{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T14:12:03Z","timestamp":1778335923029,"version":"3.51.4"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T00:00:00Z","timestamp":1576800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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\u2032-oxo-1\u2032-((3,4,5-trimethoxybenzylidene)amino)-1\u2032,5\u2032-dihydro-10H-spiro[acridine-9,2\u2032-pyrrole]-4\u2032-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. LD50 (lethal dose 50%) was estimated to be higher than 5000 mg\/kg. AMTAC-17 reduced the Ehrlich tumor\u2019s 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-1\u03b2, TNF-\u03b1, 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.<\/jats:p>","DOI":"10.3390\/molecules25010029","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T03:23:12Z","timestamp":1577071392000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action"],"prefix":"10.3390","volume":"25","author":[{"given":"Daiana K. Frade","family":"Silva","sequence":"first","affiliation":[{"name":"Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e2mia S.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tha\u00eds M. H.","family":"Lisboa","sequence":"additional","affiliation":[{"name":"Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael C.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Lu\u00edza de O.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6987-262X","authenticated-orcid":false,"given":"Deyse C. M.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Multicenter Postgraduate Program in Physiological Sciences, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Rodrigues-Mascarenhas","sequence":"additional","affiliation":[{"name":"Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"},{"name":"Multicenter Postgraduate Program in Physiological Sciences, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9687-0235","authenticated-orcid":false,"given":"Patricia Mirella","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A. S. Pinheiro","family":"Segundo","sequence":"additional","affiliation":[{"name":"Post Graduation Program in Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE 50670-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo O. de","family":"Moura","sequence":"additional","affiliation":[{"name":"Drug Development and Synthesis Laboratory, Department of Pharmacy, State University of Para\u00edba, Jo\u00e3o Pessoa, PB 58070-450, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina C. P.","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Department of Morphology, Federal University of Rio Grande do Norte, Natal, RN 59078-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-034X","authenticated-orcid":false,"given":"Marianna V.","family":"Sobral","sequence":"additional","affiliation":[{"name":"Post Graduation Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"},{"name":"Department of Pharmaceutical Sciences, Federal University of Paraiba, Jo\u00e3o Pessoa, PB 58051-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.1172\/JCI80007","article-title":"Immunity, inflammation, and cancer: An eternal fight between good and evil","volume":"125","author":"Shalapour","year":"2015","journal-title":"J. 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