Benzimidazole-dioxoisoindoline conjugates as dual VEGFR-2 and FGFR-1 inhibitors: design, synthesis, biological investigation, molecular docking studies and ADME predictions.

ABSTRACT: In this investigation, a new series of benzimidazole-dioxo(benzo)isoindoline hybrids 8a-o were rationally designed and synthesized. All the synthesized hits 8a-o were investigated for their VEGFR-2 inhibitory activity at 10 μM. The conjugates 8l and 8m demonstrated potent inhibitory activity of 87.61 and 80.69%, respectively. Further evaluation of 8l and 8m on FGFR-1 at 10 μM demonstrated % inhibition = 84.20 and 76.83%, respectively. Investigation of the growth inhibitory activity of the synthesized hits on NCI cancer cell lines showed that the benzimidazole-dioxobenzoisoindoline hybrid 8m exhibits the highest antiproliferative activity. It displayed growth inhibitory activity reaching 89.75%. Examination of the effect of 8m on the cell cycle of MCF7 cell line revealed its ability to indu

SUBMITTER: Abdel-Mohsen HT 

PROVIDER: S-EPMC11391345 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature