Anti-Angiogenic and Anti-Proliferative Activities of 5-Bromo-N-(2,5-Dioxopyrrolidin-1-Yl)-1H-Indole-2-Carboxamide.

Abstract

Background: Angiogenesis has long been a key focus for drug designers aiming to develop therapies targeting diseases associated with this physiological process. A newly synthesized compound from the University of Baghdad was evaluated for its ability to inhibit blood vessel growth. The objective of this study was to investigate the anti-angiogenic activity of 5-bromo-N-(2,5-dioxopyrrolidin-1-yl)-1H-indole-2-carboxamide using an ex vivo rat aorta model.

Methods: An anti-angiogenesis assay was employed to assess the dose-response relationship and to determine the concentration that inhibits 50% of blood vessel growth (IC50). The anti-proliferative effect on endothelial cells was assessed using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Additionally, the free radical scavenging activity of the compound was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The anti-proliferative activity against the A549 lung cancer cell line was also investigated.

Results: The compound demonstrated significant anti-angiogenic activity with an IC50 of 15.4 µg/mL. The IC50 on the HUVEC cell line was 5.6 µg/mL. Its free radical scavenging activity was measured at 99.6 µg/mL. Furthermore, the compound significantly inhibited the proliferation of the A549 lung cancer cell line, with an IC50 of 14.4 µg/mL.

Conclusion: The findings suggest that 5-bromo-N-(2,5-dioxopyrrolidin-1-yl)-1H-indole-2-carboxamide possesses notable anti-angiogenic activity and a significant anti-proliferative effect on HUVEC cells, potentially linked to its strong free radical scavenging capacity. Moreover, it effectively inhibited the proliferation of lung cancer cells.