Chemotherapeutic Mechanism of Action of the Synthetic Resorcinolic Methyl 3,5-dimethoxy-2-octanoylbenzoate.

Autor: Correa WA; Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil., das Neves SC; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79080-190, Brazil.; Graduate Program in Health and Development in the Midwest Region, Medical School, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil., Oliveira RJ; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79080-190, Brazil.; Graduate Program in Health and Development in the Midwest Region, Medical School, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil., Kassuya CA; School of Health Sciences, Federal University of Grande Dourados, Dourados, Mato Grosso do Sul 79804-970, Brazil., Navarro SD; Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil.; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79080-190, Brazil., Faustino Martins AC; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58102, United States., Saroja B; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58102, United States., Mitsuyasu B; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58102, United States.; Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo 18618-689, Brazil., Ostaciana Maia Freitas da Silveira I; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58102, United States., Vitor N; Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil., Coelho HRS; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), Medical School, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79080-190, Brazil., Vilela MLB; Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil., do Nascimento VA; Graduate Program in Health and Development in the Midwest Region, Medical School, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil., de Lima DP; Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil., Beatriz A; Institute of Chemistry, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil., da Silva Gomes R; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58102, United States.
Jazyk: angličtina
Zdroj: Chemical research in toxicology [Chem Res Toxicol] 2024 Feb 19; Vol. 37 (2), pp. 259-273. Date of Electronic Publication: 2024 Jan 06.
DOI: 10.1021/acs.chemrestox.3c00269
Abstrakt: Resorcinolic lipids are described as potential examples of selective chemotherapeutic adjuvants that can enhance the effects of cyclophosphamide ( CYC ) while promoting cell death without causing DNA damage. Therefore, the current study attempted to describe how the resorcinolic lipid methyl 3,5-dimethoxy-2-octanoylbenzoate ( AMS35BB ) interacted with DNA (DNA docking) and how this compound affected genetic toxicology models and other biological characteristics when combined with CYC . We observed that AMS35BB , used alone (7.5 and 10 mg/kg), increases the frequency of genomic damage (comet assay) but not chromosomal damage (micronuclei assay), lowers phagocytosis, and promotes cell death in Swiss male mice. When used in association with CYC , AMS35BB can reduce the risk of genomic damage by up to 33.8% as well as chromosomal damage, splenic phagocytosis, cell death, and lymphocyte frequency. Molecular docking showed that AMS35BB had a higher affinity than the active metabolite of CYC for binding to the DNA double helix major groove. As a result, AMS35BB has the potential to be both an adjuvant when used in association with CYC and a therapeutic candidate for the development of a selective chemotherapeutic drug.
Databáze: MEDLINE