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2000
Volume 32, Issue 25
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X
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Abstract

Background

Indole is considered the most promising scaffold for anticancer drug design due to its high bioavailability, unique chemical properties, and broad spectrum of pharmacological action.

Objective

Twelve novel thiazole-containing the 5-fluoro-1,3-dihydro-2H-indol-2-one derivatives as sunitinib analogs were designed and synthesized, and their anticancer activity was evaluated against the NCI-60 cancer cell lines.

Methods

The thiazole-contained 5-fluoro-1,3-dihydro-2H-indol-2-one derivatives were synthesized using Knoevenagel condensation of 1,3-thiazole-5-carboxylic acid . Their anticancer activities were evaluated by NCI-60 one-dose screen assay. The molecular docking studies were performed using AutoDock tools and the AutoDock Vina programs. The ADMETlab 2.0 web server predicted the physicochemical properties of compounds.

Results

Among the synthesized new 5-fluoro-2-oxindole derivatives, compound demonstrated high antitumor activity (GI>70%) against eight types of cancer: leukemia, breast cancer, ovarian cancer, lung cancer, melanoma, CNS cancer, renal cancer, and colon cancer. The most activity was observed against breast cancer (T-47D, GI=96.17%), lung cancer (HOP-92, GI=95.95%), ovarian cancer (NCI/ADR-RES, GI=95.13%), and CNS cancer (SNB-75, GI=89.91%). The molecular docking results of compound demonstrated the possibility of inhibiting VEGF2 receptors as his potential anticancer mechanism. The physicochemical properties predicted for compounds and showed positive results.

Conclusion

Compound 3g demonstrated high NCI-60 anticancer activity against nine cancer types and showed cell growth inhibition against leukemia, CNS, and breast cancer at 6 - 31% higher than Sunitinib, and may represent the basis for further modification of the thiazole-containing analogs of the anticancer drug Sunitinib.

© 2025 The Author(s). Published by Bentham Science Publishers. 
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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Design, Synthesis, and Antitumor Potential of New Thiazole-contained 5-Fluoro-2-Oxindole Derivatives as Sunitinib Analogues
Curr. Med. Chem. 32, 5279 (2025); https://doi.org/10.2174/0109298673346427241016100726
/content/journals/cmc/10.2174/0109298673346427241016100726
/content/journals/cmc/10.2174/0109298673346427241016100726
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  • Article Type:     Research Article
Keyword(s): 5-Fluoro-2-oxindole; anticancer agents; cancer; sunitinib analogues; thiazole; VEGFR2

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