Design, synthesis, and antiproliferative activity of new 1,2,3-triazole/quinazoline-4-one hybrids as dual EGFR/BRAFV600E inhibitors DOI Creative Commons

Amira M. Mohamed,

Ola M. F. Abou‐Ghadir,

Yaser A. Mostafa

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(52), P. 38403 - 38415

Published: Jan. 1, 2024

A series of new quinazoline/1,2,3-triazole hybrids were designed and synthesized. The compounds evaluated as antiproliferative agents targeting EGFR, BRAF V600E .

Language: Английский

Benzimidazole‐oxindole hybrids: A novel class of selective dual CDK2 and GSK‐3β inhibitors of potent anticancer activity DOI
Heba T. Abdel‐Mohsen, Yasmin M. Syam,

Mahmoud S. Abd El‐Ghany

et al.

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 357(10)

Published: July 23, 2024

Abstract A new series of benzimidazole‐oxindole hybrids 8a–x was discovered as dual cyclin‐dependent kinase (CDK2) and glycogen synthase kinase‐3‐beta (GSK‐3β) inhibitors with potent anticancer activity. The synthesized hits displayed activity against national cancer institute cell lines in single‐dose five‐dose assays. Moreover, the derivatives 8k , 8l 8n, 8o 8p demonstrated cytotoxic PANC‐1 cells IC 50 = 1.88–2.79 µM. In addition, 8n antiproliferative on MG‐63 line (IC 0.99–1.90 µM). Concurrently, hybrid 8v exhibited CDK2/GSK‐3β inhibitory values 0.04 0.021 µM, respectively. more than 10‐fold higher selectivity toward CDK2 GSK‐3 β over CDK1, CDK5, GSK‐3α, vascular endothelial growth factor receptor‐2, B‐rapidly accelerated fibrosarcoma. Screening effect cycle apoptosis their ability to arrest at G2‐M phase potentiate both lines. silico docking into catalytic pocket GSK‐3β revealed its perfect fitting through formation hydrogen bonding hydrophobic interactions key amino acids binding sites. absorption, distribution, metabolism, excretion studies proved that exhibit satisfactory drug‐likeness properties for drug development.

Language: Английский

Citations

8
Quinazoline‐oxindole hybrids as angiokinase inhibitors and anticancer agents: Design, synthesis, biological evaluation, and molecular docking studies DOI
Yasmin M. Syam, Somaia S. Abd El‐Karim, Heba T. Abdel‐Mohsen

et al.

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 357(10)

Published: July 12, 2024

Two new sets of quinazoline-oxindole 8a-l and quinazoline-dioxoisoindoline 10a-d hybrids were designed as type II angiokinase inhibitors anticancer agents. The design strategy was adjusted to account for the quinazoline scaffold's placement in target kinases' hinge region, where it would form hydrogen bonding hydrophobic interactions with important amino acids stabilize it, amide group's occupation gate which direct oxindole scaffold toward back pocket. two quinazolines displayed pronounced inhibitory activity on VEGFR-2 (IC

Language: Английский

Citations

7
Discovery of novel diaryl urea-oxindole hybrids as BRAF kinase inhibitors targeting BRAF and KRAS mutant cancers DOI
Iman A. Y. Ghannam, Ahmed M. El Kerdawy, Marwa M. Mounier

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 153, P. 107848 - 107848

Published: Sept. 27, 2024

Language: Английский

Citations

6
Spiroindoline quinazolinedione derivatives as inhibitors of P-glycoprotein: potential agents for overcoming multidrug resistance in cancer therapy DOI
Fatemeh Moosavi,

Masoumeh Divar,

Soghra Khabnadideh

et al.

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Language: Английский

Citations

0
Green synthesis, in silico modeling, and biological evaluation of N-substituted (Z)-5-arylidene imidazolidine/thiazolidine-2,4-dione/4-thione derivatives catalyzed by Bu SO3H core–shell nanostructures DOI Creative Commons
Malihe Akhavan, Zohreh Esam,

Atefeh Mirshafa

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(32), P. 22916 - 22938

Published: Jan. 1, 2024

The newly designed magnetic nanocatalyst Fe 3 O 4 @CPTMS@guanidine–BuSO H in a one-pot multicomponent reaction is reported to obtain N -substituted ( Z )-5-arylidene imidazolidine/thiazolidine-2,4-dione/4-thione as highly selective antiproliferation agent.

