| Autor: |
Kimani NM; Department of Physical Sciences, University of Embu, Embu P.O. Box 6-60100, Kenya., Ochieng CO; Department of Chemistry, Maseno University, Maseno P.O. Box 333-40105, Kenya., Ogutu MD; Department of Chemistry, Maseno University, Maseno P.O. Box 333-40105, Kenya., Yamo KO; Department of Chemistry, Maseno University, Maseno P.O. Box 333-40105, Kenya., Onyango JO; School of Chemical Sciences and Technology, Technical University of Kenya, Nairobi P.O. Box 52428-00200, Kenya., Santos CBR; Graduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá 68903-419, AP, Brazil.; Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, Brazil. |
| Abstrakt: |
Compounds from Zanthoxylum chalybeum Engl. were previously reported for inhibitory activities of amylase and glucosidase enzymatic action on starch as a preliminary study toward the establishment of a management strategy against postprandial hyperglycemia, however, the inhibitory kinetics and molecular interaction of these compounds were never established. A study was thus designed to establish the inhibitory kinetics and in silico molecular interaction of α-glucosidase and α-amylase with Z. chalybeum metabolites based on Lineweaver-Burk/Dixon plot analyses and using Molecular Operating Environment (MOE) software, respectively. Skimmianine ( 5 ), Norchelerythrine ( 6 ), 6-Acetonyldihydrochelerythrine ( 7 ), and 6-Hydroxy-N-methyldecarine ( 8 ) alkaloids showed mixed inhibition against both α-glucosidase and α-amylase with comparable K i to the reference acarbose ( p > 0.05) on amylase but significantly higher activity than acarbose on α-glucosidase. One phenolic 2,3-Epoxy-6,7-methylenedioxyconiferol ( 10 ) showed a competitive mode of inhibition both on amylase and glucosidase which were comparable ( p > 0.05) to the activity of acarbose. The other compounds analyzed and displayed varied modes of inhibition between noncompetitive and uncompetitive with moderate inhibition constants included chaylbemide A ( 1 ), chalybeate B ( 2 ) and chalybemide C ( 3 ), fagaramide ( 4 ), ailanthoidol ( 9 ), and sesame ( 11 ). The important residues of the proteins α-glucosidase and α-amylase were found to have exceptional binding affinities and significant interactions through molecular docking studies. The binding affinities were observed in the range of -9.4 to -13.8 and -8.0 to -12.6 relative to the acarbose affinities at -17.6 and -20.5 kcal/mol on α-amylase and α-glucosidase residue, respectively. H-bonding, π-H, and ionic interactions were noted on variable amino acid residues on both enzymes. The study thus provides the basic information validating the application of extracts of Z. chalybeum in the management of postprandial hyperglycemia. Additionally, the molecular binding mechanism discovered in this study could be useful for optimizing and designing new molecular analogs as pharmacological agents against diabetes. |
