{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:03:05Z","timestamp":1787594585552,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T00:00:00Z","timestamp":1657411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Bia\u0142ystok","award":["SUB\/2\/DN\/22\/003\/2212"],"award-info":[{"award-number":["SUB\/2\/DN\/22\/003\/2212"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Four new compounds, 5-hydroxy-2\u2032,6\u2032-dimethoxyflavone (4), 5-hydroxy-2\u2032,3\u2032,6\u2032-trimethoxyflavone (5), 5-dihydroxy-6-methoxyflavone (6), and 5,6\u2032-dihydroxy-2\u2032,3\u2032-dimethoxyflavone (7), and three known compounds, 1,3-diphenylpropane-1,3-dione (1), 5-hydroxyflavone (2), and 5-hydroxy-2\u2032-methoxyflavone (3), were isolated from the aerial parts of Hottonia palustris. Their chemical structures were determined through the use of spectral, spectroscopic and crystallographic methods. The quantitative analysis of the compounds (1\u20137) and the zapotin (ZAP) in methanol (HP1), petroleum (HP6), and two chloroform extracts (HP7 and HP8) were also determined using HPLC-PDA. The biological activity of these compounds and extracts on the oral squamous carcinoma cell (SCC-25) line was investigated by considering their cytotoxic effects using the MTT assay. Subsequently, the most active compounds and extracts were assessed for their effect on DNA biosynthesis. It was found that all tested samples during 48 h treatment of SCC-25 cells induced the DNA biosynthesis-inhibitory activity: compound 1 (IC50, 29.10 \u00b1 1.45 \u00b5M), compound 7 (IC50, 40.60 \u00b1 1.65 \u00b5M) and extracts ZAP (IC50, 20.33 \u00b1 1.01 \u00b5M), HP6 (IC50, 14.90 \u00b1 0.74 \u00b5g), HP7 (IC50, 16.70 \u00b1 0.83 \u00b5g), and HP1 (IC50, 30.30 \u00b1 1.15 \u00b5g). The data suggest that the novel polymethoxyflavones isolated from Hottonia palustris evoke potent DNA biosynthesis inhibitory activity that may be considered in further studies on experimental pharmacotherapy of oral squamous cell carcinoma.<\/jats:p>","DOI":"10.3390\/molecules27144415","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:06:21Z","timestamp":1657497981000},"page":"4415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["New Polymethoxyflavones from Hottonia palustris Evoke DNA Biosynthesis-Inhibitory Activity in An Oral Squamous Carcinoma (SCC-25) Cell Line"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7133-1817","authenticated-orcid":false,"given":"Jakub W.","family":"Strawa","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bia\u0142ystok, ul. Mickiewicza 2A, 15-230 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7702-6493","authenticated-orcid":false,"given":"Katarzyna","family":"Jakimiuk","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bia\u0142ystok, ul. Mickiewicza 2A, 15-230 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"Szoka","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Euroregional Center of Pharmacy, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bia\u0142ystok, ul. Mickiewicza 2D, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9339-7745","authenticated-orcid":false,"given":"Krzysztof","family":"Brzezinski","sequence":"additional","affiliation":[{"name":"Department of Structural Biology of Prokaryotic Organisms, Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12\/14, 61-074 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Drozdzal","sequence":"additional","affiliation":[{"name":"Department of Structural Biology of Prokaryotic Organisms, Institute of Bioorganic Chemistry, Polish Academy of Sciences, ul. Noskowskiego 12\/14, 61-074 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8476-2023","authenticated-orcid":false,"given":"Jerzy A.","family":"Pa\u0142ka","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Euroregional Center of Pharmacy, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bia\u0142ystok, ul. Mickiewicza 2D, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4063-1048","authenticated-orcid":false,"given":"Micha\u0142","family":"Tomczyk","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bia\u0142ystok, ul. Mickiewicza 2A, 15-230 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA. Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"799","DOI":"10.3389\/fpls.2015.00799","article-title":"Plant derived substances with anti-cancer activity: From folklore to practice","volume":"6","author":"Fridlender","year":"2015","journal-title":"Front. Plant. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Seca, A., and Pinto, D. (2018). Plant secondary metabolites as anticancer agents: Successes in clinical trials and therapeutic application. