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The characteristic chemical structures and strong biological activities of this class of compounds attracted attention worldwide. Currently, more than ninety natural podophyllotoxins were isolated, and structure modifications of these molecules were performed to afford a variety of derivatives, which offered optimized anti-tumor activity. This review summarized up to date reports on natural occurring podophyllotoxins and their sources, structural modification and biological activities. Special attention was paid to both structural modification and optimized antitumor activity. It was noteworthy that etoposide, a derivative of podophyllotoxin, could prevent cytokine storm caused by the recent SARS-CoV-2 viral infection.<\/jats:p>","DOI":"10.3390\/molecules28010302","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T03:00:59Z","timestamp":1672628459000},"page":"302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Chemistry and Biological Activities of Naturally Occurring and Structurally Modified Podophyllotoxins"],"prefix":"10.3390","volume":"28","author":[{"given":"Lu","family":"Jin","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, Guangxi Botanical Garden of Medicinal Plants, Nanning 530023, China"},{"name":"Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, College of Pharmacy, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Song","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, Guangxi Botanical Garden of Medicinal Plants, Nanning 530023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Cai","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, College of Pharmacy, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6361-9287","authenticated-orcid":false,"given":"Lijun","family":"Ruan","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, Guangxi Botanical Garden of Medicinal Plants, Nanning 530023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0730-9866","authenticated-orcid":false,"given":"Renwang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, College of Pharmacy, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shah, Z., Gohar, U.F., Jamshed, I., Mushtaq, A., Mukhtar, H., Zia-Ui-Haq, M., Toma, S.I., Manea, R., Moga, M., and Popovici, B. 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