Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs
A series of methyl β-D-galactopyranoside (MGP, <b>1</b>) analogs were selectively acylated with cinnamoyl chloride in anhydrous <i>N</i>,<i>N</i>-dimethylformamide/triethylamine to yield 6-<i>O</i>-substitution products, which was subsequently converte...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/b8c474d5693f443ea778beb6a7bcf6a7 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:b8c474d5693f443ea778beb6a7bcf6a7 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:b8c474d5693f443ea778beb6a7bcf6a72021-11-25T18:29:12ZSynthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs10.3390/molecules262270161420-3049https://doaj.org/article/b8c474d5693f443ea778beb6a7bcf6a72021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/7016https://doaj.org/toc/1420-3049A series of methyl β-D-galactopyranoside (MGP, <b>1</b>) analogs were selectively acylated with cinnamoyl chloride in anhydrous <i>N</i>,<i>N</i>-dimethylformamide/triethylamine to yield 6-<i>O</i>-substitution products, which was subsequently converted into 2,3,4-tri-<i>O</i>-acyl analogs with different acyl halides. Analysis of the physicochemical, elemental, and spectroscopic data of these analogs revealed their chemical structures. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) showed promising antifungal functionality comparing to their antibacterial activities. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests were conducted for four compounds (<b>4</b>, <b>5</b>, <b>6</b>, and <b>9</b>) based on their activity. MTT assay showed low antiproliferative activity of compound <b>9</b> against Ehrlich’s ascites carcinoma (EAC) cells with an IC<sub>50</sub> value of 2961.06 µg/mL. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties whereas molecular docking identified potential inhibitors of the SARS-CoV-2 main protease (6Y84). A 150-ns molecular dynamics simulation study revealed the stable conformation and binding patterns in a stimulating environment. In-silico ADMET study suggested all the designed molecules to be non-carcinogenic, with low aquatic and non-aquatic toxicity. In summary, all these antimicrobial, anticancer and in silico studies revealed that newly synthesized MGP analogs possess promising antiviral activity, to serve as a therapeutic target for COVID-19.Md. Ruhul AminFarhana YasminMohammed Anowar HosenSujan DeyShafi MahmudMd. Abu SalehTalha Bin EmranImtiaj HasanYuki FujiiMasao YamadaYasuhiro OzekiSarkar Mohammad Abe KawsarMDPI AGarticlemethyl β-D-galactopyranosidesynthesisPASSmolecular dockingmolecular dynamicsPharmacokineticOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 7016, p 7016 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
methyl β-D-galactopyranoside synthesis PASS molecular docking molecular dynamics Pharmacokinetic Organic chemistry QD241-441 |
| spellingShingle |
methyl β-D-galactopyranoside synthesis PASS molecular docking molecular dynamics Pharmacokinetic Organic chemistry QD241-441 Md. Ruhul Amin Farhana Yasmin Mohammed Anowar Hosen Sujan Dey Shafi Mahmud Md. Abu Saleh Talha Bin Emran Imtiaj Hasan Yuki Fujii Masao Yamada Yasuhiro Ozeki Sarkar Mohammad Abe Kawsar Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs |
| description |
A series of methyl β-D-galactopyranoside (MGP, <b>1</b>) analogs were selectively acylated with cinnamoyl chloride in anhydrous <i>N</i>,<i>N</i>-dimethylformamide/triethylamine to yield 6-<i>O</i>-substitution products, which was subsequently converted into 2,3,4-tri-<i>O</i>-acyl analogs with different acyl halides. Analysis of the physicochemical, elemental, and spectroscopic data of these analogs revealed their chemical structures. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) showed promising antifungal functionality comparing to their antibacterial activities. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests were conducted for four compounds (<b>4</b>, <b>5</b>, <b>6</b>, and <b>9</b>) based on their activity. MTT assay showed low antiproliferative activity of compound <b>9</b> against Ehrlich’s ascites carcinoma (EAC) cells with an IC<sub>50</sub> value of 2961.06 µg/mL. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties whereas molecular docking identified potential inhibitors of the SARS-CoV-2 main protease (6Y84). A 150-ns molecular dynamics simulation study revealed the stable conformation and binding patterns in a stimulating environment. In-silico ADMET study suggested all the designed molecules to be non-carcinogenic, with low aquatic and non-aquatic toxicity. In summary, all these antimicrobial, anticancer and in silico studies revealed that newly synthesized MGP analogs possess promising antiviral activity, to serve as a therapeutic target for COVID-19. |
| format |
article |
| author |
Md. Ruhul Amin Farhana Yasmin Mohammed Anowar Hosen Sujan Dey Shafi Mahmud Md. Abu Saleh Talha Bin Emran Imtiaj Hasan Yuki Fujii Masao Yamada Yasuhiro Ozeki Sarkar Mohammad Abe Kawsar |
| author_facet |
Md. Ruhul Amin Farhana Yasmin Mohammed Anowar Hosen Sujan Dey Shafi Mahmud Md. Abu Saleh Talha Bin Emran Imtiaj Hasan Yuki Fujii Masao Yamada Yasuhiro Ozeki Sarkar Mohammad Abe Kawsar |
| author_sort |
Md. Ruhul Amin |
| title |
Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs |
| title_short |
Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs |
| title_full |
Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs |
| title_fullStr |
Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs |
| title_full_unstemmed |
Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs |
| title_sort |
synthesis, antimicrobial, anticancer, pass, molecular docking, molecular dynamic simulations & pharmacokinetic predictions of some methyl β-d-galactopyranoside analogs |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/b8c474d5693f443ea778beb6a7bcf6a7 |
| work_keys_str_mv |
AT mdruhulamin synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT farhanayasmin synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT mohammedanowarhosen synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT sujandey synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT shafimahmud synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT mdabusaleh synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT talhabinemran synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT imtiajhasan synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT yukifujii synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT masaoyamada synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT yasuhiroozeki synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs AT sarkarmohammadabekawsar synthesisantimicrobialanticancerpassmoleculardockingmoleculardynamicsimulationspharmacokineticpredictionsofsomemethylbdgalactopyranosideanalogs |
| _version_ |
1718411100387540992 |