<i>In vitro</i> biological studies and computational prediction-based analyses of pyrazolo[1,5-<i>a</i>]pyrimidine derivatives

Almehizia, Abdulrahman A.; Aboulthana, Wael M.; Naglah, Ahmed M.; Hassan, Ashraf S.

doi:10.1039/d4ra00423j

Cited by 5 publications

(1 citation statement)

References 106 publications

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“…Additionally, Almehizia and his colleagues' research indicated that pyrazolo [1, 5-a]pyrimidine derivatives possess various biological activities against cancer, diabetes, Alzheimer's disease, and inflammation. Therefore, they were suggested as multi-target agents [8].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer’s, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions

Naglah,

Almehizia,

Al-Wasidi

et al. 2024

Pharmaceuticals

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In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. In this context, we re-synthesized three sets of pyrazole-based Schiff bases, 5a–f, 6a–f, and 7a–f, to evaluate their biological applications. The data from in vitro biological assays (including antioxidant and scavenging activities, anti-diabetes, anti-Alzheimer’s, and anti-inflammatory properties) of the pyrazole-based Schiff bases 5a–f, 6a–f, and 7a–f showed that the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f possess the highest biological properties among the compounds evaluated. The cytotoxicity against lung (A549) and colon (Caco-2) human cancer types, as well as normal lung (WI-38) cell lines, was evaluated. The data from the cytotoxicity investigation demonstrated that the three Schiff bases 5d, 5e, and 7a are active against lung (A549) cells, while the two Schiff bases 5e and 7a exhibited the highest cytotoxicity towards colon (Caco-2) cells. Additionally, the enzymatic activities against caspase-3 and Bcl-2 of the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f were evaluated. Furthermore, we assessed the in silico absorption, distribution, metabolism, and toxicity (ADMT) properties of the more potent pyrazole-based Schiff bases. After modifying the structures of the six pyrazole-based Schiff bases, we plan to further extend the studies in the future.

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Section: Introductionmentioning

confidence: 99%

Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer’s, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions

Naglah,

Almehizia,

Al-Wasidi

et al. 2024

Pharmaceuticals

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Explore new quinoxaline pharmacophore tethered sulfonamide fragments as in vitro α‐glucosidase, α‐amylase, and acetylcholinesterase inhibitors with ADMET and molecular modeling simulation

Ragab,

Salem,

Ammar

et al. 2024

Drug Development Research

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A new series of quinoxaline‐sulfonamide derivatives 3–12 were synthesized using fragment‐based drug design by reaction of quinoxaline sulfonyl chloride (QSC) with different amines and hydrazines. The quinoxaline‐sulfonamide derivatives were evaluated for antidiabetic and anti‐Alzheimer's potential against α‐glucosidase, α‐amylase, and acetylcholinesterase enzymes. These derivatives showed good to moderate potency against α‐amylase and α‐glucosidase with inhibitory percentages between 24.34 ± 0.01%–63.09 ± 0.02% and 28.95 ± 0.04%–75.36 ± 0.01%, respectively. Surprisingly, bis‐sulfonamide quinoxaline derivative 4 revealed the most potent activity with inhibitory percentages of 75.36 ± 0.01% and 63.09 ± 0.02% against α‐glucosidase and α‐amylase compared to acarbose (IP = 57.79 ± 0.01% and 67.33 ± 0.01%), respectively. Moreover, the quinoxaline derivative 3 exhibited potency as α‐glucosidase and α‐amylase inhibitory with a minute decline from compound 4 and acarbose with inhibitory percentages of 44.93 ± 0.01% and 38.95 ± 0.01%. Additionally, in vitro acetylcholinesterase inhibitory activity for designed derivatives exhibited weak to moderate activity. Still, sulfonamide‐quinoxaline derivative 3 emerged as the most active member with inhibitory percentage of 41.92 ± 0.02% compared with donepezil (IP = 67.27 ± 0.60%). The DFT calculations, docking simulation, target prediction, and ADMET analysis were performed and discussed in detail.

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Synthesis, structural, molecular docking, and in vitro biological activities of Cu-doped ZnO nanomaterials

El-Sayed,

Aboulthana,

Sherief

et al. 2024

Sci Rep

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Copper-doped ZnO nanoparticles with the formula Zn1−x(Cu)O, where x = 0.0, 0.03, 0.05, and 0.07 were produced using the co-precipitation process. Physical, chemical, and structural properties were properly examined. Powdered X-ray diffraction (P-XRD) patterns revealed the formation of hexagonal wurtzite crystal structure in all samples, through atomic substitutional incorporation in the Cu-doped ZnO lattice. The presence of Cu ions and their dissolution in the host ZnO crystal structure was supported by FT-IR spectra. HR-TEM images were used to assess the average size, morphology, and shape regularity of the synthesized samples. The form and homogeneity of the ZnO changed when Cu ions were substituted, as evidenced by FE-SEM/EDX analysis. The presence of copper signals in the Cu-doped samples indicates that the doping was successful. The decrease in zeta potential with an increased copper doping percentage designates that the nanoparticles (NPs) are more stable, which could be attributed to an increase in the ionic strength of the aqueous solution. The synthesized NPs were evaluated for their substantial in vitro antioxidant properties. In addition, the antimicrobial efficacy of the materials was tested against pathogenic microorganisms. Regarding the anti-diabetic activity, the 7Cu ZnO sample showed the highest inhibitory effect on the α-amylase enzyme. No variations were observed in the activities of the acetylcholinesterase enzyme (AChE) and proteinase enzymes with ZnO and samples doped with different concentrations of Cu. Therefore, further studies are recommended to reveal the in-vitro anti-diabetic activity of the studied doped samples. Finally, molecular docking provided valuable insights into the potential binding interactions of Cu-doped ZnO with α-amylase, FabH of E. coli, and Penicillin-binding proteins of S. aureus. These outcomes suggest that the prepared materials may have an inhibitory effect on enzymes and hold promise in the battle against microbial infections and diabetes.

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In vitro biological studies and computational prediction-based analyses of pyrazolo[1,5-a]pyrimidine derivatives

Abstract: Recently, new pharmaceutical discoveries have become very important for addressing diverse health problems and protecting humanity.

Cited by 5 publications

References 106 publications

Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer’s, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions

Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer’s, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions

Explore new quinoxaline pharmacophore tethered sulfonamide fragments as in vitro α‐glucosidase, α‐amylase, and acetylcholinesterase inhibitors with ADMET and molecular modeling simulation

Synthesis, structural, molecular docking, and in vitro biological activities of Cu-doped ZnO nanomaterials

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