Diterpenoids profile of the marine sponge Chelonaplysilla erecta and candidacy as potential antitumor drugs investigated by molecular docking and pharmacokinetic studies

Abstract

The Chelonaplysilla genus possesses a numerous bioactive diterpenes with anti-inflammatory and cytotoxic effects. The current study aimed to assess the chemical composition of C. erecta crude extract (CECE) based on its metabolomic profile that has been integrated with neural network-based virtual screening and molecular docking using liquid chromatography with high resolution mass spectrometry (LCHR-MS). In addition to the estimation of the antitumor activity of the same extract via anti-interleukin-17A (IL-17) action, along with its formulated spanlastics preparation. The CECE markedly displayed growth inhibition for HepG-2 cells at IC₅₀ value 16.5 ± 0.8 μg/mL, whereas the spanlastic formulation revealed more eminent antitumor effect against Caco-2 cells (IC₅₀ = 2.8 ± 0.03 μg/mL). Among the dereplicated compounds, macfarlandin F (16) and pourewanone (25) demonstrated the highest potential with co-crystallized ligand 63 O within the active site of IL-17A in molecular docking studies. These findings rationalized the antitumor mechanism of marine organism for future chemotherapeutic applications.

Keywords: Chelonaplysilla erecta; antitumor; metabolomic; molecular docking; spanlastics preparation.