Efficient synthesis and biological evaluation of epiceanothic acid and related compounds |
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Authors: | Zhang Pu Xu Li Qian Keduo Liu Jun Zhang Luyong Lee Kuo-Hsiung Sun Hongbin |
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Affiliation: | a Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China b Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA c Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China d Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan |
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Abstract: | Epiceanothic acid (1) is a naturally occurring, but very rare pentacyclic triterpene with a unique pentacyclic triterpene (PT) structure. An efficient synthesis of 1 starting from betulin (3) has been accomplished in 12-steps with a total yield of 10% in our study. Compound 1 and selected synthetic intermediates were further evaluated as anti-HIV-1 agents, inhibitors of glycogen phosphorylase (GP), and cytotoxic agents. Compound 1 exhibited moderate HIV-1 inhibition. Most importantly, compound 5, with an opened A-ring, showed significant GP inhibitory activity with an IC50 of 0.21 μM, suggesting a potential for development as an anti-diabetic agent. On the other hand, compound 12, with a closed A-ring, showed potent cytotoxicity against A549 and MCF-7 human tumor cell lines, with IC50 values of 0.89 and 0.33 μM, respectively. These results suggest that the A-ring of PTs is an important pharmacophore that could be modified to involve different biological activities. |
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Keywords: | Epiceanothic acid Pentacyclic triterpene Anti-HIV agents Glycogen phosphorylase inhibitors Cytotoxic agents |
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