Electrochemical Synthesis of New Isoxazoles and Triazoles Tethered with Thiouracil Base as Inhibitors of Histone Deacetylases in Human Breast Cancer Cells.
Divakar Vishwanath, Zhang Xi, Akshay Ravish, Arunkumar Mohan, Shreeja Basappa, Niranjan Pattehalli Krishnamurthy, Santosh L Gaonkar, Vijay Pandey, Peter E Lobie, Basappa Basappa
Author Information
Divakar Vishwanath: Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Mysore 570006, Karnataka, India. ORCID
Zhang Xi: Shenzhen Bay Laboratory, Shenzhen 518055, China. ORCID
Akshay Ravish: Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Mysore 570006, Karnataka, India. ORCID
Arunkumar Mohan: Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Mysore 570006, Karnataka, India. ORCID
Shreeja Basappa: Department of Chemistry, BITS-Pilani Hyderabad Campus, Jawaharnagar 500078, Medchal, Telangana, India.
Niranjan Pattehalli Krishnamurthy: NMR Research Centre, Indian Institute of Science, Bangalore 560012, Karnataka, India.
Santosh L Gaonkar: Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Vijay Pandey: Tsinghua Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China. ORCID
Peter E Lobie: Shenzhen Bay Laboratory, Shenzhen 518055, China.
Basappa Basappa: Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Mysore 570006, Karnataka, India. ORCID
Histone deacetylases (HDACs) are an attractive drug target for the treatment of human breast cancer (BC), and therefore, HDAC inhibitors (HDACis) are being used in preclinical and clinical studies. The need to understand the scope of the mode of action of HDACis, as well as the report of the co-crystal structure of HDAC6/SS-208 at the catalytic site, provoked us to develop an isoxazole-based lead structure called 4-(2-(((1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio) pyrimidin-4-yl) morpholine () and 1-(2-(((3-(p-tolyl) isoxazol-5-yl)methyl)thio) pyrimidin-4-yl) piperidin-4-one () that targets HDACs in human BC cells. We found that the compound or could inhibit the proliferation of BC cells with an IC value of 8.754 and 11.71 µM, respectively. Our detailed analysis showed that compounds could target HDAC in MCF-7 cells. In conclusion, we identified a new structure bearing triazole, isoxazole, and thiouracil moiety, which could target HDAC in MCF-7 cells and serve as a base to make new drugs against cancer.
