alexa Abstract | Design and synthesis of new (secinh3) derivatives as potential cytohesin inhibitors

Indian Journal of Pharmaceutical Sciences
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Research Paper Open Access

Abstract

Cytohesins are small guanine nucleotide exchange factors that stimulate ADP ribosylation factors, Ras-like GTPases, which control various cellular regulatory networks ranging from vesicle trafficking to integrin activation. A small molecule SecinH3 (1,2,4-triazole derivative) in an aptamer displacement assay as a pan-cytohesin Sec7-domain inhibitor was previously identified. Here a series of different SecinH3-analogues was designed and synthesised as potential cytohesin Sec7-domain inhibitors. All final synthesized compounds 6-8, 43-58 and their intermediates were confirmed by 1 H NMR, 13 C NMR and high resolution Mass. Preliminary biological screening of target compounds indictaed that some of the new synthesized secinH3 derivatives showed higher potency and promising activity more than secinH3 itself (unpublished results). Compund 9 and 10 were approximate equal to secinH3 activity as cytohesin antagonist activity. Furthermore compound 52 showed twice inhibition potency if compared to secinH3

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Author(s): Alaa M Hayallah

Keywords

SecinH3, synthesis, 1,2,4-triazole, pipronyloyl moiety, cytohesin inhibitors

 
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