RESUMEN

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: AMTAC-06 did not induce toxicity on zebrafish and mice (LD50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G1 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-1ß 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.

Asunto(s)

Acridinas/farmacología , Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Factores Inmunológicos/farmacología , Compuestos de Espiro/farmacología , Acridinas/química , Inhibidores de la Angiogénesis/química , Animales , Antineoplásicos/química , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Factores Inmunológicos/química , Inmunomodulación/efectos de los fármacos , Ratones , Estructura Molecular , Compuestos de Espiro/química , Ensayos Antitumor por Modelo de Xenoinjerto , Pez Cebra