A high-throughput (HT) paradigm generating LC-MS-UV-ELSD-based natural product libraries to discover compounds with new bioactivities and or molecular structures is presented. To validate this methodology, an extract of the Indo-Pacific marine sponge Cacospongia mycofijiensis was evaluated using assays involving cytoskeletal profiling, tumor cell lines, and parasites. Twelve known compounds were identified including latrunculins (1-4, 10), fijianolides (5, 8, 9), mycothiazole (11), aignopsanes (6, 7), and sacrotride A (13). Compounds 1-5 and 8-11 exhibited bioactivity not previously reported against the parasite T. brucei, while 11 showed selectivity for lymphoma (U937) tumor cell lines. Four new compounds were also discovered including aignopsanoic acid B (13), apo-latrunculin T (14), 20-methoxy-fijianolide A (15), and aignopsane ketal (16). Compounds 13 and 16 represent important derivatives of the aignopsane class, 14 exhibited inhibition of T. brucei without disrupting microfilament assembly, and 15 demonstrated modest microtubule-stabilizing effects. The use of removable well plate libraries to avoid false positives from extracts enriched with only one or two major metabolites is also discussed. Overall, these results highlight the advantages of applying modern methods in natural products-based research to accelerate the HT discovery of therapeutic leads and/or new molecular structures using LC-MS-UV-ELSD-based libraries.
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http://dx.doi.org/10.1021/np200673b | DOI Listing |
Eur J Med Chem
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Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China. Electronic address:
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Department of Chemistry, Yazd University, Yazd, 89195-741, Iran.
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View Article and Find Full Text PDFWorld J Microbiol Biotechnol
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School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China.
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School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Nitrogen (N) is one of the three major elements required for plant growth and development. It is of great significance to study the effects of different nitrogen application levels on the growth and root exudates of Phlomoides rotata, and can provide a theoretical basis for its scientific application of fertilizer to increase production. In this study, Phlomoides rotata were grown under different nitrogen conditions for two months.
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