N-(2-ozoazepan-3-yl)-pyrrolidine-2-carboxamide, a novel Octopus vulgaris ink-derived metabolite, exhibits a pro-apoptotic effect on A549 cancer cell line and inhibits pro-inflammatory markers

Abstract

This research aimed to chemically synthesize and evaluate the antiproliferative and anti-inflammatory potential of ozopromide (OPC), a novel compound recently isolated from O. vulgaris ink. After chemical synthesis, OPC structural characterization was confirmed by COSY2D, FTIR, and C-/H-NMR. OPC inhibited the growth of human breast (MDA-MB-231), prostate (22Rv1), cervix (HeLa), and lung (A549) cancerous cells, being the highest effect on the latter (IC₅₀: 53.70 μM). As confirmed by flow cytometry, OPC induced typical apoptosis-derived morphological features on A549 cells, mostly at early and late apoptosis stages. OPC generated a dose-dependent effect inhibiting IL-6 and IL-8 on LPS-stimulated peripheral mononuclear cells (PBMCs). A major affinity of OPC to Akt-1 and Bcl-2 proteins in silico agreed with the observed pro-apoptotic mechanisms. Results suggested that OPC has the potential to alleviate inflammation and be further studied for anticancer activity. Marine-derived food products such as ink contains bioactive metabolites exhibiting potential health benefits.

Keywords: Anti-inflammatory; Cytokines; Octopus vulgaris; Ozopromide (OPC); Pro-apoptotic.