Cytotoxic Activity Against SH-SY5Y Neuroblastoma Cells of Heterocyclic Compounds Containing gem-Dichlorocyclopropane and/or 1,3-Dioxacycloalkane Fragments

The cytotoxic properties of ethers, esters, and ketones containing gem -dichlorocyclopropane and/or 1,3-dioxacycloalkane fragments were studied in vitro using normal human embryonic kidney (HEK293) and human neuroblastoma cancer cell lines (SH-SY5Y). Compounds producing selective toxic effects on SH-SY5Y cells were identified and included 4,4-[1,2-diphenylene- bis (methylenoxymethylene)- bis (2,2-dimethyl-1,3-dioxolane) (IC 50 = 33.21 ± 1.34 μM), [3-(butoxymethyl)-2,2-dichlorocyclopropyl]benzene (IC 50 = 88.60 ± 6.93 μM), and 1,2- bis {[(2,2-dichlorocyclopropyl)methoxy]methyl}benzene (IC 50 = 90.90 ± 5.78 μM). High selectivity indices (SI) were established for 4-({[(2-chloromethyl)benzyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolane (SI = 8.03) and 4,4-[1,2-diphenylene- bis (methylenoxymethylene)]- bis (2,2-dimethyl-1,3-dioxolane) (SI = 3.01). The results allowed directions for the synthesis of new cytotoxic heterocyclic substances with gem -dichlorocyclopropane and/or 1,3-dioxacycloalkane fragments with specificity for SH-SY5Y cells to be determined.