{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:47:38Z","timestamp":1760147258494,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-COBRE","award":["1P20GM109024","59\/300.112\/2015"],"award-info":[{"award-number":["1P20GM109024","59\/300.112\/2015"]}]},{"name":"FUNDECT","award":["1P20GM109024","59\/300.112\/2015"],"award-info":[{"award-number":["1P20GM109024","59\/300.112\/2015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>3-heptylidene-4,6-dimethoxy-3H-isobenzofuran-1-one (Phthalide 1) is the precursor of three resorcinol lipids that have been described as potential chemotherapeutic agents and capable of potentiating the effects of cyclophosphamide. In this study, we evaluated the genotoxic potential, cell-killing potential, and interactions with cyclophosphamide and cisplatin of phthalide 1. Twelve groups were created from 120 mice: Negative Control, cyclophosphamide (100 mg\/kg), cisplatin (6 mg\/kg), Phthalide 1 (5, 10 and 20 mg\/kg), and associations of 1 with cyclophosphamide and 1 with cisplatin. The results demonstrate that 1 increases (p &lt; 0.05) the frequency of chromosomal damage, liver and kidney cell death, and splenic phagocytosis. The association of 1 with cyclophosphamide and cisplatin demonstrated a chemopreventive effect and, therefore, a reduction (p &lt; 0.05) in the frequency of chromosomal damage. However, cell death and splenic phagocytosis did not suffer significant variations. As a result of the above, 1 has potential chemotherapeutic application and may be a candidate for developing a new generation of chemotherapeutics. In addition, it has characteristics to be used as a chemotherapy adjuvant in association with cyclophosphamide and cisplatin since it increases the frequency of cell death induced by chemotherapy. We also reported that the chemopreventive effect of 1, in association with cyclophosphamide and cisplatin, can prevent adverse effects (induction of DNA damage in non-tumor cells) without interfering with the mode of action of chemotherapy drugs and, therefore, without reducing the induction of cell death.<\/jats:p>","DOI":"10.3390\/molecules28031044","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T02:35:55Z","timestamp":1674182155000},"page":"1044","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["3-Heptylidene-4,6-Dimethoxy-3H-Isobenzofuran-1-One Is Genotoxic, Increases the Frequency of Cell Death, and Potentiates the Effects of Cyclophosphamide and Cisplatin"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3276-4198","authenticated-orcid":false,"given":"Silvia Cordeiro","family":"das Neves","sequence":"first","affiliation":[{"name":"Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79080-190, MS, Brazil"},{"name":"Graduate Programme in Health and Development in the Midwest Region, Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio Henrique","family":"de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79080-190, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willian Ayala","family":"Correa","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5647-2187","authenticated-orcid":false,"given":"Allana Cristina Faustino","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2438-6510","authenticated-orcid":false,"given":"Henrique Rodrigues Scherer","family":"Coelho","sequence":"additional","affiliation":[{"name":"Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79080-190, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo Luiz Brand\u00e3o","family":"Vilela","sequence":"additional","affiliation":[{"name":"Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valter Arag\u00e3o","family":"do Nascimento","sequence":"additional","affiliation":[{"name":"Graduate Programme in Health and Development in the Midwest Region, Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8998-9219","authenticated-orcid":false,"given":"Candida Aparecida Leite","family":"Kassuya","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Federal University of Grande Dourados, Dourados 79070-900, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6023-4867","authenticated-orcid":false,"given":"D\u00eanis Pires","family":"de Lima","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6864-6092","authenticated-orcid":false,"given":"Adilson","family":"Beatriz","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3514-3346","authenticated-orcid":false,"given":"Rodrigo Juliano","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79080-190, MS, Brazil"},{"name":"Graduate Programme in Health and Development in the Midwest Region, Medical School, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8075-9716","authenticated-orcid":false,"given":"Roberto da Silva","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e20201347","DOI":"10.1590\/0001-3765202120201347","article-title":"Straightforward synthesis of cytosporone analogs AMS35AA and AMS35BB","volume":"93","author":"Vitor","year":"2021","journal-title":"An. 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