Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs
Isnatin Miladiyah,1,2 Jumina Jumina,3 Sofia Mubarika Haryana,4 Mustofa Mustofa5 1Pharmacology Department, Faculty of Medicine, Islamic University of Indonesia, 2Doctorate Program of Medical Science and Health, Faculty of Medicine, 3Chemistry Department, Faculty of Mathematics and Natural Sciences,...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-01-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/biological-activity-quantitative-structure-activity-relationship-analy-peer-reviewed-article-DDDT |
| _version_ | 1811343130270629888 |
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| author | Miladiyah I Jumina J Haryana SM Mustofa M |
| author_facet | Miladiyah I Jumina J Haryana SM Mustofa M |
| author_sort | Miladiyah I |
| collection | DOAJ |
| description | Isnatin Miladiyah,1,2 Jumina Jumina,3 Sofia Mubarika Haryana,4 Mustofa Mustofa5 1Pharmacology Department, Faculty of Medicine, Islamic University of Indonesia, 2Doctorate Program of Medical Science and Health, Faculty of Medicine, 3Chemistry Department, Faculty of Mathematics and Natural Sciences, 4Histology and Cell Biology Department, Faculty of Medicine, 5Pharmacology and Therapeutic Department, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia 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 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. 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. Keywords: xanthones, anticancer, semiempirical AM1, BuildQSAR, molecular docking |
| first_indexed | 2024-04-13T19:23:23Z |
| format | Article |
| id | doaj.art-3bd0891b5d484bd5aec38c59775858dc |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-04-13T19:23:23Z |
| publishDate | 2018-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-3bd0891b5d484bd5aec38c59775858dc2022-12-22T02:33:26ZengDove Medical PressDrug Design, Development and Therapy1177-88812018-01-01Volume 1214915836381Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugsMiladiyah IJumina JHaryana SMMustofa MIsnatin Miladiyah,1,2 Jumina Jumina,3 Sofia Mubarika Haryana,4 Mustofa Mustofa5 1Pharmacology Department, Faculty of Medicine, Islamic University of Indonesia, 2Doctorate Program of Medical Science and Health, Faculty of Medicine, 3Chemistry Department, Faculty of Mathematics and Natural Sciences, 4Histology and Cell Biology Department, Faculty of Medicine, 5Pharmacology and Therapeutic Department, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia 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 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. 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. Keywords: xanthones, anticancer, semiempirical AM1, BuildQSAR, molecular dockinghttps://www.dovepress.com/biological-activity-quantitative-structure-activity-relationship-analy-peer-reviewed-article-DDDTXanthonesAnticancerSemi-empirical AM1BuildQSARMolecular docking |
| spellingShingle | Miladiyah I Jumina J Haryana SM Mustofa M Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs Drug Design, Development and Therapy Xanthones Anticancer Semi-empirical AM1 BuildQSAR Molecular docking |
| title | Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs |
| title_full | Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs |
| title_fullStr | Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs |
| title_full_unstemmed | Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs |
| title_short | Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs |
| title_sort | biological activity quantitative structure ndash activity relationship analysis and molecular docking of xanthone derivatives as anticancer drugs |
| topic | Xanthones Anticancer Semi-empirical AM1 BuildQSAR Molecular docking |
| url | https://www.dovepress.com/biological-activity-quantitative-structure-activity-relationship-analy-peer-reviewed-article-DDDT |
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