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

Authors :
Correa WA
das Neves SC
Oliveira RJ
Kassuya CA
Navarro SD
Faustino Martins AC
Saroja B
Mitsuyasu B
Ostaciana Maia Freitas da Silveira I
Vitor N
Coelho HRS
Vilela MLB
do Nascimento VA
de Lima DP
Beatriz A
da Silva Gomes R
Source :
Chemical research in toxicology [Chem Res Toxicol] 2024 Feb 19; Vol. 37 (2), pp. 259-273. Date of Electronic Publication: 2024 Jan 06.
Publication Year :
2024

Abstract

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.

Details

Language :
English
ISSN :
1520-5010
Volume :
37
Issue :
2
Database :
MEDLINE
Journal :
Chemical research in toxicology
Publication Type :
Academic Journal
Accession number :
38183658
Full Text :
https://doi.org/10.1021/acs.chemrestox.3c00269