title: Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions.
abstract: 2-Indolcarbohydrazones 1-28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3±0.11-226.4±6.8μM was observed while comparing these outcomes with the standard acarbose (IC50=906.0±6.3μM). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of νCO, νNC and νCH (CH in NCH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds.
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia. Electronic address: taha_hej@yahoo.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Taha
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Nor Hadiani
authors.initials: NH
authors.lastname: Ismail
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Kulsoom
authors.initials: K
authors.lastname: Javaid
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
authors.forename: Syahrul
authors.initials: S
authors.lastname: Imran
authors.affiliation: Chemistry Department, College of Sciences and Humanities, Sattam bin Abdulaziz University, P.O. Box 83, Al-Kharj 11942, Saudi Arabia.
authors.forename: El Hassane
authors.initials: el H
authors.lastname: Anouar
authors.affiliation: Department of Biohemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Wadood
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.lastname: Atia-Tul-Wahab
authors.affiliation: Center for Advanced Drug Research, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Syed Muhammad
authors.initials: SM
authors.lastname: Saad
authors.affiliation: Department of Chemistry, Hazara University, Mansehra 21120, Khyber Pukhtunkhwa, Pakistan.
authors.forename: Fazal
authors.initials: F
authors.lastname: Rahim
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21412, Saudi Arabia.
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D004305:Dose-Response Relationship, Drug; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011789:Quantum Theory; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: C000610426:2-indolcarbohydrazone; D065089:Glycoside Hydrolase Inhibitors; D006835:Hydrazones; D007211:Indoles; D000520:alpha-Glucosidases
keywords: 2-Indolcarbohydrazones; Density Functional Theory (DFT); In silico studies; Structure–activity relationship; α-Glucosidase inhibition