Discovery of Novel Multiangiogenic Agents Targeting VEGFR2, EphB4, FGFR-1, and TIE-2: Receptor-Based Pharmacophore Modeling, Virtual Screening, and Molecular Modeling Studies

ACS Omega, Journal Year: 2025, Volume and Issue: 10(14), P. 13880 - 13897

Published: April 1, 2025

The angiogenesis phenomenon is crucial for the formation of new blood vessels in cancer cells. cancerous cells' progress hampers other healthy main objective this study to explore and decipher multimodal natural compounds against VEGFR2, EphB4, FGFR-1, TIE-2 drug targets arrest progression. receptor-based pharmacophore modeling was developed validated through enrichment parameters. Further, hypothesis allowed screening druglike product databases such as SuperNatural 3.0, COCONUT, LOTUS. common pharmacophoric featured were assessed binding affinities using absolute end-point methods. Finally, density functional theory has been studied understand chemical reactivity stability protein complexes. Among all screened compounds, 17 found align accurately models having higher fitness scores scores. Taking reference drugs sorafenib (VEGFR2), NVP-BHG712 (EphB4), pemiganitib (FGFR-1), DP1919 (TIE-2), three promising CNP0003920, CNP0243075, CNP0211397 concluded based on their energies, interactions, molecular dynamics, optimal pharmacokinetic toxicity profiles. (DFT) results suggested that identified bound with complexes are stable. Our findings can represent a starting point developing analogues proteins.

Language: Английский

Design, synthesis, biological evaluation and molecular docking study of novel quinolone derivatives as potent HDAC1 (Histone Deacetylase) inhibitors and anticancer agents

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: unknown, P. 141011 - 141011

Published: Dec. 1, 2024

Language: Английский

Anticancer Potential of Piperidine Containing Small Molecule Targeted Therapeutics

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(42)

Published: Nov. 1, 2024

Abstract In the past two decades, targeted anti‐cancer therapeutics have achieved remarkable success due to their exceptional advantages of selectivity towards cancer cells and safety. Targeted small molecule therapies persisted in many barriers; majorly poor response drug therapy. Piperidine, a heterocyclic moiety, exceeds twenty instances other pharmaceutical classes natural compounds form alkaloids effective treatment. The current review focuses on recent advancements, mainly from 2017–2023, piperidine‐containing development as agents. Total 10 piperidine containing drugs been approved by USFDA since 2017 till date around 15 inhibitors scaffold which are early discovery phase reviewed classified according biological target. It highlights structural contribution ring enhancement activity or pharmacokinetic properties diverse target‐specific angiogenesis, EGFR, VEGFR, ALK, AKT1, topoisomerase, CDK2 etc. role enhancing potency, bioavailability novel molecules has discussed. This will be helpful researchers, especially medicinal chemists, for designing potent specific targets cancer.

Language: Английский