biostudies-literatureElwan APrincess Nourah bint Abdulrahman University ResearchersPrincess Nourah bint Abdulrahman University5047https://www.ebi.ac.uk/biostudies/studies/S-EPMC9370530biostudies-literatureUnknown27(15)This work is one of our efforts to discover potent anticancer agents. We modified the most promising derivative of our previous work concerned with the development of VEGFR-2 inhibitor candidates. Thirteen new compounds based on benzoxazole moiety were synthesized and evaluated against three human cancer cell lines, namely, breast cancer (MCF-7), colorectal carcinoma (HCT116), and hepatocellular carcinoma (HepG2). The synthesized compounds were also evaluated against VEGFR-2 kinase activity. The biological testing fallouts showed that compound <b>8d</b> was more potent than standard sorafenib. Such compound showed IC₅₀ values of 3.43, 2.79, and 2.43 µM against the aforementioned cancer cell lines, respectively, compared to IC₅₀ values of 4.21, 5.30, and 3.40 µM reported for sorafenib. Compound <b>8d</b> also was found to exert exceptional VEGFR-2 inhibition activity with an IC₅₀ value of 0.0554 μM compared to sorafenib (0.0782 μM). In addition, compound <b>8h</b> revealed excellent cytotoxic effects with IC₅₀ values of 3.53, 2.94, and 2.76 µM against experienced cell lines, respectively. Furthermore, compounds <b>8a</b> and <b>8e</b> were found to inhibit VEGFR-2 kinase activity with IC₅₀ values of 0.0579 and 0.0741 μM, exceeding that of sorafenib. Compound <b>8d</b> showed a significant apoptotic effect and arrested the HepG2 cells at the pre-G1 phase. In addition, it exerted a significant inhibition for TNF-α (90.54%) and of IL-6 (92.19%) compared to dexamethasone (93.15%). The molecular docking studies showed that the binding pattern of the new compounds to VEGFR-2 kinase was similar to that of sorafenib.Molecules (Basel, Switzerland)Modified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative Evaluation.PMC9370530PNURSP2022R116Abdallah AEDahab MAMehany ABMElkady HMahdy HAElwan AAlsfouk AANabeeh AAdel MElkaeed EBTaghour MSEissa IHfalseModified Benzoxazole-Based VEGFR-2 Inhibitors and Apoptosis Inducers: Design, Synthesis, and Anti-Proliferative Evaluation.This work is one of our efforts to discover potent anticancer agents. We modified the most promising derivative of our previous work concerned with the development of VEGFR-2 inhibitor candidates. Thirteen new compounds based on benzoxazole moiety were synthesized and evaluated against three human cancer cell lines, namely, breast cancer (MCF-7), colorectal carcinoma (HCT116), and hepatocellular carcinoma (HepG2). The synthesized compounds were also evaluated against VEGFR-2 kinase activity. The biological testing fallouts showed that compound <b>8d</b> was more potent than standard sorafenib. Such compound showed IC₅₀ values of 3.43, 2.79, and 2.43 µM against the aforementioned cancer cell lines, respectively, compared to IC₅₀ values of 4.21, 5.30, and 3.40 µM reported for sorafenib. Compound <b>8d</b> also was found to exert exceptional VEGFR-2 inhibition activity with an IC₅₀ value of 0.0554 μM compared to sorafenib (0.0782 μM). In addition, compound <b>8h</b> revealed excellent cytotoxic effects with IC₅₀ values of 3.53, 2.94, and 2.76 µM against experienced cell lines, respectively. Furthermore, compounds <b>8a</b> and <b>8e</b> were found to inhibit VEGFR-2 kinase activity with IC₅₀ values of 0.0579 and 0.0741 μM, exceeding that of sorafenib. Compound <b>8d</b> showed a significant apoptotic effect and arrested the HepG2 cells at the pre-G1 phase. In addition, it exerted a significant inhibition for TNF-α (90.54%) and of IL-6 (92.19%) compared to dexamethasone (93.15%). The molecular docking studies showed that the binding pattern of the new compounds to VEGFR-2 kinase was similar to that of sorafenib.2022-01-01T00:00:00Z2022 Aug2026-04-08T09:47:06.718Z2025-04-06T09:25:29.855ZS-EPMC93705303595699710.3390/molecules27155047