Novel N -Arylmethyl-aniline/chalcone hybrids as potential VEGFR inhibitors: synthesis, biological evaluations, and molecular dynamic simulations DOI Creative Commons
Hesham Haffez, Nosaiba A. Elsayed, Marwa F. Ahmed

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: Nov. 20, 2023

Significant advancements have been made in the domain of targeted anticancer therapy for management malignancies recent times. VEGFR-2 is characterised by its pivotal involvement angiogenesis and subsequent mechanisms that promote tumour cells survival. Herein, novel N-arylmethyl-aniline/chalcone hybrids 5a–5n were designed synthesised as potential inhibitors. The activity was evaluated at NCI-USA, resulting identification 10 remarkably potent molecules 5a–5j further subjected to five-dose assays. Thereafter, they explored their inhibitory where 5e 5h emerged most induced apoptosis with cell cycle arrest SubG0-G1 phase within HCT-116 cells. Moreover, impact on some key apoptotic genes assessed, suggesting caspase-dependent apoptosis. Furthermore, molecular docking dynamics simulations conducted explore binding modes stability protein–ligand complexes.

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

6
New thiazolidine-2,4-diones as potential anticancer agents and apoptotic inducers targeting VEGFR-2 kinase: Design, synthesis, in silico and in vitro studies DOI
Hazem Elkady,

Hazem A. Mahdy,

Mohammed S. Taghour

et al.

Biochimica et Biophysica Acta (BBA) - General Subjects, Journal Year: 2024, Volume and Issue: 1868(6), P. 130599 - 130599

Published: March 22, 2024

Language: Английский

Citations

4
Research on university laboratory management and maintenance framework based on computer aided technology DOI Open Access
Jiaqing Yao,

Zheng Yuan

Applied Mathematics and Nonlinear Sciences, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 1, 2025

Abstract This With the development of information technology, university laboratories play an increasingly important role in teaching and research. However, traditional laboratory management methods have many shortcomings terms resource scheduling, system flexibility, automation, making it difficult to adapt constantly changing demands complex experimental environments. Traditional often rely on manual management, resulting low utilization efficiency potential waste or scheduling imbalance under high concurrency conditions. Moreover, models lack real-time monitoring flexible capabilities, failing meet requirements efficient modern management. To address these issues, this paper proposes a computer method based virtualization technology. By designing multi-layer platform architecture, including layer, desktop service foundation complete is formed, enhancing automation levels. also introduces Column Generation-based Shared Resource Constrained Project Scheduling Algorithm (CGS) achieve allocation optimized scheduling. Experimental results show that proposed outperforms utilization, task completion time, providing effective solution for

Language: Английский

Citations

0
Design and synthesis of thiadiazoles as anticancer, apoptotic, and VEGFR-2 inhibitors DOI
Walid E. Elgammal, Hazem Elkady, Mohammed A. Dahab

et al.

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: April 8, 2025

Vascular endothelial growth factor receptor (VEGFR-2) inhibitors are critical in cancer therapy due to their role suppressing tumor angiogenesis. Herein, we report a new series of thiadiazole-based derivatives as potential VEGFR-2 with promising anticancer activity. The synthesized compounds were evaluated for anti-proliferative activity against human cell lines (HCT-116, MCF-7, and HepG-2), WI-38 normal cells. Sorafenib was used reference drug. inhibitory determined, followed by cycle analysis, apoptosis assays, Q-RT-PCR wound-healing assays. In silico molecular docking conducted explore binding interactions. Among the tested compounds, 13b exhibited potent (IC50: 3.98-11.81 µM) strong inhibition 41.51 nM), surpassing sorafenib 53.32 nM). Cell analysis revealed that induced G2/M phase arrest MCF-7 Apoptosis levels increased from 2% 52%, accompanied > 12-fold rise Bax/Bcl-2 ratio activation caspase-8/9. Additionally, significantly suppressed migration, only 5.28% wound closure. studies confirmed its Thiadiazole-based derivatives, particularly compound 13b, exhibit inhibition, effects, induction, anti-migratory activity, supporting agents.

