Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach

Arshad, Uzma; Ahmed, Sibtain; Shafiq, Nusrat; Ahmad, Zaheer; Hassan, A.E.H.; Akhtar, Naseem; Parveen, Shahida; Mehmood, Tahir

doi:10.3390/molecules26154424

Cited by 11 publications

(5 citation statements)

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“…Isolated compounds were checked for their potential as antioxidants and diabetic inhibitors by standard procedures. , Results of antidiabetic (Figure ) revealed that the compound HR5 was an excellent diabetic inhibitor with a minimum inhibition concentration (IC 50 ) of 11.69 μM, while antioxidant results (Figure ) revealed the compounds HR3 and HR5 as excellent inhibitors with IC 50 = 15.14 μM and 15.64 μM, respectively, as shown in graph (Figure ).…”

Section: Resultsmentioning

confidence: 99%

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Plant-Based Bioactive Phthalates Derived fromHibiscus rosa-sinensis: As In Vitro and In Silico Enzyme Inhibition

Yasmin,

Nazli,

Shafiq

et al. 2023

ACS Omega

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Hibiscus rosa-sinensis is an attractive, ever-blossoming, and effortlessly available plant around the globe. The fabulous flowers of H. rosa-sinensis enjoy a significant status in folk medicine throughout the world and comprise a range of phyto constituents due to which this splendid flower owns numerous biological and pharmaceutical activities like antioxidant, antifungal, antimicrobial, anti-inflammatory, antipyretic, antidiabetic, and antifertility activity. Considering this, column chromatographic isolation of the phytoconstituents of ethyl acetate fraction of the flowers of H. rosa-sinensis was performed. A series of five phthalates including Di- n -octyl phthalate ( HR1 ), ditridecyl phthalate ( HR2 ), 1-allyl 2-ethyl phthalate ( HR3 ), diethyl phthalate ( HR4 ), and bis (6-methylheptyl) phthalate ( HR5 ) were isolated. The structures of the isolated phthalates were elucidated by gas chromatography–mass spectrometry, 1 H NMR, and 13 C NMR. In silico and in vitro antidiabetic and antioxidant potential and DFT studies of isolated phthalates were carried out. In our study, isolated ligands were explored as potent antidiabetic as well as antioxidant agents as they exhibited good binding affinity (in in vitro and in silico experiments) against all selected protein targets. Compounds HR1–HR5 showed that the binding affinity value ranged from −5.9 to −5.2 kcal/mol, −5.5 to −4.3 kcal/mol, and −5.0 to −4.1 kcal/mol for target proteins 1HNY , 2I3Y , and 5O40 , respectively. Among all isolated phthalates, HR5 can be a lead compound as it showed the best binding affinity with human pancreatic α-amylase (Δ G = −5.9 kcal/mol) and displayed a minimum inhibition concentration (IC 50 ) of 11.69 μM among all phthalates. Compound HR1 was the best docked and scored compound for inhibiting glutathione peroxidase; however, HR2 possessed the lowest binding score of −5.0 kcal/mol, thus indicating the highest potential among isolated phthalates for inhibiting the superoxide dismutase. Furthermore, the top-ranked docked ligand–protein complex for each protein was assessed for stability of protein and complex mobility by molecular dynamics simulation using the IMOD server.

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Section: Resultsmentioning

confidence: 99%

“…In vitro, the antidiabetic activity of isolated compounds ( HR1–HR5 ) was assessed by utilizing starch and α-amylase as the substrate and enzyme, respectively. Acarbose was taken as a standard drug. ,– …”

Section: Methodsmentioning

confidence: 99%

Plant-Based Bioactive Phthalates Derived fromHibiscus rosa-sinensis: As In Vitro and In Silico Enzyme Inhibition

Yasmin,

Nazli,

Shafiq

et al. 2023

ACS Omega

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“…The binding location and grid resolution was adjusted to 0.3Å, search algorithm was set on energy minimization. The pose with top docked orientation was inspected utilizing MolDock Score [GRID] algorithm, for the population size of 50, 1500 were the maximum iterations, number of runs taken were 10 and energy threshold of 100 12 . The whole data of docking analysis of all ligands as parameters like MolDock score, bond category, bond type, bond length, and interacting residues is tabulated in Tables 4-5.…”

Section: Gcms Analysismentioning

confidence: 99%

“…As χ = -CP, so chemical potential is related to electron removal tendency of a molecule. Smaller (χ) value and larger (CP) value indicates the delocalization of electrons, therefore a molecule with low (χ) and high (CP) can be more comfortably interact with biological scheme (more reactive) 12 . Electronegativity and chemical potentialbased activity ranking of under studied compounds is below; 10>6 > 8> 9>7 >2> 1> 3 The hardness (η) and softness (S) of a chemical compound is directly associated with ΔE.The hardness denotes the resistance of compound toward the distortion of the electron cloud of chemical system during chemical reaction.…”

