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

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.

Synthesis and antitumoral activity of novel analogues monastrol-fatty acids against glioma cells.

Monastrol is a small cell-permeable heterocyclic molecule that is recognized as an inhibitor of mitotic kinesin Eg5. Heterocyclic-fatty acid derivatives are a new class of compounds with a broad range of biological activities. This work describes a comparative study of the in vitro antitumoral activity of a series of new long-chain monastrol analogues against rat glioblastoma cells. The novel analogues C6-substituted monastrol and oxo-monastrol were synthesized via Biginelli multicomponent condensation of fatty ß-ketoester in good yields using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Following synthesis, their in vitro antitumoral activities were investigated. Notably, all analogues tested were active against rat glioblastoma cells. Superior activity was observed by analogues derived from palmitic and stearic fatty acid chains; these compounds were the most potent molecules, showing 13-fold higher potency than monastrol with IC50 values of 5.11 and 6.85 µM, respectively. These compounds could provide promising new lead derivatives for more potent antitumor drugs.