BackgroundXanthone 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 methodsThe 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 semi-empirical 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.ResultsThe 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.ConclusionThe 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.

Objective: To demonstrate the potential ofdifferent xanthone derivatives as cyclooxygenase-2 (COX-2) inhibitor agents and their selectivity against cycloooxygenase-1 (COX-1) and COX-2 using molecular simulation. Methods:Nine novel xanthone derivatives (compounds A-I) were employed to dock against protein COX-2 (Protein Data Bank/PDB ID: 1CX2) and COX-1 (PDB ID: 3N8Z). Celecoxib, a selective COX-2 inhibitor, was chosen as a control compound. The free binding energy produced by the docking was scored using Protein-Ligand Ant System (PLANTS) and the hydrogen bonds (H-bonds) between ligands and enzymes were visualised using Pymol.Results: Molecular docking studies revealed that celecoxib docked to the active site of COX-2 enzyme, but not to COX-1; where as xanthone derivatives docked to the active site of both COX-2 and COX-1. Free binding energy of xanthone derivatives ranged between-73, 57 to-79,18 and between-73,06 to-79,25 against COX-2 and COX-1, respectively, and-78,13 against celecoxib. H-bonds in the molecule of xanthone derivatives and COX-2 protein were found in amino acid residues Arg 120 , Tyr 355 , Tyr 385 , and Ser 353 . There was an insignificant difference between the free binding energyof xanthone derivatives against COX-2 and against COX-1, suggesting that their inhibition was non-selective. Conclusion:In conclusion, in silico studies showed that xanthone derivatives could be effective as potential inhibitors against COX-2, although they are not selective.

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The study of xanthone derivatives as cytotoxic agents in cancer is increasing. This study was conducted to explore the Quantitative Structure-Activity Relationship (QSAR) of xanthones as cytotoxic agents in HepG2 cells, to find compounds with better potency. The data set were taken from the previous study, involving 26 xanthone derivates and their cytotoxic activities in Inhibitory Concentration 50% (IC50). The parameters (descriptors) were obtained from quantum mechanics calculation using semiempirical AM1 method and QSAR models determined with principle component regression, with log (1/IC50) as a dependent variable and five latent variables as independent variables. From the 26 main descriptors, PCR reduced them to five latent variables (1st– 5th LV). The QSAR analysis gave the best model as follows: log (1/IC50) = 4.592 – 0.204 LV1 + 0.295 LV2 + 0.028 LV3 (n = 26, r = 0.571, SE = 0.234, Fcount/Ftable ratio = 1.165, PRESS value = 3.766). The study concluded that the descriptors contributed to anticancer activity were volume, mass, surface area, log P, dipole moment, HOMO energy, LUMO energy, and atomic net charge of some atoms. Modifications of substitution that would contribute to cytotoxic activity can be performed at phenyl ring A and C, but not at B.

Background: Colorectal cancer is the 3rd most common type of cancer in the world with unsatisfactory therapeutic effectiveness. One of the efforts being made to overcome this problem is by extracting various new chemotherapy agents, including herbal plants. The Nyamplung plant (Calophyllum inophyllum L.) is reported to contain calophyllolide, triterpene, coumarin, saponin, biflavonoids, benzophenones and neoflavanoids which are potential anticancer agents. Objective: This study aims to determine the cytotoxic activity of ethanolic extract of fruit shells and seeds of Nyamplung (Calophyllum inophyllum L.) on WiDr colorectal cancer cells and their selectivity on normal cells (Vero).Methods: The fruit and seeds of Nyamplung were extracted by maceration with 70% ethanol solvent. The cytotoxic test was carried out by the 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) method, with doxorubicin as a positive control. Data analyzed using Microsoft Excel software using linear regression analysis. The IC50 value and selectivity index were used as indicator of toxicity selectivity.Results: The IC50 value of the ethanolic extract of Nyamplung fruit shells on WiDr was 42.47 µg/ml with a selectivity index of 1.50. Meanwhile, the IC50 value of ethanolic extract of Nyamplung seeds was 1,030.41 µg/ml with a selectivity index of 67,982,414.71. Doxorubicin as a positive control obtained IC50 value on WiDr cells of 3.49 µg/ml with a selectivity index of 764.41.Conclusion: The ethanolic extract of Nyamplung seeds was not cytotoxic against WiDr colorectal cancer cells, while the ethanolic extract of Nyamplung fruit sell was moderate cytotoxic with low selectivity index.