Synthesis, biological evaluation and mechanistic studies of totarol amino alcohol derivatives as potential antimalarial agents.
作者： Claire Tacon , Eric M. Guantai , Peter J. Smith , Kelly Chibale
DOI: 10.1016/J.BMC.2011.11.060
关键词:
摘要: Abstract Herein we report on the semisynthesis and biological evaluation of β-amino alcohol derivatives natural product totarol other simple aromatic systems. All exhibited higher antiplasmodial activity than [IC 50 : 11.69 μM (K1, chloroquine multi-drug resistant strain), 11.78 μM (D10, sensitive strain)]— 12e was most active 0.63 μM (K1), 0.61 μM (D10)]. The phenyl naphthyl were much less their corresponding equivalents. majority more against K1 D10 strains Plasmodium falciparum , a trend similar to inverse relationship observed with established aryl-amino antimalarial mefloquine. Selected compounds shown affect erythrocyte morphology, inhibit invasion trigger CQ accumulation.
elsevier.com
sci-hub.se 参考文章(28)
In vitro antiplasmodial activity of abietane and totarane diterpenes isolated from Harpagophytum procumbens (devil's claw). Planta Medica. ,vol. 69, pp. 720- 724 ,(2003) , 10.1055/S-2003-42778
Kelly Chibale, Eric M Guantai, Collen Masimirembwa, Extracting molecular information from African natural products to facilitate unique African-led drug-discovery efforts Future Medicinal Chemistry. ,vol. 3, pp. 257- 261 ,(2011) , 10.4155/FMC.10.299
W Trager, J. Jensen, Human malaria parasites in continuous culture Science. ,vol. 193, pp. 673- 675 ,(1976) , 10.1126/SCIENCE.781840
Keiko Yamaji, Shigeta Mori, Masaru Akiyama, Atsushi Kato, Tadakazu Nakashima, The Antifungal Compound Totarol of Thujopsis dolabrata var. hondai Seeds Selects for Fungi on Seedling Root Surfaces Journal of Chemical Ecology. ,vol. 33, pp. 2254- 2265 ,(2007) , 10.1007/S10886-007-9390-2
A. F. Cowman, D. Galatis, J. K. Thompson, Selection for mefloquine resistance in Plasmodium falciparum is linked to amplification of the pfmdr1 gene and cross-resistance to halofantrine and quinine. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 91, pp. 1143- 1147 ,(1994) , 10.1073/PNAS.91.3.1143
Vipan Kumar, Aman Mahajan, Kelly Chibale, Synthetic medicinal chemistry of selected antimalarial natural products Bioorganic & Medicinal Chemistry. ,vol. 17, pp. 2236- 2275 ,(2009) , 10.1016/J.BMC.2008.10.072
Cailean Clarkson, Chitalu C. Musonda, Kelly Chibale, William E. Campbell, Peter Smith, Synthesis of totarol amino alcohol derivatives and their antiplasmodial activity and cytotoxicity Bioorganic & Medicinal Chemistry. ,vol. 11, pp. 4417- 4422 ,(2003) , 10.1016/S0968-0896(03)00491-7
Chris Lambros, Jerome P. Vanderberg, Synchronization of Plasmodium falciparum erythrocytic stages in culture. Journal of Parasitology. ,vol. 65, pp. 418- 420 ,(1979) , 10.2307/3280287
Travis Harrison, Benjamin U Samuel, Thomas Akompong, Heidi Hamm, Narla Mohandas, Jon W Lomasney, Kasturi Haldar, Erythrocyte G Protein-Coupled Receptor Signaling in Malarial Infection Science. ,vol. 301, pp. 1734- 1736 ,(2003) , 10.1126/SCIENCE.1089324
Eric M. Guantai, Kanyile Ncokazi, Timothy J. Egan, Jiri Gut, Philip J. Rosenthal, Peter J. Smith, Kelly Chibale, Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds Bioorganic & Medicinal Chemistry. ,vol. 18, pp. 8243- 8256 ,(2010) , 10.1016/J.BMC.2010.10.009