Investigation of biological activity of 2,3-disubstituted quinazolin-4(1H)-ones against Mycobacterium tuberculosis and DNA via docking, spectroscopy and DFT studies

Kumar, C.B. Pradeep; Raghu, M.S.; Prasad, K. N. N.; Chandrasekhar, S.; Jayanna, B.K.; Alharthi, Fahad A.; Prashanth, M.K.; Kumar, K. Deva Arun

doi:10.1039/d0nj03800h

Cited by 38 publications

(8 citation statements)

References 48 publications

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“…The Pearson principle of maximum hardness states that the chemical hardness inversely affects reactivity. Compounds with reduced chemical hardness and higher softness are considered to be more reactive . A higher electronegativity (χ), electrophilicity indices, and chemical potentials correspond to a greater chemical reactivity with catalytic proteins as they serve as good electrophiles rather than nucleophiles .…”

Section: Results and Discussionmentioning

confidence: 99%

“…The given equation was employed to determine the ionization potential (IP), electron affinity (EA), as well as quantum mechanical parameters such as global hardness (η), global softness ( S ), electronegativity (χ), electrophilicity index (ω), and chemical potential (μ). , …”

Section: Materials and Methodologymentioning

confidence: 99%

“…Compounds with reduced chemical hardness and higher softness are considered to be more reactive. 51 A higher electronegativity (χ), electrophilicity indices, and chemical potentials correspond to a greater chemical reactivity with catalytic proteins as they serve as good electrophiles rather than nucleophiles. 52 Similarly, the electrophilicity index (ω) quantifies a molecule's electron-accepting capacity and the chemical potential (μ) indicates the path of electron transfer.…”

Section: Hydrogen Bondsmentioning

confidence: 99%

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In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

Raut,

Upadhyaya,

Bashyal

et al. 2023

ACS Omega

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Human pancreatic α-amylase (HPA), situated at the apex of the starch digestion hierarchy, is an attractive therapeutic approach to precisely regulate blood glucose levels, thereby efficiently managing diabetes. Polyphenols offer a natural and multifaceted approach to moderate postprandial sugar spikes, with their slight modulation in carbohydrate digestion and potential secondary benefits, such as antioxidant and antiinflammatory effects. Taking into consideration the unfavorable side effects of currently available commercial medications, we aimed to study a library of polyphenols attributed to their remarkable antidiabetic properties and screened the most potent HPA inhibitor via a comprehensive in silico study encompassing molecular docking, molecular mechanics with generalized Born and surface area solvation (MM/GBSA) calculation, molecular dynamics (MD) simulation, density functional theory (DFT) study, and pharmacokinetic properties followed by an in vitro assay. Significant hydrogen bonding with the catalytic triad residues of HPA, prominent MM/ GBSA binding energy of −27.03 kcal/mol, and the stable nature of the protein−ligand complex with regard to 100 ns MD simulation screened quercetin as the best HPA inhibitor. Additionally, quercetin showed strong reactivity in the substrate-binding pocket of HPA and exhibited favorable pharmacokinetic properties with a considerable inhibitory concentration (IC 50 ) of 57.37 ± 0.9 μg/mL against α-amylase. This study holds prospects for HPA inhibition and suggests quercetin as an approach to therapy for diabetes; however, it is imperative to conduct further research.

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Section: Results and Discussionmentioning

confidence: 99%

Section: Materials and Methodologymentioning

confidence: 99%

Section: Hydrogen Bondsmentioning

confidence: 99%

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In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

Raut,

Upadhyaya,

Bashyal

et al. 2023

ACS Omega

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“…The use of global reactivity descriptors is common in predicting the activity of antimicrobial compounds [41][42][43][44]. For example, the electrophilicity index, ω, has been used in the evaluation of the toxicity of molecules with anti-microbial activity, allowing the quantification of the drug-receptor biological interaction [45].…”

Section: Global Reactivity Indicesmentioning

confidence: 99%

Implicit and Explicit Solvent Effects on the Global Reactivity and the Density Topological Parameters of the Preferred Conformers of Caespitate

