Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions
Sâmia Sousa Duarte, Daiana Karla Frade Silva, Thaís Mangeon Honorato Lisboa, Rawny Galdino Gouveia, Rafael Carlos Ferreira, Ricardo Olímpio de Moura, Jamire Muriel da Silva, Éssia de Almeida Lima, Sandra Rodrigues‐Mascarenhas, Patrícia Mirella da Silva, Davi Felipe Farias, Juliana Alves da Costa Ribeiro Souza, Karina Carla de Paula Medeiros, Juan Carlos Ramos Gonçalves, Marianna Vieira Sobral
Abstract
BACKGROUND/AIM: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound. MATERIALS AND METHODS: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated. RESULTS: peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an anti-angiogenic action, possibly dependent on the cytokine modulation (TNF-α, IL-1β and IFN-γ). No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals. CONCLUSION: AMTAC-06 has low toxicity and a significant antitumor activity.