{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:08:56Z","timestamp":1779242936816,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"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>The antitumor effects of thiophene and acridine compounds have been described; however, the clinical usefulness of these compounds is limited due to the risk of high toxicity and drug resistance. The strategy of molecular hybridization presents the opportunity to develop new drugs which may display better target affinity and less serious side effects. Herein, 2-((6-Chloro-2-methoxy-acridin-9-yl)amino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]-thiophene-3-carbonitrile (ACS03), a hybrid thiophene\u2013acridine compound with antileishmanial activity, was tested for toxicity and antitumor activity. The toxicity was evaluated in vitro (on HaCat and peripheral blood mononuclear cells) and in vivo (zebrafish embryos and acute toxicity in mice). Antitumor activity was also assessed in vitro in HCT-116 (human colon carcinoma cell line), K562 (chronic myeloid leukemic cell line), HL-60 (human promyelocytic leukemia cell line), HeLa (human cervical cancer cell line), and MCF-7 (breast cancer cell line) and in vivo (Ehrlich ascites carcinoma model). ACS03 exhibited selectivity toward HCT-116 cells (Half maximal inhibitory concentration, IC50 = 23.11 \u00b1 1.03 \u00b5M). In zebrafish embryos, ACS03 induced an increase in lactate dehydrogenase, glutathione S-transferase, and acetylcholinesterase activities. The LD50 (lethal dose 50%) value in mice was estimated to be higher than 5000 mg\/kg (intraperitoneally). In vivo, ACS03 (12.5 mg\/kg) induced a significant reduction in tumor volume and cell viability. In vivo antitumor activity was associated with the nitric oxide cytotoxic effect. In conclusion, significant antitumor activity and weak toxicity were recorded for this hybrid compound, characterizing it as a potential anticancer compound.<\/jats:p>","DOI":"10.3390\/molecules25010064","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T10:28:43Z","timestamp":1577183323000},"page":"64","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Toxicity and Antitumor Activity of a Thiophene\u2013Acridine Hybrid"],"prefix":"10.3390","volume":"25","author":[{"given":"Tha\u00eds","family":"Lisboa","sequence":"first","affiliation":[{"name":"Postgraduate Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, 58051-970 Jo\u00e3o Pessoa, Para\u00edba, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiana","family":"Silva","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, 58051-970 Jo\u00e3o Pessoa, Para\u00edba, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e2mia","family":"Duarte","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, 58051-970 Jo\u00e3o Pessoa, Para\u00edba, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, 58051-970 Jo\u00e3o Pessoa, Para\u00edba, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camyla","family":"Andrade","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, 58051-970 Jo\u00e3o Pessoa, Para\u00edba, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Luiza","family":"Lopes","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Bioactive Natural and Synthetic Products, Federal University of Para\u00edba, 58051-970 Jo\u00e3o Pessoa, Para\u00edba, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory for Risk Assessment of Novel Technologies, Department of Molecular Biology, Federal University of Paraiba, Campus I, 58051-900 Jo\u00e3o Pessoa, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5438-1919","authenticated-orcid":false,"given":"Davi","family":"Farias","sequence":"additional","affiliation":[{"name":"Laboratory for Risk Assessment of Novel Technologies, Department of Molecular Biology, Federal University of Paraiba, Campus I, 58051-900 Jo\u00e3o Pessoa, 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