title: Pyridine sulfonamide as a small key organic molecule for the potential treatment of type-II diabetes mellitus and Alzheimer's disease: In vitro studies against yeast α-glucosidase, acetylcholinesterase and butyrylcholinesterase.
abstract: This paper presents the efficient high yield synthesis of novel pyridine 2,4,6-tricarbohydrazide derivatives (4a-4i) along with their α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities. The enzymes inhibition results showed the potential of synthesized compounds in controlling both type-II diabetes mellitus and Alzheimer's disease. In vitro biological investigations revealed that most of compounds were more active against yeast α-glucosidase than the reference compound acarbose (IC50 38.25±0.12μM). Among the tested series the compound 4c bearing 4-flouro benzyl group was noted to be the most active (IC50 25.6±0.2μM) against α-glucosidase, and it displayed weak inhibition activities against AChE and BChE. Compound 4a exhibited the most desired results against all three enzymes, as it was significantly active against all the three enzymes; α-glucosidase (IC50 32.2±0.3μM), AChE (IC50 50.2±0.8μM) and BChE (IC50 43.8±0.8μM). Due to the most favorable activity of 4a against the tested enzymes, for molecular modeling studies this compound was selected to investigate its pattern of interaction with α-glucosidase and AChE targets.
authors.affiliation: Department of Chemistry, GC University, Lahore 54000, Pakistan.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Riaz
authors.affiliation: Department of Chemistry, GC University, Lahore 54000, Pakistan. Electronic address: iuklodhi@yahoo.com.
authors.forename: Islam Ullah
authors.initials: IU
authors.lastname: Khan
authors.affiliation: Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.affiliation: Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.lastname: Qurat-Ul-Ain
authors.affiliation: Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Shaukat
authors.affiliation: Department of Chemistry, GC University, Lahore 54000, Pakistan.
authors.forename: Tanzeel Ur
authors.initials: TU
authors.lastname: Rehman
authors.affiliation: Department of Chemistry, GC University, Lahore 54000, Pakistan.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Mutahir
authors.affiliation: Department of Chemistry, GC University, Lahore 54000, Pakistan.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Department of Chemistry, GC University, Lahore 54000, Pakistan.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mustafa
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan. Electronic address: drmyar@ciitlahore.edu.pk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yar
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D002800:Cholinesterase Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D011725:Pyridines; D013449:Sulfonamides; C000610428:pyridine sulfonamide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000520:alpha-Glucosidases
keywords: AChE; Alzheimer’s disease; BChE; Diabetes mellitus type-II; Pyridine derivatives; α-glucosidase