Anti-tumour effects of xanthone derivatives and the possible mechanisms of action

Abstract

To explore the potential anti-tumour activities of xanthone derivatives, 26 hydroxylxanthones and benzoxanthones and their structurally modified analogues were examined for potential cytotoxic activities against eight human cancer cell lines. Most of the xanthone derivatives exhibited a higher degree of cytotoxicity on HepG2 cells than on the other seven cancer cell lines. Compound 24 (1,3,7-Trihydroxy-12H-benzo[b] xanthen-12-one) showed the highest degree of cytotoxicity of the tested compounds against HepG2 cells and demonstrated good tumour specificity by exhibiting a much higher degree of cytotoxicity against HepG2 cells than against normal liver cells (L02). Several valuable structure-activity relationships were derived from the cytotoxicity data. In addition, we found that compound 24 could downregulate the expression of the Mcl-1 protein, induce changes in the mitochondrial membrane potential and induce apoptosis in HepG2 cells via the mitochondrial pathway. Compound 24 was also shown to inhibit topoisomerase (topo) II activity and downregulate the levels of both topo II mRNA and protein in HepG2 cells. The present results suggest that due to its potent cytotoxicity and good tumour selectivity, compound 24 may be exploited as a potential lead compound in the development of a new anti-tumour agent with specific activity against liver cancer.

QSAR and docking studies on xanthone derivatives for anticancer activity targeting DNA topoisomerase IIα

“…Prior studies of xanthone showed its promising role in the development of novel anticancer compounds 6. In the present work, we studied the structure activity relationship of xanthone.…”

“…Initially, a total of 64 compounds with reported anticancer activity against the human cervical cancer cell line (HeLa) were used as a training data set while developing the QSAR model (Tables 1 and S1) 6,9–16. The anticancer activity was in IC 50 form.…”

“…Their derivatives are widely distributed in various plants, and they have a variety of biological properties, such as antioxidant, hepato-protective, anti-inflammatory, anti-α-glucosidase, and anticancer properties 6. Due to their antitumor effect, xanthones are attracting more interest.…”

Arylxanthones and arylacridones: a synthetic overview

“…Nevertheless the most recent publications indicate that these tetracyclic ring systems can be potential lead compounds in the development of new antitumour agents [25,26]. To the best of our knowledge arylbenzoxanthones are not found in natural sources and their synthesis is restricted [27,28].…”

Design and docking of novel series of hybrid xanthones as anti-cancer agent to target human DNA topoisomerase 2-alpha

“…Trihydroxyl xanthone and tetrahydroxyl xanthone were exhibited the highest cytotoxic activities during cell line studies. But it was found that the activity of these xanthones does not increase linearly with the increasing number of hydroxyl groups, suggesting that the position and substitutions on hydroxyl group also has an obvious effect on the inhibitory activities of the compounds (Su et al, 2011). The alkoxy derivatives of xanthones revealed that they also possess tremendous power against cancer.…”