showed that all target displayed certain activity against eight tested Among them, 3a (88.7%), 3b (92.5%), 3d 3f (84.9%), 3j 3l (92.5%) comparable or superior positive control boscalid (88.7%) their inhibitory Physalospora piricola. Meanwhile, compound had half maximal effective concentration (EC50) values 18.0172, 18.8236, 16.5914, 18.5044, 16.5660 μg/mL Fusarium oxysporum f. sp. cucumerinum, Alternaria solani, Gibberella zeae, Bipolaris maydis, Colleterichum orbicalare, respectively, exhibiting outstanding broad-spectrum fungicidal activity. Moreover, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was carried out investigate between molecular structures 3a-3w Furthermore, [half (IC50) = 4.936 μmol/L] significantly better succinate dehydrogenase (SDH) than (IC50 6.631 μmol/L). possible binding mode homology-modeling built SDH, also explored docking. Target deserved further as promising candidate for novel SDH inhibitor. © 2025 Society Chemical Industry.

Language: Английский

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Synthesis of New Thiazole‐Pyrazole Analogues: Molecular Modelling, Antiproliferative/Antiviral Activities, and ADME Studies

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(3)

Published: March 1, 2025

ABSTRACT Twelve thiazole‐pyrazole analogues 4 , 6 and 8 were synthesized by introducing various pyrazole systems into the core, 2‐((4‐acetylphenyl)amino)‐4‐methylthiazole ( 2 ), through many synthetic approaches. The density functional theory (DFT) study of revealed coincided configurations their highest occupied lowest unoccupied molecular orbitals (HOMO LUMO), except for nitro derivatives, in which intramolecular charge‐transfer (CT) may be denoted as π → π* n π*. In addition, vitro antiproliferative efficacy towards some cancer cell lines was examined (Panc‐1, HT‐29, MCF‐7) non‐cancerous (WI‐38), using Dasatinib (Reference). 4c 4d demonstrated most potent anticancer effect, particularly against Panc‐1 MCF‐7 cells. Moreover, antiviral activity H5N1, a plaque reduction assay, showed that analogue 6a exhibited (100% inhibition TC 50 = 61 μg/μL), comparable to reference drug amantadine (TC 72 μg/μL, 100% inhibition). Furthermore, docking disclosed range interactions, such H‐bonding π‐π stacking, with binding affinities between −4.8558 − 8.3673 kcal/mol. Additionally, SwissADME predictions indicated possess promising drug‐like characteristics, but 4a–d 8c inadequate solubility bioavailability, restricts use viable oral medications.

Language: Английский

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Design, synthesis, in silico studies, and apoptotic antiproliferative activity of novel thiazole-2-acetamide derivatives as tubulin polymerization inhibitors

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: April 16, 2025

Introduction Tubulin polymerization inhibitors have emerged as interesting anticancer therapies. We present the design, synthesis, and structural elucidation of novel thiazole-based derivatives to identify tubulin with potent antiproliferative efficacy strong inhibition polymerization. Methods The compounds consist two scaffolds. Scaffold A 10a-e scaffold B 13a-e . structures newly synthesized were validated using 1 H NMR, 13 C elemental analysis. Results Discussion most effective antitubulin derivative was 10a , exhibiting an IC 50 value 2.69 μM. Subsequently, 10o 13d exhibited values 3.62 μM 3.68 μM, respectively. These more potency than reference combretastatin A-4, which displayed 8.33 had no cytotoxic effects on normal cells, preserving over 85% cell viability at experiment demonstrated that significant activity against four cancer lines, average GI 6, 7, 8 equivalent reference’s doxorubicin sorafenib. Compounds 10a, 10o, activate caspases 3, 9, Bax, while down-regulating anti-apoptotic protein Bcl2. Molecular docking studies superior binding affinities for (-7.3 kcal/mol) colchicine site tubulin, forming key hydrophobic hydrogen bonding interactions enhance its activity. ADMET analysis confirmed favorable drug-like properties, establishing these promising candidates further development agents targeting

Language: Английский

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Synthesis, biological evaluation, and computational studies of thiazolyl hydrazone derivatives as triple mutant allosteric EGFR inhibitors

