Structure-activity relationships study of N-ethylene glycol-comprising alkyl heterocyclic carboxamides against A549 lung cancer cells.

Abstract

Aim: Certain cancer cells depend on oxidative phosphorylation for survival; thus, inhibiting this process may be a promising treatment strategy. This study explored the structure-activity relationships of the mitochondrial inhibitor N-ethylene glycol-comprising alkyl thiophene-3-carboxamide 3.Methods & results: We synthesized and evaluated 13 analogs (5a-m) with different ethylene glycol units, heterocycles and connecting groups for their growth-inhibitory effects on A549 non-small cell lung cancer cells. We found that increasing the number of ethylene glycol units significantly enhanced inhibitory activity. Some analogs activated adenosine monophosphate-activated protein kinase, similar to 3. Notably, analog 5e, which contains tetraethylene glycol units, significantly inhibited tumor growth in vivo.Conclusion: Analog 5 may be a potential therapeutic agent for non-small cell lung cancer treatment.