In silico DFT study, molecular docking, and ADMET predictions of cytidine analogs with antimicrobial and anticancer properties

Rana, Kazi Masud; Maowa, Jannatul; Alam, Asraful; Dey, Sujan; Hosen, Anowar; Hasan, Imtiaj; Fujii, Yuki; Ozeki, Yasuhiro; Kawsar, Sarkar M. A.

doi:10.1007/s40203-021-00102-0

Cited by 43 publications

(42 citation statements)

References 53 publications

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“…The 13 C-NMR spectrum also showed the presence of one cinnamoyl group by displaying the following expected resonance peaks: δ 164.81 (C6H5CH=CHCO-), 151.52 This compound (2) was sufficiently pure for the next reactions to synthesize analogs 3-10 (Figure S1). The structure of the cinnamoyl derivative (2) was established by analyzing its elemental data, FTIR, and 1 H-NMR spectra.…”

Section: Characterizationmentioning

confidence: 94%

“…The 13 C-NMR spectrum also showed the presence of one cinnamoyl group by displaying the following expected resonance peaks: δ 164.81 (C 6 H 5 CH=CHCO-), 151. (2) can be explained by attachment of cinnamoyl group to the more reactive and less sterically hindered primary -OH group at the C-6 position, with consequent formation of methyl 6-O-cinnamoyl-β-D-galactopyranoside (2) as sole product.…”

Section: Characterizationmentioning

confidence: 98%

“…6-O-Cinnamoyl derivative 2 was also similarly reacted with several fatty acid derivatives such as hexanoyl chloride, lauroyl chloride, myristoyl chloride, and palmitoyl chloride in dry DMF/Et 3 N to afford 2,3,4-tri-O-hexanoyl-β-Dgalactopyranoside (4), 2,3,4-tri-O-lauroyl-β-D-galactopyranoside (5), 2,3,4-tri-O-myristoylβ-D-galactopyranoside (6), and 2,3,4-tri-O-palmitoyl-β-D-galactopyranoside (7) with good yields, respectively. The structures of these derivatives were ascertained by complete interpretation of their IR, 1 H-NMR, 13 C-NMR, mass, elemental analysis. Final confirmation of the structure of the cinnamoyl derivative 2 was carried out by conversion of its trityl derivative (8), 4-nitrobenzoyl derivative (9), and 4-bromobenzoyl derivative (10).…”

Section: Characterizationmentioning

confidence: 99%

“…The 1 H-NMR spectrum of compound 10 showed the two six-aromatic proton multiplets at δ 8.01 (as m) and δ 7.93 (as m), which are characteristic of the p-substituted benzoyl group. Furthermore, the deshielding of C-2, C-3, and C-4 protons from their usual values (compound 2) and the resonance of other protons in their anticipated positions, 13 C-NMR, and mass spectra confirmed the structure of this compound as methyl 2,3,4-tri-O-(4-bromobenzoyl)-6-O-cinnamoyl-β-D-galactopyranoside (10). Furthermore, these acylation products and their derivatives were found to have a long shelf life.…”

Section: Characterizationmentioning

confidence: 99%

“…It was found from the literature survey that a large number of biologically active compounds also possess aromatic, heteroaromatic, and acyl substituents [5][6][7][8][9][10][11][12]. For example, the benzene substituted benzene, and nitrogen, sulfur, and halogen-containing substituents are known to enhance the biological activity of the parent compound [13][14][15][16]. If an active nucleus is linked to another active nucleus, the resulting molecule may possess greater potential for biological activity [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs

et al. 2021

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A series of methyl β-D-galactopyranoside (MGP, 1) analogs were selectively acylated with cinnamoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to yield 6-O-substitution products, which was subsequently converted into 2,3,4-tri-O-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 (4, 5, 6, and 9) based on their activity. MTT assay showed low antiproliferative activity of compound 9 against Ehrlich’s ascites carcinoma (EAC) cells with an IC50 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.

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Section: Characterizationmentioning

confidence: 94%

Section: Characterizationmentioning

confidence: 98%

Section: Characterizationmentioning

confidence: 99%

Section: Characterizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs

et al. 2021

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Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 1,3,4‐Thiadiazole Derivatives as Potent Antimicrobial Agents

Çevik

Çeli̇k

İnce

et al. 2023

Chemistry & Biodiversity

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In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using 1 H-NMR, 13 C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g, respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds' theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f.

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Nucleoside‐Based Drug Target with General Antimicrobial Screening and Specific Computational Studies against SARS‐CoV‐2 Main Protease

Kawsar,

Hossain,

Saha

et al. 2024

ChemistrySelect

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This review article aims to significantly advance the scientific community's efforts to develop effective nucleoside‐based drugs for treating severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and other emerging infectious diseases. This study concentrates on the main viral protease (Mpro) and explores nucleoside‐based compounds as potential therapeutic agents. This investigation investigated the impact of acylation‐induced modifications on the nucleoside hydroxyl group and subsequent properties. Nucleoside analogs, which are recognized for their diverse biochemical properties, were synthesized and rigorously screened to evaluate their antimicrobial efficacy. In the domain of pharmaceutical research, computational pharmacokinetics has emerged as a critical tool, especially in the pursuit of nucleoside analogs as potential therapeutics. In silico methods aid in predicting pharmacokinetic traits, interactions with crucial enzymes, and the stability of these analogs in biological environments, thereby streamlining drug design and reducing experimental costs. Concurrently, computational studies revealed the intricate interactions between the analogs and the active site of the main protease. The amalgamation of experimental screening and computational insights underscores the emergence of potent nucleoside candidates with inhibitory activity against SARS‐CoV‐2 Mpro. Additionally, this review integrates computational studies that provide valuable insights into the interactions between nucleoside analogs and the main protease of SARS‐CoV‐2.

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In silico DFT study, molecular docking, and ADMET predictions of cytidine analogs with antimicrobial and anticancer properties

Cited by 43 publications

References 53 publications

Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs

Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs

Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 1,3,4‐Thiadiazole Derivatives as Potent Antimicrobial Agents

Nucleoside‐Based Drug Target with General Antimicrobial Screening and Specific Computational Studies against SARS‐CoV‐2 Main Protease

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