Evaluation of the antioxidant activities of fatty polyhydroquinolines synthesized by Hantzsch multicomponent reactions

Abstract

Polyhydroquinolines (PHQs) are the unsymmetrical Hantzsch derivatives of 1,4-dihydropyridines with several biological applications. In this work, new fatty 2- and 3-substituted PHQ derivatives from different fatty acids and fatty alcohol feedstocks were synthesized at good yields via a four-component reaction (4CR). The antioxidant activities of fatty PHQs were investigated using three different antioxidant methods. The experiments showed that the compounds derived from 2-nitrobenzaldehyde and fatty palmitic (C16:0) and oleic (C18:1) chains showed better antioxidant activity. This revealed that combining the ortho NO₂ group in the aromatic ring with the insertion of fatty chains in the PHQ core contributed to the antioxidant activity. However, among all the fatty PHQs tested, the fatty 2-substituted compound derived from oleyl alcohol and 2-nitrobenzaldehyde showed the highest antioxidant activity (EC₅₀, 2.11–4.69 μM), which was similar to those of the antioxidant standards butylated hydroxytoluene (EC₅₀, 1.98–6.47 μM) and vitamin E (EC₅₀, 1.19–5.88 μM). In addition, this lipophilic compound showed higher antioxidant activity than the antihypertensive drug nifedipine (EC₅₀, 49.25–126.86 μM). These results indicate that the new fatty PHQs may find novel applications as antioxidant additives.