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. 2022 Jul 11;16(1):53.
doi: 10.1186/s13065-022-00844-8.

New solid phase methodology for the synthesis of biscoumarin derivatives: experimental and in silico approaches

Elham Zarenezhad  1 , Mohammad Nazari Montazer  2 , Masoumeh Tabatabaee  3 , Cambyz Irajie  4 , Aida Iraji  5   6
Affiliations

New solid phase methodology for the synthesis of biscoumarin derivatives: experimental and in silico approaches

Elham Zarenezhad et al. BMC Chem. .

Abstract

The simple and greener one-pot approach for the synthesis of biscoumarin derivatives using catalytic amounts of nano-MoO3 catalyst under mortar-pestle grinding was described. The use of non-toxic and mild catalyst, cost-effectiveness, ordinary grinding, and good to the excellent yield of the final product makes this procedure a more attractive pathway for the synthesis of biologically remarkable pharmacophores. Accordingly, biscoumarin derivatives were successfully extended in the developed protocols. Next, a computational investigation was performed to identify the potential biological targets of this set of compounds. In this case, first, a similarity search on different virtual libraries was performed to find an ideal biological target for these derivatives. Results showed that the synthesized derivatives can be α-glucosidase inhibitors. In another step, molecular docking studies were carried out against human lysosomal acid-alpha-glucosidase (PDB ID: 5NN8) to determine the detailed binding modes and critical interactions with the proposed target. In silico assessments showed the gold score value in the range of 17.56 to 29.49. Additionally, molecular dynamic simulations and the MM-GBSA method of the most active derivative against α-glucosidase were conducted to study the behavior of selected compounds in the biological system. Ligand 1 stabilized after around 30 ns and participated in various interactions with Trp481, Asp518, Asp616, His674, Phe649, and Leu677 residues.

Keywords: Biscoumarin; MM-GBSA; MoO3-nanoparticle; Molecular dynamics simulations.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Natural coumarin compounds
Fig. 2
Fig. 2
coumarin derivatives drugs
Fig. 3
Fig. 3
PXRD patterns of the synthesized MoO3 nano-crystals
Fig. 4
Fig. 4
Scanning electron micrographs for prepared nano-MoO3
Fig. 5
Fig. 5
General pathway for synthesis of biscoumarin derivatives
Fig. 6
Fig. 6
A plausible mechanism for synthesis of biscoumarins derivatives using MoO3
Fig. 7
Fig. 7
Docking conformations of compounds 1–14 (orange stick) in the α-glucosidase active site. Hydrogen bonds are depicted in green dashed lines, π-π stacked interactions are depicted in dark pink dashed lines, π-aryl interactions are depicted in pink dashed lines pi-sulfur interactions are depicted in pale orange dashed lines and and pi-anion interactions are depicted in dark orange dashed lines
Fig. 7
Fig. 7
Docking conformations of compounds 1–14 (orange stick) in the α-glucosidase active site. Hydrogen bonds are depicted in green dashed lines, π-π stacked interactions are depicted in dark pink dashed lines, π-aryl interactions are depicted in pink dashed lines pi-sulfur interactions are depicted in pale orange dashed lines and and pi-anion interactions are depicted in dark orange dashed lines
Fig. 8
Fig. 8
RMSD plot of the enzyme in complexed compound 1 in the MD simulation time. RMSD values of the Ca atoms of the protein are depicted in blue, and ligand-complex values are exhibited in red
Fig. 9
Fig. 9
RMSF plot of the α-glucosidase residue in complexed with compound 1
Fig. 10
Fig. 10
Protein–ligand contacts during the whole simulation time in α-glucosidase complexed with compound 1
Fig. 11
Fig. 11
2D representation of ligand-residue interactions
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