Language: Английский

Citations

4
Diphenyl urea‐benzylidene acetohydrazide hybrids as fibroblast growth factor receptor 1 inhibitors and anticancer agents DOI
Heba T. Abdel‐Mohsen, Amira M. Nageeb, Iman A. Y. Ghannam

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(6)

Published: Aug. 24, 2024

Abstract Molecular hybridization between diphenyl urea and benzylidene acetohydrazide was adopted for the design of a new series FGFR‐1 targeting cancer. The designed synthesized submitted to NCI‐USA be screened their growth inhibitory activity on NCI cancer cell lines. Some hybrids displayed promising lines with mean GI% 70.39% lethal effect. Compounds 9a , 9i 9j 9n‐p were further selected five‐dose assay all tested candidates showed antiproliferative GI 50 reaching submicromolar range. Encouraged by potent colon one hand well‐known overexpression in it other hand, as representative example evaluated its mechanism cycle apoptosis HCT116 line. Interestingly, found pause line at G1 phase induced late apoptosis. In parallel, 9a‐p examined potential inhibit 10 µM. 9g 9h 9p have % inhibition = 63.04%, 58.31%, 60.87% 79.84%, respectively. docking simulation binding pocket confirms capability achieve characteristic interactions type II inhibitors. Exploration ADME properties SwissADME web tool proved satisfactory physicochemical discovery anticancer hits.

Language: Английский

Citations

4
Benzimidazole–dioxoisoindoline conjugates as dual VEGFR-2 and FGFR-1 inhibitors: design, synthesis, biological investigation, molecular docking studies and ADME predictions DOI Creative Commons
Heba T. Abdel‐Mohsen, Amira M. Nageeb

RSC Advances, Journal Year: 2024, Volume and Issue: 14(39), P. 28889 - 28903

Published: Jan. 1, 2024

A series of new benzimidazole–dioxo(benzo)isoindoline conjugates were designed and synthesized as dual VEGFR-2 FGFR-1 inhibitors. Compound 8m demonstrated potent % inhibition 80.69% 76.83% on at 10 μM, respectively.

Language: Английский

Citations

3
Oxindole–benzothiazole hybrids as CDK2 inhibitors and anticancer agents: design, synthesis and biological evaluation DOI Creative Commons
Heba T. Abdel‐Mohsen

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

Published: Sept. 13, 2024

Abstract In the current study, molecular hybridization between oxindole core and benzothiazole system through an acetohydrazide moiety was accomplished for design of a new series oxindole–benzothiazole hybrids 9a – r targeting CDK2 cancer therapy. The afforded displayed promising growth inhibitory activity on NCI cell lines at 10 µM. Compound 9o mean GI% = 55.91%. Based potent , it further assessed its cytotoxic five dose level demonstrated GI 50 reaching 2.02 Analysis cycle prostate line DU145 after treatment with confirmed ability to arrest G1 phase. Moreover, proved potentiate apoptosis necrosis same line. Furthermore, 9b 9f showed IC 0.70, 0.20 0.21 µM, respectively CDK2. Besides, docking simulation synthesized hybrid expected binding mode which involves accommodation in ATP pocket where is involved hydrogen bonding hydrophobic interactions essential amino acids hinge region while oriented toward solvent region. Investigation physicochemical properties highlights their acceptable ADME that can be somewhat developed discovery anticancer agents.

Language: Английский

Citations

2
Pd-catalysed regioselective cross dehydrogenative coupling of quinazolinones with aromatic carboxylic acids DOI

Deepali S. Waghmare,

Priyanka M. Lagad,

Umesh A. Kshirsagar

et al.

Tetrahedron Letters, Journal Year: 2024, Volume and Issue: 147, P. 155214 - 155214

Published: July 23, 2024

Language: Английский

Citations

0
Design, synthesis, and antiproliferative activity of new 1,2,3-triazole/quinazoline-4-one hybrids as dual EGFR/BRAFV600E inhibitors DOI Creative Commons

Amira M. Mohamed,

Ola M. F. Abou‐Ghadir,

Yaser A. Mostafa

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(52), P. 38403 - 38415

Published: Jan. 1, 2024

A series of new quinazoline/1,2,3-triazole hybrids were designed and synthesized. The compounds evaluated as antiproliferative agents targeting EGFR, BRAF V600E .

Language: Английский

Citations

0