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Bioorg Chem. 2015 Dec;63:24-35. doi: 10.1016/j.bioorg.2015.09.001. Epub 2015 Sep 10.

Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions.

Author information

1
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.
2
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.
3
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
4
Chemistry Department, College of Sciences and Humanities, Sattam bin Abdulaziz University, P.O. Box 83, Al-Kharj 11942, Saudi Arabia.
5
Department of Biohemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
6
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
7
Center for Advanced Drug Research, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan.
8
Department of Chemistry, Hazara University, Mansehra 21120, Khyber Pukhtunkhwa, Pakistan.
9
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.

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.

KEYWORDS:

2-Indolcarbohydrazones; Density Functional Theory (DFT); In silico studies; Structure–activity relationship; α-Glucosidase inhibition

PMID:
26398141
DOI:
10.1016/j.bioorg.2015.09.001
[Indexed for MEDLINE]

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