Title:Synthesis and in vitro Evaluation of the Anticancer Potential of New Aminoalkanol Derivatives of Xanthone
VOLUME: 16 ISSUE: 12
Author(s):Natalia Szkaradek, Daniel Sypniewski, Anna M. Waszkielewicz, Agnieszka Gunia-Krzyżak, Anna Galilejczyk, Sabina Gałka, Henryk Marona and Ilona Bednarek
Affiliation:Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
Keywords:Xanthones, xanthone derivatives, cancer, cell proliferation, cell migration, metastasis.
Abstract:A series of 15 derivatives of xanthone were synthesized and evaluated for the
anticancer activity. The structure of the tested compounds was diversified to establish structureactivity
relationships. The following evaluations were carried out: cytotoxicity-proliferation
tests, apoptosis detection, expression of apoptosis and proliferation-related genes, expression
and activity of gelatinases A and B, wound migration assays, and cell adhesion to MatrigelTMcoated
plates.
Four compounds (7, 12, 13 and 15) displayed direct cytotoxicity at micromolar concentrations
toward the studied cell lines. They also significantly affected the expression of proliferationapoptosis
markers, and 13 demonstrated as strong influence as α-mangostin, that served as a
natural standard in our study. These four compounds also decreased the expression and activity
of gelatinases, and inhibited the migration-motility potential of cancer cells. The influence of
compounds 7 and 12 on MMPs mRNA levels even exceeded the activity of α-mangostin and
shRNA-mediated silencing; zymography revealed that 7, 13 and 15 were as equally active as α-mangostin, despite
their higher IC50 values. The highest activity to inhibit motility and migration of cancer cells was demonstrated by 7,
12, 15, and by α-mangostin; and this was almost equal to shRNA-mediated silencing. Structural features predetermining
compound activity were: substitution at position C4 instead of C2, and presence of a chlorine atom and allyl moiety.
These results indicate that synthesis of aminoalkanol derivatives of xanthone may lead to successful establishment of
new potential anticancer chemicals.
