Weight loss effects of quaternary salts of 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles; structure–activity relationships

摘要: Quaternary salt analogues based on the DNA minor groove binder and adenine N3 alkylating agent 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indole (aminoCBI) show remarkable effects body weight of mice (a long-term failure to gain relative matched controls with no loss appetite or perceptible deterioration in health) following administration a single (non-toxic) dose between about 0.5-5 μmol/kg. The nature quaternizing group was not important, but related hydroxyCBI analogue much less effective. Compounds where chloro replaced by hydrogen hydroxy (thus abrogating capability) showed control activity. It is speculated, other studies, that marked effect due inhibition bile flow into intestine reduced absorption triglycerides, together accelerated cell death spleen white adipose tissues drug accumulation there. This class compound may serve as interesting tools for further study these phenomena.