The discovery of a more cytotoxic macrosphelide derivative, including its total synthesis and bioassay are described. Application of the Koide protocol to a readily available propagylic alcohol allowed the rapid and practical synthesis of a macrosphelide A skeleton. This strategy enabled the successful improvement of the cytotoxic activity of the macrosphelide derivative.
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http://dx.doi.org/10.3390/molecules191015572 | DOI Listing |
Molecules
March 2015
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju daero, Jinju, Gyeongnam 660-701, Korea.
Synthetic approaches to macrosphelide derivatives, based on medicinal chemistry, are summarized. This review contains conventional medicinal chemistry approaches, combinatorial chemistry, fluorous tagging techniques and affinity chromatography preparation. In addition, advances in their apoptosis-inducing activities are also included.
View Article and Find Full Text PDFMolecules
September 2014
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju daero, Jinju 660-701, Gyeongnam, Korea.
The discovery of a more cytotoxic macrosphelide derivative, including its total synthesis and bioassay are described. Application of the Koide protocol to a readily available propagylic alcohol allowed the rapid and practical synthesis of a macrosphelide A skeleton. This strategy enabled the successful improvement of the cytotoxic activity of the macrosphelide derivative.
View Article and Find Full Text PDFChemistry
June 2009
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Various artificial macrosphelides were designed and synthesized, including ring-enlarged analogues and epothilone-hybrid compounds. Syntheses were accomplished in an efficient manner by using a ring-closing metathesis (RCM) strategy in a key macrocyclization step. Biological evaluation of these new macrosphelide-based derivatives revealed that several epothilone hybrids, in which a thiazole-containing side chain was incorporated, exhibited potent apoptosis-inducing activity toward human lymphoma cells.
View Article and Find Full Text PDFChem Biol Interact
February 2009
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
The apoptosis-inducing ability of hybrid compounds composed of macrosphelide and thiazole-containing side chain of epothilones was investigated. Among the tested series of hybrid compounds the one containing thiazole side chain at C15 (MSt-2) showed the maximum potency to induce apoptosis, while another containing thiazole side chain at C3 (MSt-6) was less potent. MSt-2 was found to induce apoptosis in human lymphoma (U937) cells in a dose- and time-dependent manner as confirmed by DNA fragmentation analysis.
View Article and Find Full Text PDFAcc Chem Res
February 2008
Kitasato Institute for Life Sciences, Kitasato University and The Kitasato Institute, Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Bioactive natural products produced by microbes have almost limitless potential in pharmaceutical applications, and the organic synthesis of such products as lead compounds will result in the creation of new and widely useful pharmaceutical products. A program of discovery of naturally occurring bioactive microbial metabolites has been ongoing at the Kitasato Institute. We have also developed efficient, rational, and highly flexible production methods for generation of target compounds, synthesis of related compounds, elucidation of their structure-activity relationships, and the possible creation of improved bioactive compounds.
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