| Autor: |
Silva DKF; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil., Duarte SS; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil., Lisboa TMH; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil., Ferreira RC; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil., Lopes ALO; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil., Carvalho DCM; Multicenter Postgraduate Program in Physiological Sciences, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil., Rodrigues-Mascarenhas S; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.; Multicenter Postgraduate Program in Physiological Sciences, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil., da Silva PM; Department of Molecular Biology, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil., Segundo MASP; Post Graduation Program in Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE 50670-901, Brazil., Moura RO; Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Paraíba, João Pessoa, PB 58070-450, Brazil., Medeiros KCP; Department of Morphology, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil., Sobral MV; Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa, PB 58051-970, Brazil.; Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa, PB 58051-970, Brazil. |
| Abstrakt: |
Tumor cells have specific features, including angiogenesis induction, cell cycle dysregulation, and immune destruction evasion. By inducing a T helper type 2 (Th2) immune response, tumor cells may favor immune tolerance within the tumor, which allows progression of cancer growth. Drugs with potential antitumor activity are the spiro-acridines, which is a promising new class of acridine compounds. Herein, the novel spiro-acridine ( E )-5'-oxo-1'-((3,4,5-trimethoxybenzylidene)amino)-1',5'-dihydro-10 H -spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-17) was synthesized and tested for antitumor effects. Toxicity evaluation was performed in mice after acute treatment (2000 mg/kg, intraperitoneally, i.p.). The Ehrlich ascites carcinoma model was used to investigate the antitumor activity of AMTAC-17 (12.5, 25, or 50 mg/kg, i.p.) after seven days of treatment. Effects on the cell cycle, angiogenesis, and inflammatory responses were investigated. LD 50 (lethal dose 50%) was estimated to be higher than 5000 mg/kg. AMTAC-17 reduced the Ehrlich tumor's total viable cancer cells count and peritumoral micro-vessels density, and induced an increase in the sub-G1 peak. Additionally, there was an increase of Th1 cytokine profile levels (IL-1β, TNF-α, and IL-12). In conclusion, the spiro-acridine compound AMTAC-17 presents low toxicity, and its in vivo antitumor effect involves modulation of the immune system to a cytotoxic Th1 profile and a reduction of tumor angiogenesis. |
