Extensive Study of DFT-Quantum Calculations Based QSAR Modeling of Fused 1,2,4-Triazine Derivatives Revealed Potent CYP1A1 Inhibitors

Ahmed, Hany E. A.; Amer, Adel; Senior, Samir A.; Ihmaid, Saleh; Almalghrabi, Mohammad; Massry, Abdel-Moneim El; Ahmed, Sahar; Musa, Arafa; Almikhlafi, Mohannad A.; Salama, Samir A.; Elhenawy, Ahmed A.

doi:10.1142/s2737416522300036

Cited by 4 publications

(3 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The qualifications value for η exhibited a low aptitude transformation of electronic current to distortion direction. As expected [ 39 ], the anticancer efficiency for biomolecules renationalized directly with the antioxidant power, which was related to the small value of the ionization potential (IP) [ 38 ]. The molecule had scavenging ability due to the transfer one electron mechanism, and a healthier antioxidant [ 39 ].…”

Section: Resultsmentioning

confidence: 62%

See 1 more Smart Citation

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

et al. 2023

Self Cite

View full text Add to dashboard Cite

5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine (1). The reaction of the latter compound (1) with a series of halogenated derivatives under conditions of phase transfer catalysis solid–liquid (CTP) allows the isolation of the expected regioisomers compounds (2–8). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data (1H NMR, 13C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4, were tested in vitro for their antibacterial activity against Gram-positive bacteria (Bacillus cereus) and Gram-negative bacteria (Escherichia coli). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

show abstract

Section: Resultsmentioning

confidence: 62%

“…105 to 0.177 au. for 6-bromo-2-phenyl-3H-imidazo[4,5-b]pyridine hybrids 1 – 8 and the reported biomaterials values were harmonized [ 38 ]. HOMO was distributed in 1 – 8 over the phenyl-3H-imidazo[4,5-b]pyridine fragment.…”

Section: Resultsmentioning

confidence: 99%

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…QZ59-RRR which is the reference inhibitor in the crystal P -gp macromolecule was docked with high precision into the experimentally obtained mouse P -gp structure and resulted in an RMSD value of 1.78 Å, these results imply that the docking analysis was precise and trustworthy. The binding free energies ΔG obtained from the redocking experiment utilizing Glide's module® 63 , 64 are shown in (Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and bioactivity study on oxygen-heterocyclic-based pyran analogues as effective P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cell

Abd El-Wahab,

Borik,

Al-Dies

et al. 2024

Sci Rep

Self Cite

View full text Add to dashboard Cite

P-glycoprotein (P-gp) imparts multi-drug resistance (MDR) on the cancers cell and malignant tumor clinical therapeutics. We report a class of newly designed and synthesized oxygen-heterocyclic-based pyran analogues (4a–l) bearing different aryl/hetaryl-substituted at the 1-postion were synthesized, aiming to impede the P-gp function. These compounds (4a–l) have been tested against cancerous PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines as well as non-cancerous HFL-1 and WI-38 cell lines to determine their anti-proliferative potency.The findings demonstrated the superior potency of 4a–c with 4-F, 2-Cl, and 3-Cl derivatives and 4h,g with 4-NO2, 4-MeO derivatives against PC-3, SKOV-3, HeLa, and MCF-7/ADR cell lines.Compounds 4a–c were tested for P-gp inhibition and demonstrated significant vigour against MCF-7/ADR cells with IC50 = 5.0–10.7 μM. The Rho123 accumulation assay showed that compounds 4a–c adequately inhibited P-gp function, as predicted. Furthermore, 4a or 4b administration resulted in MCF-7/ADR cell accumulation in the S phase, while compound 4c induced apoptosis by causing cell cycle arrest at G2/M. The molecular docking was applied to understand the likely modes of action and guide us in the rational design of more potent analogs. The investigate derivatives showed their good binding potential for p-gp active site with excellent docking scores and interactions. Finally, the majority of investigated derivatives 4a–c derivatives showed high oral bioavailability, but they did not cross the blood–brain barrier. These results suggest that they have favorable pharmacokinetic properties. Therefore, these compounds could serve as leads for designing more potent and stable drugs in the future.

show abstract

N- and s-substituted Pyrazolopyrimidines: A promising new class of potent c-Src kinase inhibitors with prominent antitumor activity

Awaji,

Zaloa,

Seleem

et al. 2024

Bioorganic Chemistry

View full text Add to dashboard Cite

Extensive Study of DFT-Quantum Calculations Based QSAR Modeling of Fused 1,2,4-Triazine Derivatives Revealed Potent CYP1A1 Inhibitors

Cited by 4 publications

References 47 publications

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

Exploring Antimicrobial Features for New Imidazo[4,5-b]pyridine Derivatives Based on Experimental and Theoretical Study

Design, synthesis and bioactivity study on oxygen-heterocyclic-based pyran analogues as effective P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cell

N- and s-substituted Pyrazolopyrimidines: A promising new class of potent c-Src kinase inhibitors with prominent antitumor activity

Contact Info

Product

Resources

About