title: Synthesis, in vitro and computational studies of 1,4-disubstituted 1,2,3-triazoles as potential α-glucosidase inhibitors.
abstract: 1,4-Disubstituted-1,2,3-triazoles were synthesized by Cu(I) catalyzed click reaction, where the azides, with electron donating and electron withdrawing groups acted as 1,3-dipoles and 1-ethynyl-1-cyclohexanol served as the terminal alkyne. These synthesized triazoles were subjected to enzymatic assay which showed promising activity against α-glucosidase; 1-(2-cyano-4-nitrophenyl)-4-(1-hydroxycyclohexyl)-1H-1,2,3-triazole 3m being the most active members of the library. Molecular docking studies of these triazoles with the homology-modeled α-glucosidase protein were also performed to delineate ligand-protein interactions at molecular level which suggested that Phe157, Arg312 and His279 are the major interacting residues in the biding site of the protein and may have a significant role in the inhibition of enzyme's function.
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Farukh
authors.initials: F
authors.lastname: Jabeen
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Syeda Aaliya
authors.initials: SA
authors.lastname: Shehzadi
authors.affiliation: Department of Bio-sciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 45600, Pakistan.
authors.forename: Muhammad Qaiser
authors.initials: MQ
authors.lastname: Fatmi
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Sobia
authors.initials: S
authors.lastname: Shaheen
authors.affiliation: Pharmaceutical Research Centre, Pakistan Council of Scientific and Industrial Research Laboratories Complex, Karachi 75280, Pakistan.
authors.forename: Lubna
authors.initials: L
authors.lastname: Iqbal
authors.affiliation: Pharmaceutical Research Centre, Pakistan Council of Scientific and Industrial Research Laboratories Complex, Karachi 75280, Pakistan.
authors.forename: Nighat
authors.initials: N
authors.lastname: Afza
authors.affiliation: Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, USA. Electronic address: sspanda12@gmail.com.
authors.forename: Siva S
authors.initials: SS
authors.lastname: Panda
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan; Pakistan Council for Science and Technology, Islamabad 45320, Pakistan. Electronic address: fla_qau@yahoo.com.
authors.forename: Farzana Latif
authors.initials: FL
authors.lastname: Ansari
mesh_terms: D000595:Amino Acid Sequence; D001409:Bacillus cereus / Q000201:enzymology; D001665:Binding Sites; D020134:Catalytic Domain; D057930:Click Chemistry; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D014230:Triazoles; D000520:alpha-Glucosidases
keywords: 1,2,3-Triazoles; Click chemistry; Computational studies; Molecular modeling; α-Glucosidase inhibitors