Section: Molecular Docking Assessment For Anti-oxidant Potentialmentioning

confidence: 99%

Identification of Phthalates, Methyl Esters and Siloxanes through GCMS analysis, biological investigation, DFT and Molecular Docking studies on Methanolic Subfractions of Hibiscus Rosa Sinensis flower extract

Yasmin,

Nazli,

Shafiq

et al. 2023

PJMHS

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Purpose: Plants are vital source of bioactive molecules, so they play a significant role in prevention and curing of various health disorders. The Hibiscus rosa sinensis, an ornate with attractive flowers, has conventionally been utilized globally as a curative agent for a wide range of ailments. Methods: In current study, we prepared crude methanolic extract of flowers of Hibiscus rosa sinensis and subjected that to in vitro biological evaluation to assess its antidiabetic and antioxidant potential. Outcomes of in vitro evaluation confirmed the excellent antidiabetic and antioxidant potency of Hibiscus flowers. Further crude methanolic extract was fractionated to hexane, ethyl acetate and methanol fractions. Among the three fractions, we subjected methanolic fraction to GCMS analysis to explore the bioactive molecules contained by this fraction. Results: The spectral data obtained from GCMS analysis revealed the existence of a total of 12 compounds including phthalates, methyl esters and siloxanes which are known to have a range of reported pharmacological activities. Successively, we subjected the identified molecules to molecular docking to assess their antidiabetic and antioxidant potential and DFT study to explore the reactivity of their molecular structures. As far as we are aware, it is the first report on the in-silico antidiabetic (128.1µM) and antioxidant (410.0µM) potential assessment of phytoconstituents of methanolic extract of floral part of Hibiscus rosa sinensis. The results revealed the H. Sinensis plat as more viable and good alternative to existing natural remedies.

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“…The Computer-aided drug design (CADD) can not only preliminarily predict the activity of inhibitors, but also save experimental costs and provide guidance for designing more effective inhibitors by exploring the structure–activity relationship of inhibitors at the molecular level 32 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of antibacterial, cytotoxicity, and apoptosis activity of novel chromene-sulfonamide hybrids synthesized under solvent-free conditions and 3D-QSAR modeling studies

Ghomashi,

Damavandi

et al. 2024

Sci Rep

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In this study, eleven novel chromene sulfonamide hybrids were synthesized by a convenient method in accordance with green chemistry. At first, chromene derivatives (1–9a) were prepared through the multi-component reaction between aryl aldehydes, malononitrile, and 3-aminophenol. Then, synthesized chromenes were reacted with appropriate sulfonyl chlorides by grinding method to give the corresponding chromene sulfonamide hybrids (1–11b). Synthesized hybrids were obtained in good to high yield and characterized by IR, 1HNMR, 13CNMR, CHN and melting point techniques. In addition, the broth microdilution assay was used to determine the minimal inhibitory concentration of newly synthesized chromene-sulfonamide hybrids. The MTT test was used to determine the cytotoxicity and apoptotic activity of the newly synthesized compounds against fibroblast L929 cells. The 3D‑QSAR analysis confirmed the experimental assays, demonstrating that our predictive model is useful for developing new antibacterial inhibitors. Consequently, molecular docking studies were performed to validate the findings of the 3D-QSAR analysis, confirming the potential binding interactions of the synthesized chromene-sulfonamide hybrids with the target enzymes. Molecular docking studies were employed to support the 3D-QSAR predictions, providing insights into the binding interactions between the newly synthesized chromene-sulfonamide hybrids and their target bacterial enzymes, thereby reinforcing the potential efficacy of these compounds as antibacterial agents. Also, some of the experimental outcomes supported or conflicted with the pharmacokinetic prediction (especially about compound carcinogenicity). The performance of ADMET predictor results was assessed. The work presented here proposes a computationally driven strategy for designing and discovering a new sulfonamide scaffold for bacterial inhibition.

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Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach

Cited by 11 publications

References 59 publications

Plant-Based Bioactive Phthalates Derived fromHibiscus rosa-sinensis: As In Vitro and In Silico Enzyme Inhibition

Plant-Based Bioactive Phthalates Derived fromHibiscus rosa-sinensis: As In Vitro and In Silico Enzyme Inhibition

Identification of Phthalates, Methyl Esters and Siloxanes through GCMS analysis, biological investigation, DFT and Molecular Docking studies on Methanolic Subfractions of Hibiscus Rosa Sinensis flower extract

Evaluation of antibacterial, cytotoxicity, and apoptosis activity of novel chromene-sulfonamide hybrids synthesized under solvent-free conditions and 3D-QSAR modeling studies

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