Cytotoxicity and Selectivity of Synthetic Peptides Derived from Odontomachus chelifer Venom Against Prostate and Melanoma Cell Lines

Cancer represents a serious global public health problem, demanding the continuous search for novel therapeutic agents with high antitumor efficacy and reduced toxicity. Venoms from ants of the genus Odontomachus are promising sources of bioactive peptides, whose pharmacological properties remain poorly explored. This study evaluated the in vitro cytotoxic potential and selectivity index (SI) of three synthetic peptides (P1, P2, and P3), derived from Odontomachus chelifer venom, against four cell lines: non-tumorigenic human prostate (PNT-2), human prostate adenocarcinoma (PC3), murine fibroblasts (NIH3T3), and murine melanoma (B16F10). Cells were treated with serial dilutions of the peptides for 24 h, and cell viability was quantified using the resazurin reduction assay (570/600 nm). Half-maximal inhibitory concentration (IC₅₀) values were determined using GraphPad Prism, and the SI was calculated in Microsoft Excel as the ratio between the IC₅₀ of the non-tumorigenic cell line and that of the tumor cell line. In the prostate models, IC₅₀ values for PNT-2 were 240.9 µM (P1), 241.4 µM (P2), and 227.6 µM (P3), and for PC-3 they were 228.4 µM (P1), 226.5 µM (P2), and 249.0 µM (P3), resulting in SI values of 1.05, 1.07, and 0.91, respectively. In fibroblasts, IC₅₀ values were 248.2 µM (P1), 221.2 µM (P2), and 243.1 µM (P3), and for B16F10 they were 210.2 µM (P1), 182.4 µM (P2), and 191.9 µM (P3), with SI values of 1.18 (P1), 1.21 (P2), and 1.26 (P3). Assays were performed in independent quadruplicates. High concentrations (>180 µM) were required to reduce viability by 50% in all cell lines. Thus, peptides P1, P2, and P3 showed low cytotoxicity and low selectivity toward the tumor cell lines evaluated. Although their direct chemotherapeutic potential is limited under the conditions tested, these results provide a baseline for the design of analogs with higher net charge and amphipathicity, and for the investigation of other biological activities.