Tehran University of Medical Sciences

Science Communicator Platform

Share By
Design, Synthesis, and Bioactivity Assessment of Highly Potent Isatin-Based Small-Molecules Bearing 3-Hydrazineyl-6-Aryl-1,2,4-Triazine Moieties As Potential C-Met Targeting Anticancer Agents Publisher



Zakeri Khatir Z ; Alipour A ; Mortazavi M ; Tavakkoli M ; Irannejad H ; Foroumadi A ; Firuzi O ; Valipour M
Authors

Source: Bioorganic Chemistry Published:2026


Abstract

The present study reports the design, synthesis, and biological evaluation of 25 novel isatin-based small molecules bearing 3-hydrazineyl-6-aryl-1,2,4-triazine motifs, generated through anticancer-scaffold hybridization and structure-guided modification of a c-MET inhibitor hit compound 3a . The antiproliferative properties of the target compounds ( E1–25 ) were assessed against three cancer cell lines comprising EBC-1 (c-MET-amplified NSCLC), SUIT-2 (pancreatic ductal adenocarcinoma), MDA-MB-231 (triple-negative breast adenocarcinoma) as well as non-malignant fibroblast cells NIH-3T3. Several derivatives exhibited pronounced antiproliferative activity, with IC50 values ranging from the sub-micromolar level to as low as 11 nM, while showing reduced effects on non-cancerous cells. Further analysis of the effects of highly active compounds E20 , E21 , E23 and E24 on cell cycle and cancer cell growth in 3-dimensional spheroid cultures showed that these derivatives induce apoptosis and significantly inhibit the growth of cancer cells in the 3D environment. Molecular docking simulations revealed that the evaluated compounds adopt a linear binding mode within the c-MET active site, in contrast to the U-shaped binding pattern characteristic of class Ib c-MET inhibitors. Overall, the newly developed isatin-1,2,4-triazine hybrids exhibited potent anticancer activity, highlighting their potential as promising lead structures for future anticancer drug development. © 2026 Elsevier Inc.
Related Docs
View other Related Docs
1. Design of Chiral 2-Oxazoline-Based Amino Acid Bioconjugates As Anticancer Agents: Synthesis, in Vitro Anticancer Activity, Admet Prediction With Molecular Docking and Molecular Dynamic Simulation Insights, Archives of Biochemistry and Biophysics (2025)
2. Anticancer Properties of N-Alkyl-2, 4-Diphenylimidazo [1, 2-A] Quinoxalin-1-Amine Derivatives; Kinase Inhibitors, Bioorganic Chemistry (2019)
3. Design and Synthesis of Bmh-21-Like Quinazolinone Derivatives As Potential Anti-Cancer Agents, Journal of Molecular Structure (2024)
Experts (# of related papers)
View all Related Experts
Mohsen Amini (7)
Alireza Foroumadi (7)
Other Related Docs
4. New Phosphoramides Containing 2-Amino-1,4-Naphthaquinone Moiety As Anticancer and Antibacterial Agents: Experimental and Theoretical Evaluations, Process Biochemistry (2023)
5. Coumarin Derivatives As Potential Anticancer Agents: Synthesis, Antiproliferative Activity, Apoptosis, and Molecular Docking Studies, Results in Chemistry (2025)
6. Design, Synthesis, Anticancer Properties, and Molecular Dynamics of New Quinazolinonethioacetohydrazide-1,2,3-Triazoles, Chemistry and Biodiversity (2025)
7. Novel Quinazolin-4(3H)-One Linked to 1,2,3-Triazoles: Synthesis and Anticancer Activity, Chemical Biology and Drug Design (2018)
8. A Review on Zinc, Cadmium, and Mercury Complexes With Anticancer Activity, Inorganic Chemistry Communications (2024)
9. Synthesis, Molecular Docking Study, and Cytotoxic Activity of 1,3,5-Triaryl Pyrazole Derivatives, Letters in Drug Design and Discovery (2016)
10. Design, Synthesis, and Cytotoxic Evaluation of Quinazoline Derivatives Bearing Triazole-Acetamides, Heliyon (2023)
11. Design, Synthesis and Anticancer Evaluation of Novel Series of Indibulin Analogues, Medicinal Chemistry (2019)
12. Mono- and Bis-Pyrazolophthalazines: Design, Synthesis, Cytotoxic Activity, Dna/Hsa Binding and Molecular Docking Studies, Bioorganic and Medicinal Chemistry (2021)
13. Green Synthesis and Anticancer Evaluation of Novel Chrysin Hydrazone Derivatives, Polycyclic Aromatic Compounds (2023)
14. Synthesis and Biological Evaluation of 4-Amino-5-Cinnamoylthiazoles As Chalcone-Like Anticancer Agents, European Journal of Medicinal Chemistry (2018)
15. Triarylpyrazole Derivatives As Potent Cytotoxic Agents; Synthesis and Bioactivity Evaluation Pyrazole Derivatives As Anticancer Agent, Drug Research (2021)
16. Design, Synthesis and Biological Evaluation of Novel Diaryl Pyrazole Derivatives As Anticancer Agents, Letters in Organic Chemistry (2020)
17. Novel Quinazolines Bearing 1,3,4-Thiadiazole-Aryl Urea Derivative As Anticancer Agents: Design, Synthesis, Molecular Docking, Dft and Bioactivity Evaluations, BMC Chemistry (2024)
18. Synthesis, Biological Evaluation, and in Silico Study of Novel Coumarin-Quinazoline Analogs As Potential Anti-Angiogenesis Agents, Results in Chemistry (2024)
19. Synthesis, Biological Evaluation, and Docking Analysis of Novel Benzimidazole-Triazole Hybrids As Potential Anticancer Agents, RSC Advances (2025)
20. Design, Synthesis, Spectroscopic Characterization, in Vitro Tyrosinase Inhibition, Antioxidant Evaluation, in Silico and Kinetic Studies of Substituted Indole-Carbohydrazides, Bioorganic Chemistry (2022)