Advertisement

Potential antidiabetic activity and molecular docking studies of novel synthesized 3.6-dimethyl-5-oxo-pyrido[3,4-f][1,2,4]triazepino[2,3-a]benzimidazole and 10-amino-2-methyl-4-oxo pyrimido[1,2-a]benzimidazole derivatives

  • Youness El Bakri
  • El Hassane Anouar
  • Ilias Marmouzi
  • Karima Sayah
  • Youssef Ramli
  • My El Abbes Faouzi
  • El Mokhtar Essassi
  • Joel T. Mague
Original Paper
  • 84 Downloads

Abstract

Diabetes affects a large population of the globe and is considered as a leading cause of death. Many synthetic and natural inhibitors have been developed for diabetes treatment. Herein, we report the potential antidiabetic activity of two new heterocyclic systems, namely 3.6-dimethyl-5-oxo-pyrido[3,4f][1,2,4]triazepino[2,3-a]benzimidazole (I) and 10-amino-2-methyl-4-oxo pyrimido[1,2-a]benzimidazole (II) against three related enzymes: α-amylase, α-glucosidase and β-galactosidase. Compounds I and II were synthesized by the action of DMF-DMA and dimethyl sulfate in the presence of water on 2-methyl-3H-benzimidazolo[1,2b][1,2,4]triazepin-4(5H)-one, and are characterized by single X-ray diffraction. The binding interaction modes in the active sites of I and II and targeted enzymes (stable complexes ligand-receptor) are emphasized using the molecular docking approach by applying the Lamarckian genetic algorithm method. Furthermore, plausible mechanisms have been proposed explaining their synthesis. Hirshfeld surface analysis reveals the nature of molecular interactions and fingerprint plots provide information about the percentage contribution from each individual molecular contact to the structure surface.

Graphical abstract

Left Molecular packing of 1,4-dimethyl-2-oxo-pyrimido[1,2-a]benzimidazole hydrate. Right Docking active site of α-glucosidase

Keywords

Benzimidazole Antidiabetic activity X-ray Hydrogen bond Hirshfeld surface Molecular docking 

Supplementary material

894_2018_3705_MOESM1_ESM.docx (259 kb)
ESM 1 (DOCX 259 kb)
894_2018_3705_MOESM2_ESM.docx (24 kb)
ESM 2 (DOCX 21 kb)

References

  1. 1.
    Kayarohanam S, Kavimani S (2015) Current trends of plants having antidiabetic activity: a review. J Bioanal Biomed 7:55–65CrossRefGoogle Scholar
  2. 2.
    Benalla W, Bellahcen S, Bnouham M (2010) Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors. Curr Diabetes Rev 6:247–254CrossRefGoogle Scholar
  3. 3.
    Rahimi M (2015) A review: anti diabetic medicinal plants used for diabetes mellitus. Bull Environ Pharmacol Life Sci 4:163–180Google Scholar
  4. 4.
    Das A, Rai M (2008) A world without diabetes and its complications: a preventive program. Type 2:1Google Scholar
  5. 5.
    Sheldrick G (2014) SHELXTL Version 2014/7. Program for crystal structure refinement, University of GöttingenGoogle Scholar
  6. 6.
    Marmouzi I, El Karbane M, El Hamdani M, Kharbach M, Naceiri Mrabti H, Alami R, Dahraoui S, El Jemli M, Ouzzif Z, Cherrah Y (2017) Phytochemical and pharmacological variability in golden thistle functional parts: comparative study of roots, stems, leaves and flowers. Nat Prod Res 31:1–6CrossRefGoogle Scholar
  7. 7.
    Li P-H, Lin Y-W, Lu W-C, Hu J-M, Huang D-W (2016) In vitro hypoglycemic activity of the phenolic compounds in longan fruit (Dimocarpus longan var. Fen Ke) shell against α-glucosidase and β-galactosidase. Int J Food Prop 19:1786–1797CrossRefGoogle Scholar
  8. 8.
    Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785–2791CrossRefGoogle Scholar
  9. 9.
    Shen X, Saburi W, Gai Z, Kato K, Ojima-Kato T, Yu J, Komoda K, Kido Y, Matsui H, Mori H (2015) Structural analysis of the α-glucosidase HaG provides new insights into substrate specificity and catalytic mechanism. Acta Crystallogr D 71:1382–1391CrossRefGoogle Scholar
  10. 10.
    Abuelizz HA, Dib RE, Marzouk M, Anouar E, Maklad Y, Attia H, Al-Salahi R (2017) Molecular docking and anticonvulsant activity of newly synthesized quinazoline derivatives. Molecules 22:1094–1103CrossRefGoogle Scholar
  11. 11.
    Cremer D, Pople JA (1975) General definition of ring puckering coordinates. J Am Chem Soc 97:1354–1358Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Youness El Bakri
    • 1
  • El Hassane Anouar
    • 2
  • Ilias Marmouzi
    • 3
  • Karima Sayah
    • 3
  • Youssef Ramli
    • 4
  • My El Abbes Faouzi
    • 3
  • El Mokhtar Essassi
    • 1
  • Joel T. Mague
    • 5
  1. 1.Laboratoire de Chimie Organique Hétérocyclique, Centre de Recherche des Sciences des Médicaments, Pôle de Compétences Pharmacochimie, URAC 21, Faculté des SciencesMohammed V University in RabatRabatMorocco
  2. 2.Department of Chemistry, College of Science and HumanitiesPrince Sattam bin Abdulaziz UniversityAlKharjSaudi Arabia
  3. 3.Faculté de Médicine et de Pharmacie, Laboratoire de Pharmacologie et Toxicologie, équipe de PharmacocinétiqueUniversity Mohammed V in RabatRabatMorocco
  4. 4.Medicinal Chemistry Laboratory, Faculty of Medicine and PharmacyMohammed V University in RabatRabatMorocco
  5. 5.Department of ChemistryTulane UniversityNew OrleansUSA

Personalised recommendations