Isoquinolinedione-urea hybrids: Synthesis, antibacterial evaluation, drug-likeness, molecular docking and DFT studies

Han, M. İhsan; Dengiz, Çağatay; Doğan, Şengül Dilem; Gündüz, Miyase Gözde; Köprü, Semiha; Özkul, Ceren

doi:10.1016/j.molstruc.2021.132007

Cited by 9 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The DFT computation revealed that 4b had the highest global hardness value as expected. This study implicated that 4b might be the most stable as well the least reactive (Han et al, 2022).…”

Section: Dft Studiesmentioning

confidence: 68%

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

Saeed,

Shahzadi,

Zahoor

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%–95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (−7.55 kcal/mol) with the active site of serine protease, better than compound 4c (−6.90 kcal/mol) as well as indole-based control compound 5 (−7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 μg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 μg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 μg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 μg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development.

show abstract

Section: Dft Studiesmentioning

confidence: 68%

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

Saeed,

Shahzadi,

Zahoor

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

show abstract

“…This strategy is based on the concept that chemical stability is linked to the processes of electron transfer. To be more precise, during chemical reactions, electrons are initially taken from the HOMO and transferred to the LUMO of the reacting substances …”

Section: Resultsmentioning

confidence: 99%

“…To be more precise, during chemical reactions, electrons are initially taken from the HOMO and transferred to the LUMO of the reacting substances. 39 …”

Section: Resultsmentioning

confidence: 99%

Palladium Metal Nanocomposites Based on PEI-Functionalized Nitrogen-Doped Graphene Quantum Dots: Synthesis, Characterization, Density Functional Theory Modeling, and Cell Cycle Arrest Effects on Human Ovarian Cancer Cells

Gunes,

Kirlangic,

Kilic

et al. 2024

ACS Omega

View full text Add to dashboard Cite

In this study, the synthesis, characterization, density functional theory calculations (DFT), and effect of polyethylenimine (PEI)-functionalized nitrogen-doped graphene quantum dots (PEI N-GQDs) and their palladium metal nanoparticles nanocomposites (PdNPs/PEI N-GQDs) on cancer cells were extensively investigated. The focus also includes investigating their cytotoxic and apoptotic effects on ovarian cancer cells, which pose a serious risk to women’s health and have high death rates from delayed diagnosis, inadequate response to treatment, and decreased survival. Graphene quantum dots and their palladium nanocomposites were differentially effective against ovarian cancer cell lines. In particular, the smaller particle size and morphology of PdNPs/PEI N-GQDs nanocomposites compared with PEI N-GQDs probably enhance their activity through highly improved uptake by cells. These findings emphasize the importance of particle size in composite drugs for efficient cancer treatment. DFT results revealed that the Pd-containing nanocomposite, with a smaller highest occupied molecular orbital–lowest unoccupied molecular orbital gap, exhibited higher reactivity and anticancer effects in human ovarian cancer cell line, OVCAR-3. Significantly, the application of nanocomposites to ovarian cancer cells initiated apoptosis, offering valuable insights into the intricate interplay between nanomaterials and cancer biology.

show abstract

“…Then, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), and related calculations were done. The DFT computation outputs were analyzed by using GaussView 5.0 [74] …”

Section: Methodsmentioning

confidence: 99%

Synthesis, DFT Calculations, and Molecular Docking Study of Acetohydrazide‐Based Sulfonamide Derivatives as Paraoxonase 1 Inhibitors

Arslan¹,

Gökçe²,

Muhammed³

et al. 2023

ChemistrySelect

View full text Add to dashboard Cite

Paraoxonase 1 (PON1), an esterase linked to high-density lipoprotein (HDL), is known to have strong antioxidant and anti-cardiovascular properties. In this study, eleven acetohydrazide-based sulfonamide derivatives were synthesized. All compounds were characterized by appropriate spectroscopic techniques and elemental analyses. To better understand the inhibitory properties of the new sulfonamide derivatives, their in vitro effects on purified PON1 enzyme activity were studied. For this purpose, PON1 was purified from human serum using simple chromatographic methods. In the experimental study, the novel compounds were found to be potent inhibitors of paraoxonase 1. The mode of binding to the enzyme, for the relatively active compounds, was investigated through molecular docking. The most active compound N'-(naphthalen-2ylsulfonyl)-2-(2-oxo-1,3-benzothiazol-3(2H)-yl)acetohydrazide demonstrated the highest interaction with the enzyme. Furthermore, the electrochemical properties of these compounds were assessed through DFT (density functional theory) analysis. N'-(naphthalen-2-ylsulfonyl)-2-(2-oxo-1,3-benzothiazol-3(2H)-yl)acetohydrazide is anticipated to have the highest potential to take part in electron exchanges whereas N'-[(4fluorophenyl)sulfonyl]-2-(2-oxo-1,3-benzoxazol-3(2H)yl)acetohydrazide is expected to have the highest chemical stability.

show abstract

Isoquinolinedione-urea hybrids: Synthesis, antibacterial evaluation, drug-likeness, molecular docking and DFT studies

Cited by 9 publications

References 44 publications

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

Palladium Metal Nanocomposites Based on PEI-Functionalized Nitrogen-Doped Graphene Quantum Dots: Synthesis, Characterization, Density Functional Theory Modeling, and Cell Cycle Arrest Effects on Human Ovarian Cancer Cells

Synthesis, DFT Calculations, and Molecular Docking Study of Acetohydrazide‐Based Sulfonamide Derivatives as Paraoxonase 1 Inhibitors

Contact Info

Product

Resources

About