Journal of the Chinese Chemical Society, Journal Year: 2024, Volume and Issue: 71(7), P. 706 - 720

Published: June 11, 2024

Abstract Herein, new thiazole‐2‐yl‐based hydrazone derivatives were synthesized and assessed for in vitro anticancer activity against wild type A549, MCF7, DU145, mutant H1975 cancer cell lines by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Among all, 4‐(4‐Chlorophenyl)‐2‐(2‐((4‐methylthiazol‐5‐yl)methylene)hydrazineyl)thiazole ( 4b ) elicited prominent wild‐type epidermal growth factor receptor (WT‐EGFR) MCF7 line with an IC 50 value of 9.57 ± 1.80 μM, whereas 4‐Methyl‐5‐((2‐(4‐(4‐nitrophenyl)thiazol‐2‐yl)hydrazineylidene)methyl)thiazole 4c showed appreciable 11 0.7 μM the mutated EGFR lung cells. Doxorubicin Osimertinib used as standard drugs comparison activity. Compound significantly increased early apoptosis (30.2%) late (7.6%) at a 5 concentration control (early 2.5%, 1.2%). The molecular docking study was performed (T790M/C797S) PDB: 5D41 enzyme to gain information about interactions molecules binding pockets. Moreover, ADME dynamic simulation studies accomplished insight into drug‐likeness conformational stability, respectively. findings demonstrate promising alignment between observed effects computational analyses.

Language: Английский

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Exploring a novel thiazole derivatives hybrid with fluorinated-indenoquinoxaline as dual inhibitors targeting VEGFR2/AKT and apoptosis inducers against hepatocellular carcinoma with docking simulation

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 154, P. 108023 - 108023

Published: Dec. 2, 2024

Language: Английский

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Novel hydroxy-tagged bis-dihydrazothiazole derivatives: Synthesis, antimicrobial capacity and formation of some metal chelates with iron, cobalt and zinc ions

Arabian Journal of Chemistry, Journal Year: 2024, Volume and Issue: 17(9), P. 105933 - 105933

Published: July 24, 2024

Until today, microbial infections epitomize a serious universal health threat. Subsequently, developing potential antimicrobial prototype remains an urgent, global necessity. Despite several reports discussing the biological utility of some bis-thiazoles, use bis-dihydrazothiazoles and their corresponding metal chelates as potent antimicrobials, is yet to be explored. The current report outlines attempt fill that void by representing successful synthesis new class well three transition antimicrobials. This presents design novel hydroxy-tagged 6a-e bis-dihydrazothiazolones 9a-e via reaction bis-aldehyde thiosemicarbazone 3, common synthetic precursor, with two groups hydrazonoyl halide derivatives 4a-e 7a-e. chelation affinity these behave neutral tridentate ligands coordinating ions; Fe(III), Co(II), or Zn(II) through azomethine-N, thiazole-S, azo-N atoms form complexes metal/ligand ratio 2:1 was confirmed. In-vitro, screening bis-dihydrazothiazole derivatives, selected group chelate [M2L], inspected, data were measured in comparison those ketoconazole gentamycin reference standards. Most showed decent excellent activities against screened microbes, but chloro-substituted bis dihydrazothiazole 6c 9c exceptional inhibition Bacillus subtilis (20 mm), Escherichia coli (25 Candida albicans (19 Salmonella typhimurium respectively. Additionally, amongst synthesized only zinc complex, [Zn2L] remarkable both Staphylococcus aureus (21 mm) compared standard Gentamycin, more than free ligand, 6a itself (no activity 11 mm respectively). Antimicrobial inspection assessed agar diffusion assay method all bacterial fungal strains. Magnetic moment, diffused reflectance, FT-IR, 1H NMR, molar conductivity, thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscope (SEM) among many techniques used elucidate structures bis-heterocyclic complexes.

Language: Английский

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1,4-Naphthoquinone thiazoles: Synthesis, crystal structure, anti-proliferative activity, and inverse molecular docking study

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1322, P. 140330 - 140330

Published: Oct. 9, 2024

Language: Английский

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