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010263"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Forni, C., Rossi, M., Borromeo, I., Feriotto, G., Platamone, G., Tabolacci, C., Mischiati, C., and Beninati, S. (2021). Flavonoids: A myth or a reality for cancer therapy?. Molecules, 26.","DOI":"10.3390\/molecules26123583"},{"key":"ref_5","first-page":"100010","article-title":"Therapeutic role of flavonoids and flavones in cancer prevention: Current trends and future perspectives","volume":"3","author":"Khan","year":"2021","journal-title":"Eur. J. Med. Chem. Reports"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1016\/j.biocel.2013.10.004","article-title":"Flavonoids as prospective compounds for anti-cancer therapy","volume":"45","author":"Ravishankar","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/cbin.11266","article-title":"Effects of flavonoids on tongue squamous cell carcinoma","volume":"44","author":"Bonneau","year":"2020","journal-title":"Cell Biol. Int."},{"key":"ref_8","unstructured":"Stanis\u0142aw, K., and Grzegorz, K. (2015). Flora Polski. Ro\u015bliny wodne i bagienne, MULTICO Oficyna Wydawnicza."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"W\u0142odarczyk, M., Pasikowski, P., Osiewa\u0142a, K., Frankiewicz, A., Dry\u015b, A., and Gle\u0144sk, M. (2020). In search of high-yielding and single-compound-yielding plants: New sources of pharmaceutically important saponins from the Primulaceae family. Biomolecules, 10.","DOI":"10.3390\/biom10030376"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ramesh, S., Rajan, R., and Santhanam, R. (2013). Freshwater Phytopharmaceutical Compounds, CRC Press.","DOI":"10.1201\/b15407"},{"key":"ref_11","unstructured":"(2022, May 17). Bach Original Flower Remedies. Available online: https:\/\/www.bachremedies.com\/en-us\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1080\/14756366.2021.2014832","article-title":"Flavonoids as tyrosinase inhibitors in in silico and in vitro models: Basic framework of SAR using a statistical modelling approach","volume":"37","author":"Jakimiuk","year":"2022","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_13","first-page":"1544","article-title":"Preliminary studies of the chemical composition and cytotoxic activity of Hottonia palustris herb","volume":"85","author":"Strawa","year":"2019","journal-title":"Planta Med."},{"key":"ref_14","first-page":"1304","article-title":"Cytotoxic effect on human melanoma cell lines and tyrosinase inhibition of Hottonia palustris","volume":"87","author":"Strawa","year":"2021","journal-title":"Planta Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/mrc.4001","article-title":"Correlation of substituted aromatic \u03b2-diketones\u2019 characteristic protons chemical shifts with Hammett substituent constants","volume":"51","author":"Zawadiak","year":"2013","journal-title":"Magn. Reson. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1107\/S2052520620012196","article-title":"A new look at two polymorphic crystal structures of dibenzoylmethane: Relationship between the crystal packing and the hydrogen atom position revealed by quantum chemistry and quantum crystallography methods","volume":"B76","author":"Wojtulewski","year":"2020","journal-title":"Acta Crystallogr. Sect. B Struct. Sci. Cryst. Eng. Mater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1021\/bk-1994-0547.ch031","article-title":"Antitumor-promoting and anti-inflammatory activities of licorice principles and their modified compounds","volume":"Volume 547","author":"Shibata","year":"1994","journal-title":"Food Phytochemicals for Cancer Prevention II"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Peng, Y., Bishop, K.S., and Quek, S.Y. (2019). Compositional analysis and aroma evaluation of Feijoa essential oils from New Zealand grown cultivars. Molecules, 24.","DOI":"10.3390\/molecules24112053"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mabry, T.J., Markham, K.R., and Thomas, M.B. (1970). The systematic identification of flavonoids, Springer.","DOI":"10.1007\/978-3-642-88458-0"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Dias, M.C., Pinto, D.C.G.A., and Silva, A.M.S. (2021). Plant flavonoids: Chemical characteristics and biological activity. Molecules, 26.","DOI":"10.3390\/molecules26175377"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1002\/mrc.2510","article-title":"NMR of a series of novel hydroxyflavothiones","volume":"47","author":"Nguyen","year":"2009","journal-title":"Magn. Reson. