Design, synthesis, and biological investigations of new pyrazole derivatives as VEGFR2/CDK-2 inhibitors targeting liver cancer DOI Creative Commons
Manar G. Salem, Mohamed S. Nafie,

Aya A. Elzamek

et al.

BMC Chemistry, Journal Year: 2024, Volume and Issue: 18(1)

Published: Oct. 24, 2024

Abstract New Series of N -Manniche bases 3,4 (a-c) and 5,6 (a-b) were synthesized through the reaction benzaldehyde amine with 3-methyl-4-(aryldiazenyl)-1H-pyrazol-5-ol derivatives 2(a-c), they fully characterized by FT-IR, ( 1 H, 13 C) NMR data in addition to their mass spectra. The Structural Activity Relationship target compounds examined for cytotoxicity. Some newly showed promising antiproliferation properties when tested against HepG2 cancer cells. Compounds 4a, 5a, 6b potent cytotoxicity IC 50 values 4.4, 3.46 2.52 µM compared Sorafenib (IC = 2.051 µM) Roscovitine 4.18 µM). Furthermore, safe THLE2 cells higher values. Compound exhibited dual VEGFR2/CDK-2 inhibition activities; it had an value 0.2 μM VEGFR2 93.2%, 0.458 CDK-2 88.7%. In comparison untreated control group (0.95%), 5a (38.32%) (42.9%) considerably increased cell population total apoptosis. addition, arrested at G0-G1 S phases, respectively. Molecular docking experiments confirmed virtual binding mechanism most active drugs, which found have good affinities both receptor sites.

Language: Английский

Discovery of new thiazolidine-2,4-dione derivatives as potential VEGFR-2 inhibitors: In vitro and in silico studies DOI Creative Commons
Ibrahim H. Eissa, Hazem Elkady, Mahmoud Rashed

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(2), P. e24005 - e24005

Published: Jan. 1, 2024

In this study, a series of seven novel 2,4-dioxothiazolidine derivatives with potential anticancer and VEGFR-2 inhibiting abilities were designed synthesized as inhibitors. The compounds tested in vitro for their to inhibit the growth HepG2 MCF-7 cancer cell lines. Among tested, compound 22 (IC50 = 0.079 μM) demonstrated highest anti-VEGFR-2 efficacy. Furthermore, it significant anti-proliferative activities against 2.04 ± 0.06 1.21 0.04 M). Additionally, also increased total apoptotic rate lines cycle arrest at S phase. As well, computational methods applied study VEGFR-2-22 complex molecular level. Molecular docking dynamics (MD) simulations used investigate complex's structural kinetic characteristics. DFT calculations further revealed electronic properties 22. Finally, ADMET toxicity tests performed indicating likeness proposed be drugs. results suggest that displays promise an effective treatment can serve model future modifications biological investigations field.

Language: Английский

Citations

7
Design, synthesis, in vitro, and in silico studies of new thiadiazol derivatives as promising VEGFR-2 inhibitors and apoptosis inducers DOI

Hazem A. Mahdy,

Hazem Elkady, Walid E. Elgammal

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1316, P. 139019 - 139019

Published: June 19, 2024

Language: Английский

Citations

6
Integrated in silico and in vitro discovery of a new anticancer thiadiazole analog targeting VEGFR-2 DOI
Ibrahim H. Eissa, Hazem Elkady, Walid E. Elgammal

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1312, P. 138641 - 138641

Published: May 15, 2024

Language: Английский

Citations

5
Anti-breast cancer potential of a new xanthine derivative: In silico, antiproliferative, selectivity, VEGFR-2 inhibition, apoptosis induction and migration inhibition studies DOI
Ibrahim H. Eissa, Reda G. Yousef, Hazem Elkady

et al.

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 251, P. 154894 - 154894

Published: Oct. 14, 2023

Language: Английский

Citations

11
Rationale design and synthesis of new apoptotic thiadiazole derivatives targeting VEGFR-2: computational and in vitro studies DOI Creative Commons
Walid E. Elgammal, Hazem Elkady,

Hazem A. Mahdy

et al.

RSC Advances, Journal Year: 2023, Volume and Issue: 13(51), P. 35853 - 35876

Published: Jan. 1, 2023

This work presents the synthesis and in vitro, silico analyses of new thiadiazole derivatives that are designed to mimic pharmacophoric characteristics vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. A comprehensive evaluation inhibitory properties synthesized against cancer cell lines MCF-7 HepG2 identified several auspicious candidates. Among them, compound 14 showed remarkably low IC50 values 0.04 μM 0.18 HepG2, respectively. VEGFR-2 revealed a promising value nanomolar range (103 nM). Further examination cycle has ability stop progression cells via G0-G1 phase arrest. Interestingly, also demonstrated noteworthy pro-apoptotic effect cells, with notable increases early apoptosis (16.53%) late (29.57%), along slight increase population necrotic (5.95%). Furthermore, significant drop cells' migrate heal wounds. Additionally, promoted by boosting BAX (6-fold) while lowering Bcl-2 (6.2-fold). The binding affinities candidates their target were confirmed computational investigations, including molecular docking, principal component analysis trajectories (PCAT), dynamics (MD) simulations. 14's stability reactivity investigated using density functional theory (DFT). These thorough results highlight potential as lead contender for additional research creation anticancer drugs VEGFR-2. establishes foundation future therapeutic developments anticancer- angiogenesis-related scientific fields.