Language: Английский

Citations

0
In Vitro and In Silico Evaluation of the Anticancer and Antiparasitic Activities of New 2‐Methoxy Azachalconium Bromides DOI
Mai F. AlSakhen, Sana I. Kanaan, Khaled Saleh

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(16)

Published: April 1, 2025

Abstract Three new N ‐alkylpyridinium‐based 2‐methoxy chalcones with long, fatty alkyl chains were prepared and tested for their anticancer antiparasitic activities. The ‐octadecyl derivative ( 2c ) displayed considerable activity against selectivity BRAF‐mutant HT‐29 colorectal carcinoma cells. Increased mRNA expression of caspases apoptosis induction was found. In addition, MEKs ERKs upregulated. EGFR inhibition identified as mechanism action this compound further supported by in silico molecular docking studies, which revealed a binding energy −9.19 kcal/mol EGFR. Additionally, strong affinity VEGFR‐2 observed −11.01 kcal/mol. development the described chalcone drug appears to be promising. all three derivatives exhibited significant activities Toxoplasma gondii Leishmania major parasites, albeit without selectivity. Thus, present study describes first time kinase‐inhibitory, anti‐leishmanial, anti‐toxoplasmal ‐alkyl azachalconium compounds.

Language: Английский

Citations

0
Computer-assisted drug discovery (CADD) of an anti-cancer derivative of the theobromine alkaloid inhibiting VEGFR-2 DOI Creative Commons
Ibrahim H. Eissa, Reda G. Yousef, Mostafa A. Asmaey

et al.

Saudi Pharmaceutical Journal, Journal Year: 2023, Volume and Issue: 31(12), P. 101852 - 101852

Published: Nov. 3, 2023

VEGFR-2 is a significant target in cancer treatment, inhibiting angiogenesis and impeding tumor growth. Utilizing the essential pharmacophoric structural properties, new semi-synthetic theobromine analogue (T-1-MBHEPA) was designed as inhibitor. Firstly, T-1-MBHEPA's stability reactivity were indicated through several DFT computations. Additionally, molecular docking, MD simulations, MM-GPSA, PLIP, dynamics (ED) experiments suggested strong binding capabilities to VEGFR-2. Its computational ADMET profiles also studied before semi-synthesis good degree of drug-likeness. T-1-MBHEPA then semi-synthesized evaluate design silico findings. It found that, inhibited with an IC50 value 0.121 ± 0.051 µM, compared sorafenib which had 0.056 µM. Similarly, proliferation HepG2 MCF7 cell lines values 4.61 4.85 µg/mL respectively - comparing sorafenib's 2.24 3.17 respectively. Interestingly, revealed noteworthy 80.0 µM against normal exhibiting exceptionally high selectivity indexes (SI) 17.4 16. 5 examined lines, increased percentage apoptotic cells early late stages, respectively, from 0.71 % 7.22 0.13 2.72 %, while necrosis 11.41 comparison 2.22 control cells. Furthermore, reduced production pro-inflammatory cytokines TNF-α IL-2 treated by 33 58 indicating additional anti-angiogenic mechanism. Also, decreased significantly potentialities heal migrate 65.9 7.4 %. Finally, oral treatment didn't show toxicity on liver function (ALT AST) kidney (creatinine urea) levels mice.

Language: Английский

Citations

10
New benzimidazole‐oxadiazole derivatives as potent VEGFR‐2 inhibitors: Synthesis, anticancer evaluation, and docking study DOI Creative Commons
Ulviye Acar Çevik, İsmail Çeli̇k, Şennur Görgülü

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(4)

Published: June 1, 2024

Abstract We report herein, the design and synthesis of benzimidazole‐oxadiazole derivatives as new inhibitors for vascular endothelial growth factor receptor‐2 (VEGFR‐2). The designed members were assessed their in vitro anticancer activity against three cancer cell lines two normal lines; A549, MCF‐7, PANC‐1, hTERT‐HPNE CCD‐19Lu. Compounds 4c 4d found to be most effective compounds lines. then tested VEGFR‐2 inhibitory activity, safety profiles, selectivity indices using CCD‐19Lu It was determined that compound safe member produced chemical family. Vascular A (VEGFA) immunolocalizations evaluated relative control by VEGFA immunofluorescence staining. inhibited enzyme with half‐maximal concentration values 0.475 ± 0.021 0.618 0.028 µM, respectively. Molecular docking target carried out active site (Protein Data Bank: 4ASD).

Language: Английский

Citations

3
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

3
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

8
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

1