New Benzofuran–Pyrazole-Based Compounds as Promising Antimicrobial Agents: Design, Synthesis, DNA Gyrase B Inhibition, and In Silico Studies DOI Creative Commons
Somaia S. Abd El‐Karim, Manal M. Anwar, Yasmin M. Syam

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1664 - 1664

Published: Dec. 10, 2024

Background/Objectives: The alarming rise in antibiotic resistance necessitates the discovery of novel antimicrobial agents. This study aims to design, synthesize, and evaluate new benzofuran–pyrazole-based compounds for their antimicrobial, antioxidant, anti-inflammatory properties. Methods: New benzofuran–pyrazole hybrid molecules were synthesized using Vilsmeier–Haach reaction other chemical processes. structures confirmed through micro-analytical spectral analyses. Their activities assessed against various bacterial fungal strains, while antioxidant properties evaluated DPPH-free radical scavenging HRBC membrane stabilization assays, respectively. most promising further tested DNA gyrase B inhibition. Results: Compounds 9, 10, 11b–d exhibited significant broad-spectrum activity with MIC values ranging from 2.50 20 µg/mL. 4, 6, 11b, 11d demonstrated high activity, DPPH percentages between 84.16% 90.52%. Most showed substantial effects, 86.70% 99.25%. Compound 9 notably inhibited E. coli an IC50 9.80 µM, comparable ciprofloxacin. Conclusions: compounds, particularly compound show great potential as agents due potent These findings support development optimization these clinical applications.

Language: Английский

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
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
2‐Indolinone: An Anticancer Scaffold, Overview of the Studies and Approaches (2017–2024) DOI Open Access
Taha Koulani, Asu Büşra Temizer, Nilgün Karalı

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(5)

Published: Feb. 1, 2025

Abstract 2‐Indolinone is a versatile scaffold that has been the central moiety in structure of various drugs. Since introduction sunitinib malate, 2‐indolinones have principal pharmacophoric building block many drug discovery studies, especially last few years. Compounds bearing 2‐indolinone ring system shown therapeutic effects, including but not limited to, antidiabetic, antioxidant, anti‐inflammatory, anti‐HIV, antimicrobial, antipsychotic, antiparkinson, and anticancer activities. Considering cancer among major global causes death, antiproliferative activities these compounds goal numerous studies. The present review presents an overview approaches advances made during eight years (2017–2024) regarding development derivatives within field discovery. derivates gathered herein are classified according to target developed compounds, notable structure‐activity relationships as well significant molecular docking interactions with enzymes highlighted each instance. Accordingly, special attention paid reporting superior enzymatic inhibitory effects emerged lead respective study.

Language: Английский

Citations

0
Novel 5,6-dichlorobenzimidazole derivatives as dual BRAFWT and BRAFV600E inhibitors: design, synthesis, anti-cancer activity and molecular dynamics simulations DOI Creative Commons
Ahmed Temirak, Ahmed M. El Kerdawy, Amira M. Nageeb

et al.

BMC Chemistry, Journal Year: 2025, Volume and Issue: 19(1)

Published: Feb. 21, 2025

Language: Английский

Citations

0
Design and synthesis of novel pyrimidine-pyrazole hybrids with dual anticancer and anti-inflammatory effects targeting BRAFV600E and JNK DOI Creative Commons
Mohammed S. Abdel‐Maksoud, Hebatollah E. Eitah, Rasha M. Hassan

et al.

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

Published: Feb. 22, 2025

Abstract Two new series of pyrimidinyl ethyl pyrazoles derivatives 13a–f and 14a–f were designed synthesized to possess both anticancer effect by inhibiting BRAFV600E anti-inflammatory JNK isoforms. The structure the compounds was generated from hybridization two main moieties. moiety reported inhibitors, pyrazole isoforms inhibitors. final tested on BRAFV600E, JNK1, JNK2, JNK3 measure their kinases inhibitory effect. Compound 14c showed highest activity with IC 50 = 0.51 μM, 0.53 1.02 0.009 μM JNK3,and respectively. All over four cancer cell lines related target enzymes. 14d most potent all 0.87 0.91, 0.42 0.63 MOLT-4, K-562, SK-MEL-28, A375 lines, ability inhibit MEK1/2 ERK1/2 phosphorylation performed using western blot. cycle analysis compound line revealed that arrested growth at G0-G1 phase. remarkably decreased migration compared control group in traditional test. Compounds significant nitric oxide release PGE2 production raw 264.7 macrophages. 13d 1 4d exhibited high iNOS COX-2 COX-1. Finally, TNF-alpha IL-6 determined. Graphical abstract synthesized. able BRAFV600E. play a key role inflammatory disorders. Final for activities.

Language: Английский

Citations

0
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
New Benzofuran–Pyrazole-Based Compounds as Promising Antimicrobial Agents: Design, Synthesis, DNA Gyrase B Inhibition, and In Silico Studies DOI Creative Commons
Somaia S. Abd El‐Karim, Manal M. Anwar, Yasmin M. Syam

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1664 - 1664

Published: Dec. 10, 2024

Background/Objectives: The alarming rise in antibiotic resistance necessitates the discovery of novel antimicrobial agents. This study aims to design, synthesize, and evaluate new benzofuran–pyrazole-based compounds for their antimicrobial, antioxidant, anti-inflammatory properties. Methods: New benzofuran–pyrazole hybrid molecules were synthesized using Vilsmeier–Haach reaction other chemical processes. structures confirmed through micro-analytical spectral analyses. Their activities assessed against various bacterial fungal strains, while antioxidant properties evaluated DPPH-free radical scavenging HRBC membrane stabilization assays, respectively. most promising further tested DNA gyrase B inhibition. Results: Compounds 9, 10, 11b–d exhibited significant broad-spectrum activity with MIC values ranging from 2.50 20 µg/mL. 4, 6, 11b, 11d demonstrated high activity, DPPH percentages between 84.16% 90.52%. Most showed substantial effects, 86.70% 99.25%. Compound 9 notably inhibited E. coli an IC50 9.80 µM, comparable ciprofloxacin. Conclusions: compounds, particularly compound show great potential as agents due potent These findings support development optimization these clinical applications.

Language: Английский

Citations

0