| Autor: |
Ahmmed F; Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh., Islam AU; Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh., Mukhrish YE; Department of Chemistry, Faculty of Science, Jazan University, Jazan 45142, Saudi Arabia., Bakri YE; Department of Theoretical and Applied Chemistry, South Ural State University, Lenin Prospect 76, 454080 Chelyabinsk, Russia., Ahmad S; Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan., Ozeki Y; School of Sciences, Yokohama City University, 22-2, Seto, Yokohama 236-0027, Japan., Kawsar SMA; Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh. |
| Jazyk: |
angličtina |
| Zdroj: |
Molecules (Basel, Switzerland) [Molecules] 2022 Dec 26; Vol. 28 (1). Date of Electronic Publication: 2022 Dec 26. |
| DOI: |
10.3390/molecules28010219 |
| Abstrakt: |
The chemistry and biochemistry of carbohydrate esters are essential parts of biochemical and medicinal research. A group of methyl β-d-galactopyranoside (β-MGP, 1) derivatives was acylated with 3-bromobenzoyl chloride and 4-bromobenzoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to obtain 6-O-substitution products, which were subsequently converted into 2,3,4-tri-O-acyl derivatives with different aliphatic and aromatic substituents. Spectroscopic and elemental data exploration of these derivatives confirmed their chemical structures. In vitro biological experiments against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) revealed ascending antifungal and antibacterial activities compared with their antiviral activities. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were performed for two derivatives, 3 and 9, based on their antibacterial activities. Most of these derivatives showed >780% inhibition of fungal mycelial growth. Density functional theory (DFT) was used to calculate the chemical descriptors and thermodynamic properties, whereas molecular docking was performed against antibacterial drug targets, including PDB: 4QDI, 5A5E, 7D27, 1ZJI, 3K8E, and 2MRW, and antifungal drug targets, such as PDB: 1EA1 and 1AI9, to identify potential drug candidates for microbial pathogens. A 100 ns molecular dynamics simulation study revealed stable conformation and binding patterns in a stimulating environment by their uniform RMSD, RMSF, SASA, H-bond, and RoG profiles. In silico pharmacokinetic and quantitative structure−activity relationship (QSAR) calculations (pIC50 values 3.67~8.15) suggested that all the designed β-MGP derivatives exhibited promising results due to their improved kinetic properties with low aquatic and non-aquatic toxicities. These biological, structure−activity relationship (SAR) [lauroyl-(CH3(CH2)10CO-) group was found to have potential], and in silico computational studies revealed that the newly synthesized MGP derivatives are potential antibacterial/antifungal candidates and can serve as therapeutic targets for human and plant pathogens. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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