Anti-tyrosinase, anti-cholinesterase and cytotoxic activities of extracts and phytochemicals from the Tunisian Citharexylum spinosum L.: Molecular docking and SAR analysis

Abstract

Previously phytochemical investigations carried out on the flowers and trunk bark extracts of Citharexylum spinosum L. tree, allowed the isolation of twenty molecules belonging to several families of natural substances [triterpene acids, iridoid glycosides, phenylethanoid glycosides, 8,3'-neolignan glycosides, together with other phenolic compounds]. In the present work, a biological evaluation (anti-tyrosinase, anticholinesterase and cytotoxic activities) was performed on the prepared extracts and the isolated secondary metabolites. The results showed that the EtOAc extract of the trunk bark displayed the highest anti-tyrosinase effect with a percent inhibition of 55.0 ± 1.8% at a concentration of 100 µg/mL. The highest anticholinesterase activity was presented by the same extract with an IC₅₀ value of 99.97 ± 3.01 µg/mL. The EtOAc extract of flowers and that of the trunk bark displayed the best cytotoxic property with IC₅₀ values of 96.00 ± 2.85 and 88.75 ± 2.00 µg/mL, respectively, against the human cervical cancer cell line (HeLa), and IC₅₀ values of 188.23 ± 3.88 and 197.00 ± 4.25 µg/mL, respectively, against the human lung cancer (A549) cell lines. Biological investigation of the pure compounds showed that the two 8,3'-neolignan glycosides, plucheosides D₁-D₂, generate the highest anti-tyrosinase potency with a percent inhibition of 61.4 ± 2.0 and 79.5 ± 2.3%, respectively, at a concentration of 100 µM. The iridoid glycosides exhibited a significant anticholinesterase activity with IC₅₀ values ranging from 17.19 ± 1.02 to 52.24 ± 2.50 µM. Triterpene pentacyclic acids and iridoid glycosides exerted encouraging cytotoxic effects against HeLa with IC₅₀ values ranging from 9.00 ± 1.10 to 25.00 ± 1.00 µM. The study of the structure-activity relationship (SAR) has been sufficiently and widely discussed. The natural compounds that exhibited the significant bioactivities were docked.

Keywords: Anti-tyrosinase; Anticholinesterase; Citharexylum spinosum L.; Cytotoxic; Molecular docking; SAR analysis; Verbenaceae.