Language: Английский

Citations

10
Nicotinamide Loaded Chitosan Nanocomplex Shows Improved Anticancer Potential: Molecular Docking, Synthesis, Characterization and In vitro Evaluations DOI
Ahmed M. Metwaly, M.A. Abu-Saied,

Ibraheem M. M. Gobaara

et al.

Current Organic Chemistry, Journal Year: 2024, Volume and Issue: 28(1), P. 46 - 55

Published: Jan. 1, 2024

Abstract: This study aimed to prepare and characterize chitosan nanoparticles encapsulating a nicotinamide derivative (Ni-CS-NP). Additionally, the therapeutic effectiveness, cytotoxicity, selectivity, immunomodulatory properties of Ni-CS-NP were evaluated in human breast colon cancer cell lines. Chitosan have shown potential as drug delivery carriers due their biocompatibility controlled release properties. Encapsulating further enhances these nanoparticles. Computational studies employed validate binding interactions, providing crucial insights into formulation's stability effectiveness. The primary objective was assess cytotoxicity safety profiles Moreover, this investigate specific mechanisms underlying its cytotoxic effects, including impact on cycle progression, apoptosis induction, immunomodulation. synthesized using ionic gelation method characterized Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission (TEM), thermo gravimetric analysis. lines through MTT assay. Selectivity indices calculated determine profiles. inhibition VEGFR-2, induction apoptosis, disruption, effects assessed molecular assays. analysis demonstrated favorable interactions complex. characterization confirmed successful synthesis with well-defined structural thermal exhibited remarkable superior profile against MCF7 HCT 116 showing IC50 values 2.32 2.70 μM, respectively, surpassing sorafenib's efficacy (IC50 = 4.12 7.55 respectively). effectively inhibited induced both early late disrupted progression cells. Notably, significant by reducing TNF-α IL-2 levels compared dexamethasone. encapsulation within (Ni-CS-NP) proved successful. displayed potent profiles, promising These findings highlight novel agent for treatment, warranting investigation clinical applications.

Language: Английский

Citations

4
Anti-proliferative 2,3-dihydro-1,3,4-thiadiazoles targeting VEGFR-2: Design, synthesis, in vitro, and in silico studies DOI
Hazem Elkady, Walid E. Elgammal,

Hazem A. Mahdy

et al.

Computational Biology and Chemistry, Journal Year: 2024, Volume and Issue: 113, P. 108221 - 108221

Published: Sept. 23, 2024

Language: Английский

Citations

4
Targeting Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2): Latest Insights on Synthetic Strategies DOI Creative Commons
Carolina S. Marques, Pedro Brandão, Anthony J. Burke

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5341 - 5341

Published: Nov. 13, 2024

Vascular endothelial growth factor receptor 2 (VEGFR-2) is a crucial mediator of angiogenesis, playing pivotal role in both normal physiological processes and cancer progression. Tumors harness VEGFR-2 signaling to promote abnormal blood vessel growth, which key step the metastasis process, making it valuable target for anticancer drug development. While there are inhibitors approved therapeutic use, they face challenges like resistance, off-target effects, adverse side limiting their effectiveness. The quest new candidates with inhibitory activity often starts selection structural motifs present molecules currently used clinical practice, expanding chemical space by generating novel derivatives bearing one or more these moieties. This review provides an overview recent advances development inhibitors, focusing on synthesis promising antiproliferative inhibition activities, organizing them relevant features.

Language: Английский

Citations

4
Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer DOI Creative Commons
Eslam B. Elkaeed, Hazem Elkady, Ahmed M. Khattab

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0316146 - e0316146

Published: Jan. 27, 2025

This study presents T-1-NBAB , a new compound derived from the natural xanthine alkaloid theobromine, aimed at inhibiting VEGFR-2, crucial protein in angiogenesis. ’s potential to interacts with and inhibit VEGFR-2 was indicated using silico techniques like molecular docking, MD simulations, MM-GBSA, PLIP, essential dynamics, bi-dimensional projection experiments. DFT experiments utilized also structural electrostatic properties of . Computational analysis performed predict ADME-Tox profiles After semisynthesis, vitro results showed that effectively inhibits an IC 50 0.115 μM, compared sorafenib’s 0.0591 μM. In tests demonstrated significant activity against breast cancer cell lines MCF7 T47D, values 16.88 μM 61.17 respectively, high selectivity. Importantly, induced early late apoptosis cells, indicating its as strong anticancer agent. Additionally, reduced migration healing abilities suggesting it could be promising anti-angiogenic Overall, these findings suggest is lead for further research treatment cancer.

Language: Английский

Citations

0
Anti-breast cancer potential of thieno-pyrimidine derivatives as VEGFR-2 inhibitors DOI
Aisha A. Alsfouk, Maged Mohammed Saleh Al Ward,

Mustafa A. Al-Qadhi

et al.

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: March 17, 2025

Background Thieno-pyrimidine derivatives have emerged as promising candidates for VEGFR-2 inhibition. This study aimed to design, synthesize, and evaluate novel thieno-pyrimidine their anti-cancer potential.

Language: Английский

Citations

0