Four different Mannich base derivatives containing an aromatic/heteroaromatic propanone structure (C1 (3-(dimethylamino)-1-(thiophen-2-yl)propan-l-one hydrochloride); C2 (3-morpholino-1-(pyridin-3-yl)propan-l-one hydrochloride); C3 (3-(dimethylamino)-1-(1H-indo1-3-yl)propan-1-one hydrochloride), C4 (3-(piperidin-1-y1)-1-(pyren-lyl)propan-l-one hydrochloride)) were earlier synthesized and characterized with I-H NMR, 13 C NMR, MS, and elemental analysis. The interaction of these compounds with fish sperm double stranded DNA (fs-dsDNA) was investigated by using differential pulse voltammetry (DPV) in connection with a disposable pencil graphite electrode (PGE). After the interaction procedure, there was a meaningful decrease in the oxidation signal of the electroactive DNA base guanine due to possible intercalation and/or alkylation mechanism between these Mannich base derivatives and DNA. The features of this electrochemical assay were discussed in comparison to previous reports related to DNA targeted agents/drug candidates in the literature.