1,2,3-Triazole-nimesulide hybrid: Their design, synthesis and evaluation as potential anticancer agents
- Bioorg Med Chem Lett. 2017 Feb 1;27(3):518-523. doi: 10.1016/j.bmcl.2016.12.030.
- 1. Department of Chemistry, MNR Degree & PG College, Kukatpally, Hyderabad 500085, India; Centre for Chemical Sciences and Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, India.
- 2. Centre for Chemical Sciences and Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, India.
- 3. Chemical Biology Laboratory, Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
- 4. Doctoral Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, Institute for Interdisciplinary Research, University of Coimbra (IIIUC), 3004-517 Coimbra, Portugal.
- 5. Department of Chemistry, MNR Degree & PG College, Kukatpally, Hyderabad 500085, India. Electronic address: [email protected].
A new hybrid template has been designed by integrating the structural features of nimesulide and the 1,2,3-triazole moiety in a single molecular entity at the same time eliminating the problematic nitro group of nimesulide. The template has been used for the generation of a library of molecules as potential Anticancer agents. A mild and greener CuAAC approach has been used to synthesize these compounds via the reaction of 4-azido derivative of nimesulide and terminal alkynes in water. Three of these compounds showed promising growth inhibition (IC50 ∼6-10μM) of A549, HepG2, HeLa and DU145 Cancer cell lines but no significant effects on HEK293 cell line. They also inhibited PDE4B in vitro (60-70% at 10μM) that was supported by the docking studies (PLP score 87-94) in silico.