Pyrazolo-imidazolidinones: Synthesis, antimicrobial assessment and molecular modelling studies by molecular mechanic and quantum mechanic approach

Desai, N. C.; Joshi, Surbhi B.; Khasiya, Ashvinkumar G.; Jadeja, Dharmpalsinh J.; Mehta, Harsh K.; Pandya, Medha; Ahmad, Iqrar; Patel, Harun

doi:10.1016/j.molstruc.2022.134000

Cited by 17 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By docking poses, the lead molecule ISB1, in the hMAO-B enzyme with the least negative score (e.g., the top-docking poses), was the subject of molecular dynamics (MD) research utilizing Desmond in NVIDIA Quadro 6000 graphics processing unit. [71][72][73] In order to construct trajectories of 1000 frames each to explore interactions between protein and ligand, the default parameter was employed for the systems under research. This included 100 ns MD generation with coordinates recorded at 100 ps.…”

Section: Molecular Dynamic (Md) Simulationmentioning

confidence: 99%

Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment

Benny,

Oh,

Kumar

et al. 2023

RSC Adv.

View full text Add to dashboard Cite

show abstract

Section: Molecular Dynamic (Md) Simulationmentioning

confidence: 99%

Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment

Benny,

Oh,

Kumar

et al. 2023

RSC Adv.

View full text Add to dashboard Cite

show abstract

“…Molecular dynamics (MD) studies were carried out utilizing an NVIDIA Quadro 6000 graphics processing unit and the Desmond MD simulation software for the docking poses of CA4 in the hMAO-B enzyme with the lowest negative score, i.e., top-docking poses. − As earlier studies, more information for MD investigations such as thermostat and barometer settings, box type, short- and long-range interaction calculations was considered because the same settings were applied for the analyzed systems here, i.e., 100 ns of MD generation was done, with coordinates stored at 100 ps to produce trajectories of 1000 frames each for investigating the dynamics of protein–ligand interactions. − Finally, the simulated interaction diagram tool was used for stability analysis.…”

Section: Methodsmentioning

confidence: 99%

Development of Isopropyl-Tailed Chalcones as a New Class of Selective MAO-B Inhibitors for the Treatment of Parkinson’s Disorder

Abdelgawad

Abourehab

et al. 2023

ACS Omega

Self Cite

View full text Add to dashboard Cite

Thirteen isopropyl chalcones (CA1−CA13) were synthesized and evaluated for their inhibitory activity against monoamine oxidase (MAO). All compounds inhibited MAO-B more effectively than MAO-A. Compound CA4 most potently inhibited MAO-B with an IC 50 value of 0.032 μM, similar to that of CA3 (IC 50 = 0.035 μM) and with high selectivity index (SI) values for MAO-B over respectively). The −OH (CA4) or −F (CA3) group at the para position on the A ring provided higher MAO-B inhibition than that of the other substituents (−OH ≥ −F > −Cl > −Br > −OCH 2 CH 3 > −CF 3 ). On the other hand, compound CA10 most potently inhibited MAO-A with an IC 50 value of 0.310 μM and effectively MAO-B (IC 50 = 0.074 μM). The Br-containing thiophene substituent (CA10) instead of the A ring showed the highest MAO-A inhibition. In a kinetic study, K i values of compounds CA3 and CA4 for MAO-B were 0.076 ± 0.001 and 0.027 ± 0.002 μM, respectively, and that of CA10 for MAO-A was 0.016 ± 0.005 μM. A reversibility study showed that CA3 and CA4 were reversible inhibitors of MAO-B and CA10 was a reversible inhibitor of MAO-A. In docking and molecular dynamics, the hydroxyl group of CA4 and two hydrogen bonds contributed to the stability of the protein−ligand complex. These results suggest that CA3 and CA4 are potent reversible selective MAO-B inhibitors and can be used for the treatment of Parkinson's disease.

show abstract

“…The study was performed using Schrödinger Glide. The ligand, protein, grid file, and docking approach were all carried out in accordance with our earlier study [ 45 , 46 , 47 ].…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Silico Evaluation of Antiproliferative Activity of New Isoxazolidine Derivatives Targeting EGFR: Design, Synthesis, Cell Cycle Analysis, and Apoptotic Inducers

Alminderej,

Ghannay,

Elsamani

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

A series of novel enantiopure isoxazolidine derivatives were synthesized and evaluated for their anticancer activities against three human cancer cell lines such as human breast carcinoma (MCF-7), human lung adenocarcinoma (A-549), and human ovarian carcinoma (SKOV3) by employing MTT assay. The synthesized compounds were characterized by NMR and elemental analysis. Results revealed that all the synthesized compounds displayed significant inhibition towards the tested cell lines. Among them, 2g and 2f, which differ only by the presence of an ester group at the C-3 position and small EDG (methyl) at the C-5 position of the phenyl ring (2g), were the most active derivatives in attenuating the growth of the three cells in a dose-dependent manner. The IC50 for 2g were 17.7 ± 1 µM (MCF-7), 12.1 ± 1.1 µM (A-549), and 13.9 ± 0.7 µM (SKOV3), and for 2f were 9.7 ± 1.3µM (MCF-7), 9.7 ± 0.7µM (A-549), and 6.5 ± 0.9µM (SKOV3), respectively, which were comparable to the standard drug, doxorubicin. The enzymatic inhibition of 2f and 2g against EGFR afforded good inhibitory activity with IC50 of 0.298 ± 0.007 μM and 0.484 ± 0.01 µM, respectively, close to the positive control, Afatinib. Compound 2f arrested the cell cycle in the S phase in MCF-7 and SKOV3 cells, and in the G2/M phase in the A549 cell; however, 2g induced G0/G1 phase cell cycle arrest, and inhibited the progression of the three cancer cells, together with significant apoptotic effects. The docking study of compounds 2f and 2g into EGFR ATP-active site revealed that it fits nicely with good binding affinity. The pharmacokinetic and drug-likeness scores revealed notable lead-like properties. At 100 ns, the dynamic simulation investigation revealed high conformational stability in the EGFR binding cavity.

show abstract

Pyrazolo-imidazolidinones: Synthesis, antimicrobial assessment and molecular modelling studies by molecular mechanic and quantum mechanic approach

Cited by 17 publications

References 38 publications

Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment

Isatin-based benzyloxybenzene derivatives as monoamine oxidase inhibitors with neuroprotective effect targeting neurogenerative disease treatment

Development of Isopropyl-Tailed Chalcones as a New Class of Selective MAO-B Inhibitors for the Treatment of Parkinson’s Disorder

In Vitro and In Silico Evaluation of Antiproliferative Activity of New Isoxazolidine Derivatives Targeting EGFR: Design, Synthesis, Cell Cycle Analysis, and Apoptotic Inducers

Contact Info

Product

Resources

About