title: 1,2,3-Triazole-nimesulide hybrid: Their design, synthesis and evaluation as potential anticancer agents.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Mareddy
authors.affiliation: Centre for Chemical Sciences and Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, India.
authors.forename: N
authors.initials: N
authors.lastname: Suresh
authors.affiliation: Chemical Biology Laboratory, Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: C Ganesh
authors.initials: CG
authors.lastname: Kumar
authors.affiliation: 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.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Kapavarapu
authors.affiliation: Centre for Chemical Sciences and Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, India.
authors.forename: A
authors.initials: A
authors.lastname: Jayasree
authors.affiliation: Department of Chemistry, MNR Degree & PG College, Kukatpally, Hyderabad 500085, India. Electronic address: sarbani277@yahoo.com.
authors.forename: Sarbani
authors.initials: S
authors.lastname: Pal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D058988:Phosphodiesterase 4 Inhibitors; D014230:Triazoles; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517360:PDE4B protein, human
keywords: 1,2,3-Triazole; Alkyne; Anticancer activity; Azide; Nimesulide