| Abstrak/Abstract |
Background: Xanthone derivatives have a wide range of pharmacological activities, such as
those involving antibacterial, antiviral, antimalarial, anthelmintic, anti-inflammatory, antiprotozoal,
and anticancer properties. Among these, we investigated the anticancer properties of
xanthone. This research aimed to analyze the biological activity of ten novel xanthone derivatives,
to investigate the most contributing-descriptors for their cytotoxic activities, and to examine the
possible mechanism of actions of xanthone compound through molecular docking.
Materials and methods: The cytotoxic tests were carried out on WiDR and Vero cell lines,
by a 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay method. The
structural features required for xanthone’s anticancer activity were conducted by using the semiempirical
Austin Model-1 method, and continued with quantitative structure-activity relationship
(QSAR) analysis using BuildQSAR program. The study of the possible mechanism of actions
of the selected xanthone compound was done through molecular docking with PLANTS.
Results: The three novel xanthone derivatives (compounds 5, 7, and 8) exhibited cytotoxic
activity with compound 5 showed the highest degree of cytotoxicity at concentration 9.23 µg/mL
(37.8 µM). The following best equation model was obtained from the BuildQSAR calculation:
log 1/IC50 = ?8.124 qC1 ?35.088 qC2 ?6.008 qC3 + 1.831 u + 0.540 logP ?9.115 (n = 10, r =
0.976, s = 0.144, F = 15.920, Q2 = 0.651, SPRESS = 0.390). This equation model generated
15 proposed new xanthone compounds with better-predicted anticancer activities. A molecular
docking study of compound 5 showed that xanthone formed binding interactions with some
receptors involved in cancer pathology, including telomerase, tumor-promoting inflammation
(COX-2), and cyclin-dependent kinase-2 (CDK2) inhibitor.
Conclusion: The results suggested that compound 5 showed the best cytotoxic activity among
the xanthone derivatives tested. QSAR analysis showed that the descriptors contributed to xanthone’s
cytotoxic activity were the net atomic charge at qC1, qC2, and qC3 positions, also dipole
moment and logP. Compound 5 was suspected to be cytotoxic by its inhibition of telomerase,
COX-2, and CDK2 receptors. |
