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.