Cytotoxic Activity and Molecular Docking Studies of the Fraction Containing Ergosta-14,22-dien-3-ol (3β, 5α, and 22E) from Dysidea avara Sponges

Abstract

Background: Cancer is a global health burden, and the discovery of novel therapeutic agents remains a critical pursuit. Marine organisms, including sponges, have emerged as a promising source of structurally diverse natural products with potential anticancer properties. Objectives: In the present study, the cytotoxic activity of the fraction containing Ergosta-14,22-dien-3-ol (3β, 5α, and 22E), a steroid compound derived from Dysidea avara, was evaluated against Jurkat/E6-1 and Hek293 cells. Methods: Multiple analytical techniques, including column chromatography, TLC, and GC-MS, were used to isolate and identify the compound from marine sponges from the Persian Gulf. The XTT assay determined the cytotoxic activity and western blot for P53 expression in the Jurkat/ E6-1 cell line. The compound was also docked within the poly (ADP-ribose) polymerase-1 (PARP1) and E3 ubiquitin-protein ligase (MDM2) to investigate its potential mechanism of action. Furthermore, the pharmacological properties of the compound were predicted using PerADME, SwissADME, and Molinspiration tools. Results: The results showed that Ergosta-14,22-dien-3-ol (3β, 5α, and 22E) exhibited significant cytotoxic activity against Jurkat/E6-1 cells with an IC50 of 26.59 μg/mL. Western blotting analysis demonstrated a noticeable increase in the expression of P53 protein in cells treated with 50 and 100 µg/mL of the compound. In silico analysis revealed adequate binding energy against PARP1 and E3 MDM2 receptors. The compound also demonstrated favorable pharmacokinetic characteristics, specifically in absorption, distribution, metabolism, and excretion (ADME). Conclusions: Ergosta-14,22-dien-3-ol (3β, 5α, and 22E) has the potential to be developed as a promising anti-cancer agent.