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• W2015964802 abstract "Anticancer efficacy and absorption, distribution, metabolism, and toxicity studies of Aspergiolide A in early drug development Yuanyuan Wang, Xin Qi, Dehai Li, Tianjiao Zhu, Xiaomei Mo, Jing LiKey Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, People&#39;s Republic of ChinaAbstract: Since the first anthracycline was discovered, many other related compounds have been studied in order to overcome its defects and improve efficacy. In the present paper, we investigated the anticancer effects of a new anthracycline, aspergiolide A (ASP-A), from a marine-derived fungus in vitro and in vivo, and we evaluated the absorption, distribution, metabolism, and toxicity drug properties in early drug development. We found that ASP-A had activity against topoisomerase II that was comparable to adriamycin. ASP-A decreased the growth of various human cancer cells in vitro and induced apoptosis in BEL-7402 cells via a caspase-dependent pathway. The anticancer efficacy of ASP-A on the growth of hepatocellular carcinoma xenografts was further assessed in vivo. Results showed that, compared with the vehicle group, ASP-A exhibited significant anticancer activity with less loss of body weight. A pharmacokinetics and tissue distribution study revealed that ASP-A was rapidly cleared in a first order reaction kinetics manner, and was enriched in cancer tissue. The maximal tolerable dose (MTD) of ASP-A was more than 400 mg/kg, and ASP-A was not considered to be potentially genotoxic or cardiotoxic, as no significant increase of micronucleus rates or inhibition of the hERG channel was seen. Finally, an uptake and transport assay of ASP-A was performed in monolayers of Caco-2 cells, and ASP-A was shown to be absorbed through the active transport pathway. Altogether, these results indicate that ASP-A has anticancer activity targeting topoisomerase II, with a similar structure and mechanism to adriamycin, but with much lower toxicity. Nonetheless, further molecular structure optimization is necessary.Keywords: aspergiolide A, anticancer, anthracyclines, ADMT, drug activity" @default.
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• W2015964802 date "2014-10-01" @default.
• W2015964802 modified "2023-09-25" @default.
• W2015964802 title "Anticancer efficacy and absorption, distribution, metabolism, and toxicity studies of Aspergiolide A in early drug development" @default.
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• W2015964802 doi "https://doi.org/10.2147/dddt.s64989" @default.
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