Moreno-Ceballos,

Castro,

Caballero

et al. 2024

Computation

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In the search to cover the urgent need to combat infectious diseases, natural products have gained attention in recent years. The caespitate molecule, isolated from the plant Helichrysum caespititium of the Asteraceae family, is used in traditional African medicine. Caespitate is an acylphloroglucinol with biological activity. Acylphloroglucinols have attracted attention for treating tuberculosis due to their structural characteristics, highlighting the stabilizing effect of their intramolecular hydrogen bonds (IHBs). In this work, a conformational search for the caespitate was performed using the MM method. Posteriorly, DFT calculations with the APFD functional were used for full optimization and vibrational frequencies, obtaining stable structures. A population analysis was performed to predict the distribution of the most probable conformers. The calculations were performed in the gas phase and solution using the implicit SMD model for water, chloroform, acetonitrile, and DMSO solvents. Additionally, the multiscale ONIOM QM1/QM2 model was used to simulate the explicit solvent. The implicit and explicit solvent effects were evaluated on the global reactivity indexes using the conceptual-DFT approach. In addition, the QTAIM approach was applied to analyze the properties of the IHBs of the most energetically and populated conformers. The obtained results indicated that the most stable and populated conformer is in the gas phase, and chloroform has an extended conformation. However, water, acetonitrile, and DMSO have a hairpin shape. The optimized structures are well preserved in explicit solvent and the interaction energies for the IHBs were lower in explicit than implicit solvents due to non-covalent interactions formed between the solvent molecules. Finally, both methodologies, with implicit and explicit solvents, were validated with 1H and 13C NMR experimental data. In both cases, the results agreed with the experimental data reported in the CDCl3 solvent.

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“…Microbial strains were cultivated overnight at 37 °C in nutrients and potato dextrose agar medium. The antibacterial activity and minimum inhibitory concentration (MIC) of the ligand and its metal complexes were assessed using agar disc diffusion 7 and broth dilution techniques 8 , respectively. The inhibitory zone was measured in millimeters for all samples evaluated in triplicate.…”

Section: Antimicrobial Activitymentioning

confidence: 99%

Untitled

2021

IJPSR

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New pharmacologically active transition metal complexes of Co(II), Ni (II), Cu (II), and Zn(II) have been synthesized with the ligand 5-. Different analytical and spectroscopic tools were used to analyze the compounds, including elemental analysis, FTIR, 1H-NMR, mass spectra, electronic spectra, magnetic measurement, and molar conductance techniques. FTIR confirmed that the ligand coordinates the metal ion to form a mononuclear complex via the oxygen and nitrogen atoms of the phenolic and quinoline rings. For Co(II) and Zn(II) complexes, tetrahedral geometry is recommended, whereas square-planar geometry is proposed for Ni(II) and Cu(II) complexes. The antibacterial activity of the ligand and its metal complexes were assessed using the disc diffusion method, and minimum inhibitory concentration (MIC) was determined in the broth dilution technique. The antimicrobial activity results showed that the metal complexes were shown to be more active than the free ligand. Besides, Cu(II) complex was shown to be the most potent antioxidant using the DPPH and hydroxyl radical scavenging methods, with IC50 values of 17.3 and 21.5 μg/mL, respectively.

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Investigation of biological activity of 2,3-disubstituted quinazolin-4(1H)-ones against Mycobacterium tuberculosis and DNA via docking, spectroscopy and DFT studies

Abstract: A series of 2,3-disubstituted quinazolin-4(1H)-ones (3a-j) were screened for their antimicrobial activity using the minimum inhibitory concentration method (MIC). The in vitro anti-tubercular (TB) activity of compounds against Mycobacterium tuberculosis...

Cited by 38 publications

References 48 publications

In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor

Implicit and Explicit Solvent Effects on the Global Reactivity and the Density Topological Parameters of the Preferred Conformers of Caespitate

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