3,4,3′-Tri-O-methylellagic acid as an anticancer agent: in vitro and in silico studies

We report a natural product compound isolated from Syzygium polycephalum known as 3,4,3′-tri-O-methylellagic acid (T-EA) as a candidate drug for cancer treatment. The characterization of the isolated T-EA compound was carried out using various spectroscopic methods. The in vitro evaluation showcased the inhibition activity of T-EA towards the T47D and HeLa cell lines with EC₅₀ values of 55.35 ± 6.28 μg mL⁻¹ and 12.57 ± 2.22 μg mL⁻¹, respectively. Meanwhile, the in silico evaluation aimed to understand the interaction of T-EA with enzymes responsible for cancer regulation at the molecular level by targeting the hindrance of cyclin-dependent kinase 9 (CDK9) and sirtuin 1 (SIRT1) enzymes. T-EA showed a binding free energy towards the SIRT1 protein of ΔG_{bind (MM-GBSA)}: −30.98 ± 0.25 kcal mol⁻¹ and ΔG_{bind (MM-PBSA)}: −24.07 ± 0.30 kcal mol⁻¹, while that of CDK9 was ΔG_{bind (MM-GBSA)}: −29.50 ± 0.22 kcal mol⁻¹ and ΔG_{bind (MM-PBSA)}: −25.87 ± 0.40 kcal mol⁻¹. The obtained results from this research could be considered as important information on 3,4,3′-tri-O-methylellagic acid as a drug to treat cervical and breast cancers.