Cycloisomerization of acetylenic oximes and hydrazones under gold catalysis: Synthesis and cytotoxic evaluation of isoxazoles and pyrazoles

Journal of Chemical Sciences

Y Arun³  A A M Prince²  Chandrasekar Praveen2¹  P T Perumal³  J C Jeyaveeran² 

[1] Functional Materials Division, Central Electrochemical Research Institute (CSIR laboratory), Karaikudi 630 006, India$$;Department of Chemistry, Ramakrishna Mission Vivekananda College, Mylapore, Chennai 600 004, India$$;Organic Chemistry Division, Central Leather Research Institute (CSIR laboratory), Adyar, Chennai 600 020, India$$

关键词: Gold catalysis;    cycloisomerization;    isoxazoles;    pyrazoles;    cytotoxicity;    molecular docking.;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

The synthesis of substituted isoxazoles and pyrazoles through a general cycloisomerization methodology has been reported. The capability of gold(III) chloride to promote cycloisomerization of both 𝛼, 𝛽-acetylenic oximes and 𝛼, 𝛽-acetylenic hydrazones is the centrepiece of the strategy. A range of acetylenic precursors were investigated to afford 28 examples of the products with good to excellent chemical yields. Selected compounds were screened for their cytotoxic potential towards COLO320 cancer cell lines. The IC50 values of the tested compounds were in the micromolar range, with the best compound, 5-(6-Methoxy-naphthalen-2-yl)-3-phenyl-isoxazole (3h) displaying an IC50 of 38.9 𝜇M. For this compound, the crystal structure in complex with Aurora-A kinase was obtained which revealed details of its binding mode within the active site with a free energy of binding -9.54 kcal/mol.

【 授权许可】

Unknown