Chemotherapeutic Mechanism of Action of the Synthetic Resorcinolic Methyl 3,5-dimethoxy-2-octanoylbenzoate.
Willian Ayala CorreaSilvia Cordeiro das NevesRodrigo Juliano OliveiraCândida A KassuyaStephanie D NavarroAllana Cristina Faustino MartinsBaby SarojaBarbara MitsuyasuIngridhy Ostaciana Maia Freitas da SilveiraNeimar VitorHenrique Rodrigues Scherer CoelhoMarcelo L B VilelaValter A do NascimentoDênis Pires de LimaAdilson BeatrizRoberto da Silva GomesPublished in: Chemical research in toxicology (2024)
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.
Keyphrases
- cell death
- growth factor
- oxidative stress
- molecular docking
- copy number
- circulating tumor
- recombinant human
- dna damage
- cell free
- single molecule
- molecular dynamics simulations
- cell cycle arrest
- high throughput
- early stage
- low dose
- nucleic acid
- fatty acid
- emergency department
- genome wide
- gene expression
- risk assessment
- human health
- high dose
- cell proliferation
- dna methylation
- climate change
- drug induced
- small molecule