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Kelly Chibale - One of the best experts on this subject based on the ideXlab platform.

  • Synthesis, biological evaluation and mechanistic studies of totarol Amino Alcohol derivatives as potential antimalarial agents.
    Bioorganic & medicinal chemistry, 2011
    Co-Authors: Claire Tacon, Eric M. Guantai, Pete Smith, Kelly Chibale
    Abstract:

    Herein we report on the semisynthesis and biological evaluation of β-Amino Alcohol derivatives of the natural product totarol and other simple aromatic systems. All β-Amino Alcohol derivatives of totarol exhibited higher antiplasmodial activity than totarol [IC(50): 11.69 μM (K1, chloroquine and multi-drug resistant strain), and 11.78 μM (D10, chloroquine sensitive strain)]-12e was the most active [IC(50): 0.63 μM (K1), and 0.61 μM (D10)]. The phenyl and naphthyl β-Amino Alcohol derivatives were much less active than their corresponding totarol equivalents. The majority of the β-Amino Alcohol derivatives of totarol were more active against K1 than the D10 strains of Plasmodium falciparum, a trend similar to the inverse relationship observed with the established aryl-Amino Alcohol antimalarial mefloquine. Selected compounds were shown to affect erythrocyte morphology, inhibit erythrocyte invasion and trigger CQ accumulation.

  • comparison of the antiplasmodial and falcipain 2 inhibitory activity of β Amino Alcohol thiolactone chalcone and isatin chalcone hybrids
    Bioorganic & Medicinal Chemistry Letters, 2010
    Co-Authors: Renate H Hans, Kelly Chibale
    Abstract:

    : The synthesis and biological evaluation of two novel series of natural-product-like hybrids based on the chalcone, thiolactone and isatin scaffolds is herein described. Results for a 36-member beta-Amino Alcohol triazole library showed that the thiolactone-chalcones, with IC(50)s ranging from 0.68 to 6.08 microM, were more active against W2 strain Plasmodium falciparum than the isatin-chalcones with IC(50)s of 14.9 microM or less. Also of interest is falcipain-2 inhibitory activity displayed by the latter, whereas the thiolactone-chalcones lacked enzyme inhibitory activity.

  • Comparison of the antiplasmodial and falcipain-2 inhibitory activity of β-Amino Alcohol thiolactone-chalcone and isatin-chalcone hybrids.
    Bioorganic & medicinal chemistry letters, 2010
    Co-Authors: Renate H Hans, Jiri Gut, Philip J. Rosenthal, Kelly Chibale
    Abstract:

    Abstract The synthesis and biological evaluation of two novel series of natural-product-like hybrids based on the chalcone, thiolactone and isatin scaffolds is herein described. Results for a 36-member β-Amino Alcohol triazole library showed that the thiolactone-chalcones, with IC 50 s ranging from 0.68 to 6.08 μM, were more active against W2 strain Plasmodium falciparum than the isatin-chalcones with IC 50 s of 14.9 μM or less. Also of interest is falcipain-2 inhibitory activity displayed by the latter, whereas the thiolactone-chalcones lacked enzyme inhibitory activity.

Akkattu T. Biju - One of the best experts on this subject based on the ideXlab platform.

M Muthukrishnan - One of the best experts on this subject based on the ideXlab platform.

Daniel G Anderson - One of the best experts on this subject based on the ideXlab platform.

  • bioinspired alkenyl Amino Alcohol ionizable lipid materials for highly potent in vivo mrna delivery
    Advanced Materials, 2016
    Co-Authors: Owen S Fenton, Robert Langer, Kevin J Kauffman, Rebecca L Mcclellan, Eric A Appel, Robert J Dorkin, Mark W Tibbitt, Michael W Heartlein, Frank Derosa, Daniel G Anderson
    Abstract:

    Thousands of human diseases could be treated by selectively controlling the expression of specific proteins in vivo. A new series of alkenyl Amino Alcohol (AAA) ionizable lipid nanoparticles (LNPs) capable of delivering human mRNA with unprecedented levels of in vivo efficacy is demonstrated. This study highlights the importance of utilizing synthesis tools in tandem with biological inspiration to understand and improve nucleic acid delivery in vivo.

Renate H Hans - One of the best experts on this subject based on the ideXlab platform.