Assessment of Cytotoxic/Antitumour Potential and in silico Study of Salazinic Acid Isolated from Parmotrema concurrens

Abstract

Introduction: Despite numerous scientific advances, cancer continues to be one of the main causes of death in the world. This situation has driven the search for promising molecules. Lichen substances have been widely described for their pharmacological potential. Objective: The present study evaluated the antitumour potential of a depsidone isolated from Parmotrema concurrens– salazinic acid (SAL) – through in vitro, in vivo and in silico studies. Methods: The molecule was isolated from the acetonic extract of the lichen and recrystallized in acetone. The macrophage J774, sarcoma-180 and MDA-MB-231 cell lines were used for the MTT cytotoxicity assay. The antitumor assay used a murine model (Swiss albino mice) with sarcoma-180. The animals were treated for seven consecutive days with doses of SAL (25 and 50 mg/kg) and 5-fluorouracil (20 mg/kg). Results: Its purity was determined using high-performance liquid chromatography (94%), and its structure was confirmed by H1 and C13 nuclear magnetic resonance. SAL was not considered toxic to cancer cell lines, showing cell viability rates of 79.49 ± 4.15% and 86.88 ± 1.02% for sarcoma-180 and MDA-MB-231, respectively. The tumour inhibition rate was greater than 80% in the animals treated with SAL and 65% for those that received 5-fluorouracil. Simulations of molecular dynamics to estimate the flexibility of the interactions between human thymidylate synthase and derivatives of SAL and 5-fluorouracil revealed that SAL exhibited greater enzymatic interaction capacity, with highly favourable energy, compared to 5-fluorouracil. Conclusion: The present results demonstrate the potential of salazinic acid as a tumour inhibition agent.