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Evaluation of new 5-benzylidenethiazolidin-2,4-dione derivatives linked to nitric oxide donor oxime moiety as VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative assessment and studies.

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Future medicinal chemistry 📖 저널 OA 72.5% 2025: 6/6 OA 2026: 23/34 OA 2025~2026 2026 Vol.18(8) p. 943-960
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Abd El-Hameed AM, Ahmed NM, Fadaly WAA, Zidan TH, El-Manawaty M, Magdy F

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[AIM] Approaching VEGFR-2 blockers, two novel series of 5-benzylidenethiazolidine-2,4-dione and were synthesized.

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APA Abd El-Hameed AM, Ahmed NM, et al. (2026). Evaluation of new 5-benzylidenethiazolidin-2,4-dione derivatives linked to nitric oxide donor oxime moiety as VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative assessment and studies.. Future medicinal chemistry, 18(8), 943-960. https://doi.org/10.1080/17568919.2026.2642678
MLA Abd El-Hameed AM, et al.. "Evaluation of new 5-benzylidenethiazolidin-2,4-dione derivatives linked to nitric oxide donor oxime moiety as VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative assessment and studies.." Future medicinal chemistry, vol. 18, no. 8, 2026, pp. 943-960.
PMID 41837691 ↗

Abstract

[AIM] Approaching VEGFR-2 blockers, two novel series of 5-benzylidenethiazolidine-2,4-dione and were synthesized.

[METHODS] Screening against and cancer cell lines.

[RESULTS] Derivatives and employed cytotoxicity against (22.75% to 55.30%) (Doxorubicin = 87.6%). Compound presented IC of 90.70 µM for (Doxorubicin = 32.36 µM). Concerning HCT-116 cell line, compounds 17d, 17e, and 17f haunted % inhibition (59.15% to 83.76%) (Doxorubicin = 96.8%). Besides, 17d, 17e, and 17f exhibited IC of 36.11, 54.50, and 67.22 µM, respectively (Doxorubicin = 21.27 µM). Also, compounds and disclosed safety outlines alongside normal cell IC (109.5 to 165 µM) (Doxorubicin = 38.51 µM). Compound arrested cell cycle at G2/M stage. Compounds released NO potentiating anti-cancer activity. , and inhibit VEGFR-2 (IC of 50.0 nM, 23.0 nM, and 111.0 nM, respectively) and sunitinib (84.0 nM). Western blot results displayed compound notable inhibition of the VEGFR-2/Akt/ERK axis. Docking studies revealed derivatives 17d-f docking score of -8.3 to -8.9 Kcal/Mol comparable to sunitinib and sorafenib.

[CONCLUSION] The present work flags the approach for advanced expansion of powerful nitric oxide donor offshoots as VEGFR-2 inhibitors.

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