Bioactive compounds based on constituents from pericarp of managosteen Barcinia managostana L.

Abstract

Antibacterial activities of α-mangostin (1) and its synthetic derivatives against Staphylococcus aureus and methicillin-resistant S. aureus were conducted and evaluated for the structure-activity relationships (SAR). M3 was as effective as 1 against S. aureus with the MIC value of 0.78 μg/mL, and exhibited twice more bactericidal than 1 with the MBC value of 1.56 μg/mL. The derivatization of hydroxyl groups at C3 and C6 rendered antibacterial activities. In addition, 1 and its synthetic derivatives did not show activity against Candida albicans. In termite antifeedant assay, 1 completely inhibited termite feeding with the %FI of 97.8 and 85.0 at a dose of 100 and 50 µg/disk, respectively. Substitution of hydroxyl groups at C3 and C6 decreased antifeedant activities. SAR studies suggested that the hydroxyl groups at C3 and C6 and the prenyl chains at C2 and C8 may be important for antibacterial and antifeedant activity. The optimal activity was found to depend on a balance of the hydrophilic and hydrophobic portions of molecule. The simplified analogues of gambogic acid (77) and their pharmacological evaluations have been explored. The Pd(0)-catalyzed reverse prenylation of catechols, followed by the Claisen/Diels-Alder reaction cascade provided rapid and efficient access to various caged analogues. SAR studies of these compounds were evaluated in a multi-drug resistant promyelocytic leukemia cell line, HL-60/ADR (Adriamycin). The minimum bioactive motif of such compounds was represented by the intact ABC ring containing the C-ring caged structure. Cluvenone (196) exhibited a comparable cytotoxicity by inducing apoptosis to 77. In addition, 196 was almost 5-fold more toxic to primary B-cell acute lymphoblastic leukemia (IC₅₀ 1.1 μM) than peripheral blood mononuclear cells from normal donors (IC₅₀ 5.2 μM).