Aminoguanidine Hydrazone Derivatives: The Antioxidant, Antineoplastic Profile, and Interaction with ctDNA Studies

Abstract

Herein, we report the synthesis and evaluation of four aminoguanidine hydrazone derivatives with different aromatic moieties. This class of compounds presents a series of biological applications. Derivative AGH-3 with an indole nucleus offered the highest antioxidant capacity with results comparable to Trolox in 2,2-diphenyl-2-picrylhydrazyl radical (DPPH•), 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+), FeIII reduction assay (FRAP), and nitric oxide (•NO) radical scavenging assays. Furthermore, AGH-3 showed the highest antiproliferative activity against human kidney cancer cells (786-0) with concentration necessary to inhibit 50% cell growth (GI50) = 6.3 µM; additionally, in biophysical studies, AGH-3 interacted with ctDNA (biological target model) forming a fluorescent supramolecular complex with a binding constant (Kb) of 2.89 × 103 M-1 with preferentially an intercalator mechanism. The tested compounds revealed the potential of aminoguanidine hydrazones as a strategic class of compounds with multitarget biological activity.