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1590\/S0100-40422008000400005","article-title":"New pyranoflavones and trypanocidal activity of compounds isolated from Conchocarpus heterophyllus","volume":"31","author":"Ambrozin","year":"2008","journal-title":"Quim. Nova"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1021\/jf0347160","article-title":"Biological effects of epicuticular flavonoids from Primula denticulata on human leukemia cells","volume":"52","author":"Tokalov","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1007\/BF00567956","article-title":"Flavonoids from Primula turkestanica","volume":"7","author":"Zakharov","year":"1971","journal-title":"Chem. Nat. Compd."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s10600-005-0200-1","article-title":"Flavones from callus tissue of Iris ensata","volume":"41","author":"Boltenkov","year":"2005","journal-title":"Chem. Nat. Compd."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/0031-9422(90)85132-Y","article-title":"5-Hydroxy-6,2\u2032-dimethoxyflavone from Primula denticulata","volume":"29","author":"Wollenweber","year":"1990","journal-title":"Phytochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Somayaji, A., and Shastry, C.S. (2021). Interference of antioxidant flavonoids with MTT tetrazolium assay in a cell free system. J. Pharm. Res. Int., 76\u201383.","DOI":"10.9734\/jpri\/2021\/v33i49A33305"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/ptr.2650090816","article-title":"Catechols and quercetin reduce MTT through iron ions: A possible artefact in cell viability assays","volume":"9","author":"Habtemariam","year":"1995","journal-title":"Phyther. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Strawa, J.W., Jakimiuk, K., and Tomczyk, M. (2021). Zapotin, a polymethoxyflavone, with potential therapeutic attributes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413227"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mohammed, H.A., Abd El-Wahab, M.F., Shaheen, U., Mohammed, A.E.-S.I., Abdalla, A.N., and Ragab, E.A. (2021). Isolation, characterization, complete structural assignment and anticancer activities of the methoxylated flavonoids from Rhamnus disperma roots. Molecules, 26.","DOI":"10.3390\/molecules26195827"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0304-3835(01)00844-8","article-title":"Dibenzoylmethane induces cell cycle deregulation in human prostate cancer cells","volume":"178","author":"Jackson","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kopustinskiene, D.M., Jakstas, V., Savickas, A., and Bernatoniene, J. (2020). Flavonoids as anticancer agents. Nutrients, 12.","DOI":"10.3390\/nu12020457"},{"key":"ref_33","unstructured":"Tutin, T.G., Heywood, V.H., Burges, N.A., Moore, D.M., Valentine, D.H., Walters, S.M., and Webb, D.A. (1972). Flora Europaea, Cambridge University Press."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1107\/S0021889808042726","article-title":"OLEX2: A complete structure solution, refinement and analysis program","volume":"42","author":"Dolomanov","year":"2009","journal-title":"J. Appl. Crystallogr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053273314026370","article-title":"SHELXT-Integrated space-group and crystal-structure determination","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. A Found. Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal structure refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. C Struct. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1107\/S090744490804362X","article-title":"Structure validation in chemical crystallography","volume":"65","author":"Spek","year":"2009","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_38","unstructured":"(2022, May 07). Centre Cambridge Crystallographic Data The Cambridge Crystallographic Data Centre (CCDC). Available online: www.ccdc.cam.ac.uk\/data_request\/cif."},{"key":"ref_39","unstructured":"(2022, May 07). ICH Harmonised Tripartte Guideline Q2(R1) Validation of Analytical Procedures: Text and Methodology. Available online: https:\/\/database.ich.org\/sites\/default\/files\/Q2%28R1%29Guideline.pdf."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11085","DOI":"10.1111\/jcmm.17031","article-title":"Santin and cirsimaritin from Betula pubescens and Betula pendula buds induce apoptosis in human digestive system cancer cells","volume":"25","author":"Szoka","year":"2021","journal-title":"J. Cell. Mol. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/14\/4415\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:47:30Z","timestamp":1760140050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/14\/4415"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,10]]},"references-count":40,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["molecules27144415"],"URL":"https:\/\/doi.org\/10.3390\/molecules27144415","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,10]]}}}