| Title |
Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs
|
|---|---|
| Published in |
Drug Design, Development and Therapy, January 2018
|
| DOI | 10.2147/dddt.s149973 |
| Pubmed ID | |
| Authors |
Isnatin Miladiyah, Jumina Jumina, Sofia Mubarika Haryana, Mustofa Mustofa |
| Abstract |
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. 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 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. 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. 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. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 25% |
| Unknown | 3 | 75% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Practitioners (doctors, other healthcare professionals) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 80 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 80 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 11 | 14% |
| Student > Master | 10 | 13% |
| Other | 4 | 5% |
| Researcher | 4 | 5% |
| Lecturer | 4 | 5% |
| Other | 13 | 16% |
| Unknown | 34 | 43% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 10 | 13% |
| Biochemistry, Genetics and Molecular Biology | 9 | 11% |
| Medicine and Dentistry | 8 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 9% |
| Agricultural and Biological Sciences | 3 | 4% |
| Other | 5 | 6% |
| Unknown | 38 | 48% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 February 2018.
All research outputs
#15,879,822
of 25,584,565 outputs
Outputs from Drug Design, Development and Therapy
#876
of 2,254 outputs
Outputs of similar age
#249,018
of 450,901 outputs
Outputs of similar age from Drug Design, Development and Therapy
#18
of 38 outputs
Altmetric has tracked 25,584,565 research outputs across all sources so far. This one is in the 36th percentile – i.e., 36% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,254 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one has gotten more attention than average, scoring higher than 59% of its peers.
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We're also able to compare this research output to 38 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.