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January 23, 2026Molecular DiversityOpen Access

Novel pyrazole–oxadiazole–chalcone/oxime hybrids as dual EGFR/VEGFR-2 inhibitors with promising anticancer potential: a comprehensive cytotoxicity evaluation, mechanistic insights and SAR analysis

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Population

NCI-60 human cancer cell line panel and MCF-7 cells

Comparison

Novel pyrazole-1,3,4-oxadiazole hybrids incorporating chalcone/oxime scaffolds

Design

In vitro preclinical study

Key result

Compound 11b, a dual EGFR/VEGFR-2 inhibitor, showed the highest potency with IC₅₀ values of 26.38 nM and 114.17 nM, respectively, and induced apoptotic pathways in MCF-7 cells.

Authors

OAOmar AlshazlyMAMohamed Abdel-azizGAGamal El-Din A. Abuo-Rahma

Discussion

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Overview

Hypothesis-generating for dual EGFR/VEGFR-2 inhibition; leaves open clinical translation pending in vivo validation.

Key Points

  • The study aims to evaluate novel pyrazole-oxadiazole hybrids for their dual inhibitory effects on EGFR and VEGFR-2 and their anticancer potential.
  • Synthesis of pyrazole-1,3,4-oxadiazole hybrids with chalcone/oxime scaffolds
  • Assessment of cytotoxicity using the NCI-60 human cancer cell line panel
  • Mechanistic studies on apoptosis and G2/M phase arrest in MCF-7 cells
  • Molecular docking and structure-activity relationship analysis to evaluate binding interactions.
  • Several compounds, especially 10b, 11a, and 11b, showed broad-spectrum growth inhibition with mean GI₅₀ values of 4.36–16.4 µM.
  • Compound 11b exhibited the highest potency as a dual inhibitor with IC₅₀ values of 26.38 nM for EGFR and 114.17 nM for VEGFR-2.
  • Mechanistic assessments revealed 11b induced G2/M phase arrest and apoptosis in MCF-7 cells.
  • Oxime derivatives enhanced nitric oxide release, contributing to their anticancer activity.

Structured PICO

P
Population
NCI-60 human cancer cell line panel (derived from leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast cancer) and MCF-7 cells
I
Intervention
Novel pyrazole–1,3,4-oxadiazole hybrids incorporating chalcone/oxime scaffolds (compounds 10a-10c, 11a-11c, 12a-12i, 13a-13i, and 14a-14i), specifically compound 11b
C
Comparator
Untreated reference cells and reference drug gefitinib
O
Outcome
In vitro cytotoxicity (GI50, TGI, LC50) and EGFR/VEGFR-2 inhibitory activity (IC50)surrogate

Compound 11b emerged as a promising dual EGFR/VEGFR-2 inhibitor with potent broad-spectrum anticancer activity and NO-releasing properties in vitro.

Cite This Study

Alshazly et al. (2026) studied this question. Compound 11b, a dual EGFR/VEGFR-2 inhibitor, showed the highest potency with IC₅₀ values of 26.38 nM and 114.17 nM, respectively, and induced apoptotic pathways in MCF-7 cells.

synapsesocial.com/papers/69730f59c8125b09b0d1f1bfhttps://doi.org/10.1007/s11030-025-11411-3
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