Poly (ADP-ribose) polymerase (PARP) inhibitors as anticancer agents: An outlook on clinical progress, synthetic strategies, biological activity, and structure-activity relationship

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 274, P. 116535 - 116535

Published: May 31, 2024

Language: Английский

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Therapeutic potential of anticancer activity of nitrogen-containing heterocyclic scaffolds as Janus kinase (JAK) inhibitor: Biological activity, selectivity, and structure–activity relationship

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 152, P. 107696 - 107696

Published: Aug. 8, 2024

Language: Английский

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Benzothiazole a privileged scaffold for Cutting-Edges anticancer agents: Exploring drug design, structure-activity relationship, and docking studies

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 279, P. 116831 - 116831

Published: Sept. 6, 2024

Language: Английский

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Design, synthesis, and biological evaluation of novel 4-(4-ethoxyphenyl)-6-(substituted-phenyl)pyrimidin-2-amine/thiol/hydroxy derivatives as EGFRWT and EGFRT790M inhibitors targeting NSCLC: In-vitro and in-silico exploration

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: 1327, P. 141227 - 141227

Published: Jan. 2, 2025

Language: Английский

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Synthetic product-based approach toward potential antileishmanial drug development

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 263, P. 115927 - 115927

Published: Nov. 11, 2023

Language: Английский

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Pyrazole, Pyrazoline, and Fused Pyrazole Derivatives: New Horizons in EGFR‐Targeted Anticancer Agents

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: 21(11)

Published: July 26, 2024

Pyrazole and its derivatives remain popular heterocycles in drug research, design, development. Several drugs include the pyrazole scaffold, such as ramifenazone, ibipinabant, antipyrine, axitinib, etc. They have been extensively studied by scientific community are said to a wide range of biological activity, especially anticancer agents targeting EGFR. Overexpression EGFR signalling promotes tumor growth inhibiting apoptosis. dysfunction has described multiple cancers, including colon, head neck, NSCLC, liver, breast, ovarian cancer. As result, represents prospective target for cancer treatment. anti-EGFR thriving, notably dacomitinib, afatinib, erlotinib, gefitinib, osimertinib. However, almost all currently available limited therapeutic effectiveness due lack selectivity well substantial side effects. Furthermore, aberrant across numerous human malignancies/carcinomas is impeded gene amplification, protein overexpression, mutations, or in-frame deletions, making EGFR-induced treatment challenging. To overcome such, novel with high efficacy minimal toxicity required. battle resistance inhibitors, pyrazole, pyrazoline, their investigated viable pharmacophore development new better potency, lesser toxicity, favourable pharmacokinetic characteristics. The present investigation covers examination progress toward anti-cancer therapies via fused pyrazole-based compounds. current study also inclusive data on marketed candidates undergoing preclinical clinical Lastly, we discussed recent advances medicinal chemistry significance eradication various cancers provide direction structure-activity relationship (SAR), mechanistic studies.

Language: Английский

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Advancement of DDR1 and DDR2 Inhibitors: Therapeutic Potential of Bioactive Compounds, Designing Strategies, and Structure‐Activity Relationship (SAR)

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(30)

Published: Aug. 6, 2024

Abstract DDR1 and DDR2 are nonintegrin collagen receptors in the receptor tyrosine kinase family. Both DDRs bind to various types perform crucial functions embryo development. different from other kinases due their interaction with extracellular matrix components unusual activation kinetics. DDR regulates cell migration, survival, proliferation, differentiation, remodeling. Dysregulated function is linked advancement of several human illnesses, including fibrosis, arthritis, neurodegenerative diseases, cancer. play a vital role disease progression Therefore, use inhibitors represents promising therapeutic strategy, particularly for disorders limited therapy alternatives. In recent years, have been regarded as attractive targets drug development, evidenced by significant rise research this field. The current review illustrates about small molecules, designing strategies structure‐activity relationship. can contain core structures such pyrimidine, phthalazine, pyrazole, pyrazine, imidazo[1,2‐ ]sspyrazine, quinazoline, thieno[3,2‐ b ]pyridin‐7‐yl derivatives. Furthermore, based on constructive analysis published derivatives, we found that majority powerful compounds similar scaffold (amide linker, hydrophobic tail, hinge binder or without spacer). Among literature, most potent 4 ( ]pyrazine ) , 5 (pyridine), 19 24 (quinazoline) displayed activity against IC 50 values ranging 2.26 – 4.67 nM, while 3.2 7.29 nM. This approach will help medicinal chemists refine develop novel molecules targeting DDR2.

Language: Английский

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Expanding the potential of pyridine scaffold for targeted therapy of cancer: Biological activity, Molecular insights, and Structure-activity relationship

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1321, P. 139655 - 139655

Published: Aug. 22, 2024

Language: Английский

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Green one-pot synthesis of quinoxaline derivatives using sulfo-anthranilic acid functionalized alginate-MCFe₂O₄ nanostructures: a novel superparamagnetic catalyst with antiproliferative potential

RSC Advances, Journal Year: 2025, Volume and Issue: 15(3), P. 1698 - 1712

Published: Jan. 1, 2025

This study presents an eco-friendly, multi-component synthesis of 2-aminoimidazole–linked quinoxaline Schiff bases using a novel superparamagnetic acid catalyst.

Language: Английский

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Integrated Computational and Experimental Insights Into MEK1/2 Inhibitors: Structural Validation, Docking, ADMET, Molecular Dynamics, and Anticancer Evaluation

Chemistry & Biodiversity, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

This study explores the therapeutic potential of novel MEK1/2 inhibitors targeting MAPK pathway, emphasizing their critical role in cancer progression. An integrated computational approach, including molecular docking, pharmacophore modeling, dynamics simulations, and DFT analysis, was employed to evaluate binding affinity, stability, pharmacological properties FDA-approved experimental compounds. Structural validation MEK1 (PDB ID: 1S9J) MEK2 1S9I) revealed z-scores -6.89 -7.13, respectively, with 90.6% 86.7% residues most favored regions, confirming reliability protein models. Docking studies identified RO5126766 as a lead compound, exhibiting energies -10.1 kcal/mol -9.5 MEK2. Molecular simulations further demonstrated stability RO5126766-MEK1 RO5126766-MEK2 complexes, RMSD values ranging from 0.95 4.22 Å. The vitro anticancer assays highlighted exceptional potency RO5126766, IC50 12.87 ± 98.36 nM against MCF-7 (hormone receptor-positive breast cancer), 15.08 94.36 MDA-MB-231 (triple-negative 60.89 70.58 A549 (lung cancer). ADMET analysis confirmed high gastrointestinal absorption, favorable drug-likeness, lack blood-brain barrier permeability. In addition, indicated an optimal HOMO-LUMO energy gap (0.15816 eV), chemical hardness (0.16189 strong interactions corroborated by MEP analysis. Collectively, these findings establish potent selective inhibitor, demonstrating significant targeted agent for aggressive treatment-resistant cancers.

Language: Английский

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