Rational Design of Triazole Hydrazide Derivatives With Imidazo[2,1‐
                    b
                    ]thiazole Scaffolds as Targeted EGFR Inhibitors in NSCLC

Mohamed K. Elgohary; Mahmoud S. Elkotamy; Zainab M. Elsayed; Abrar Mortada Abdelraheem; Ibrahim Taha Radwan; Eman Darweish; Abdulrahman A. Almehizia; Ahmed M. Naglah; Fahad A. Almehizia; Mohamed Fares; Wagdy M. Eldehna; Hatem A. Abdel‐Aziz

doi:10.1002/ddr.70211

journal article Dec 17, 2025

Rational Design of Triazole Hydrazide Derivatives With Imidazo[2,1‐ b ]thiazole Scaffolds as Targeted EGFR Inhibitors in NSCLC

Mohamed K. Elgohary

Mahmoud S. Elkotamy Zainab M. Elsayed Abrar Mortada Abdelraheem Ibrahim Taha Radwan Eman Darweish

Abdulrahman A. Almehizia Ahmed M. Naglah

Fahad A. Almehizia Mohamed Fares Wagdy M. Eldehna

Hatem A. Abdel‐Aziz

Drug Development Research Vol. 87 No. 1 · Wiley

View at Publisher Save 10.1002/ddr.70211

Abstract

ABSTRACT

A novel series of triazole hydrazide derivatives
8a‐o
was rationally designed, synthesized, and systematically evaluated for their anticancer potential. Cytotoxicity screening against A549 lung adenocarcinoma cells identified compounds
8a‐d
as the most potent, exhibiting IC
50
values of 3.15–4.93 µM, which are comparable to doxorubicin (IC
50
= 2.77 µM). Mechanistic studies revealed that lead compound
8a
induced apoptosis through upregulation of Bax and caspase‐3 and downregulation of Bcl‐2. Additionally,
8a
significantly inhibited A549 cell migration (34.46% wound closure vs. 61.61% in controls) and reduced clonogenic survival (surviving fraction = 0.5725). Importantly,
8a
displayed low cytotoxicity toward normal lung fibroblasts (WI‐38, IC
50
= 47.21 µM). Enzyme inhibition assays demonstrated potent EGFR kinase inhibition by
8a
and
8 d
(IC
50
= 74.85 and 75.87 nM, respectively), comparable to erlotinib (IC
50
= 34.89 nM). Moreover,
in silico
ADMET profiling predicted favorable drug‐likeness and oral bioavailability, while molecular docking supported the stable binding of
8a
within the EGFR active site. These findings identify compound
8a
as a promising therapeutic lead for the development of targeted EGFR inhibitors in non‐small cell lung cancer (NSCLC) therapy.

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Details

Published: Dec 17, 2025
Vol/Issue: 87(1)
License: View

Authors

M

Mohamed K. Elgohary

Pharmaceutical Chemistry Department, Faculty of Pharmacy Egyptian Russian University Badr City Egypt

M

Mahmoud S. Elkotamy

Department of Pharmaceutical Chemistry, Faculty of Pharmacy Alsalam University Kafr El Zayat Egypt

Z

Zainab M. Elsayed

Scientific Research and Innovation Support Unit, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh Egypt

A

Abrar Mortada Abdelraheem

Pharmaceutical Chemistry Department, Faculty of Pharmacy Egyptian Russian University Badr City Egypt

I

Ibrahim Taha Radwan

Supplementary General Sciences Department, Faculty of Oral and Dental Medicine Future University in Egypt Cairo Egypt

E

Eman Darweish

Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy Egyptian Russian University Badr City Egypt

A

Abdulrahman A. Almehizia

Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University Riyadh Saudi Arabia

A

Ahmed M. Naglah

Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University Riyadh Saudi Arabia

F

Fahad A. Almehizia

Dental department Prince Mohammed bin Abdulaziz Hospital Riyadh Saudi Arabia

M

Mohamed Fares

Pharmaceutical Chemistry Department, Faculty of Pharmacy Egyptian Russian University Badr City Egypt; School of Pharmacy The University of Sydney Sydney New South Wales Australia

W

Wagdy M. Eldehna

Department of Pharmaceutical Chemistry, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh Egypt

H

Hatem A. Abdel‐Aziz

Applied Organic Chemistry Department National Research Center Dokki Egypt

Funding

University of Sydney

King Saud University Award: ORF‐RC‐2025‐0121

Cite This Article

Mohamed K. Elgohary, Mahmoud S. Elkotamy, Zainab M. Elsayed, et al. (2025). Rational Design of Triazole Hydrazide Derivatives With Imidazo[2,1‐ b ]thiazole Scaffolds as Targeted EGFR Inhibitors in NSCLC. Drug Development Research, 87(1). https://doi.org/10.1002/ddr.70211

Rational Design of Triazole Hydrazide Derivatives With Imidazo[2,1‐ b ]thiazole Scaffolds as Targeted EGFR Inhibitors in NSCLC

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