Design, Synthesis, and Antitumor Potential of New Thiazole--contained 5-Fluoro-2-Oxindole Derivatives as Sunitinib Analogues.

Autor:	Semenyuta I; Department of chemistry of natural compounds, V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, Kyiv, 02094, Ukraine., Los O; Department of chemistry of bioactive nitrogen-containing heterocyclic bases, V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, Kyiv, 02094, Ukraine., Sinenko V; Department of chemistry of bioactive nitrogen-containing heterocyclic bases, V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, Kyiv, 02094, Ukraine., Zhirnov V; Department of chemistry of bioactive nitrogen-containing heterocyclic bases, V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, Kyiv, 02094, Ukraine., Potikha L; Department of chemistry of bioactive nitrogen-containing heterocyclic bases, V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, Kyiv, 02094, Ukraine.; Department of chemistry, Taras Shevchenko National University, Kyiv, 01601, Ukraine., Kobzar O; Department of mechanisms of bioorganic reactions, V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, Kyiv, 02094, Ukraine., Brovarets V; Department of chemistry of bioactive nitrogen-containing heterocyclic bases, V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, Kyiv, 02094, Ukraine.
Jazyk:	angličtina
Zdroj:	Current medicinal chemistry [Curr Med Chem] 2024 Nov 04. Date of Electronic Publication: 2024 Nov 04.
DOI:	10.2174/0109298673346427241016100726
Abstrakt:	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. Method: 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 1. 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 3g 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 3g demonstrated the possibility of inhibiting VEGF2 receptors as his potential anticancer mechanism. The physicochemical properties predicted for compounds 3f and 3g showed positive results. Conclusion: Compound 3g demonstrated high in vitro 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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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