N1-(3-(Trifluoromethyl)Phenyl) Isophthalamide Derivatives as Promising Inhibitors of Vascular Endothelial Growth Factor Receptor: Pharmacophore-Based Design, Docking, and MM-PBSA/MM-GBSA Binding Energy Estimation

Faryna, Aliaksandr; Kalinichenko, Еlena N.

doi:10.5772/intechopen.107236

Cited by 2 publications

(2 citation statements)

References 62 publications

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“… Binding models of 14 (left, PDB id: 3wze) and 11 (right, PDB id: 4asd) to VEGFR, predicted using molecular modeling. Hydrogen bonds are shown as orange lines [ 50 ]. …”

Section: Figures Scheme and Tablesmentioning

confidence: 99%

Novel Phthalic-Based Anticancer Tyrosine Kinase Inhibitors: Design, Synthesis and Biological Activity

Kalinichenko

Faryna

Bozhok

et al. 2023

CIMB

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In this work, fragments of isophthalic and terephthalic acids are proposed as a structural scaffold to develop potential inhibitors of protein kinases. Novel isophthalic and terephthalic acid derivatives were designed as type-2 protein kinase inhibitors, synthesized and subjected to physicochemical characterization. The screening of their cytotoxic actions against a panel of cell lines derived from different types of tumors (liver, renal, breast and lung carcinomas, as well as chronic myelogenous and promyelocytic leukemia) and normal human B lymphocyte, for the sake of comparison, was performed. Compound 5 showed the highest inhibitory activity against four cancer cell lines, K562, HL-60, MCF-7 and HepG2 (IC50 = 3.42, 7.04, 4.91 and 8.84 µM, respectively). Isophthalic derivative 9 revealed a high potency against EGFR and HER2, at the levels of 90% and 64%, respectively, being comparable to lapatinib at 10 µM. In general, tumor cell cultures were more sensitive to isophthalic acid derivatives than to terephthalic acid ones. In cell cycle studies, isophthalic analogue 5 showed a pronounced dose-dependent effect, and with the increase in its concentration up to 10.0 µM, the number of living cells decreased to 38.66%, while necrosis reached 16.38%. The considered isophthalic compounds had a similar docking performance to that of sorafenib against the VEGFR-2 (PDB id: 4asd, 3wze). The correct binding of compounds 11 and 14 with VEGFR-2 was validated using MD simulations and MM-GPSA calculations.

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“… Binding models of 14 (left, PDB id: 3wze) and 11 (right, PDB id: 4asd) to VEGFR, predicted using molecular modeling. Hydrogen bonds are shown as orange lines [ 50 ]. …”

Section: Figures Scheme and Tablesmentioning

confidence: 99%

Novel Phthalic-Based Anticancer Tyrosine Kinase Inhibitors: Design, Synthesis and Biological Activity

Kalinichenko

Faryna

Bozhok

et al. 2023

CIMB

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“…Apart from the technical implementation, the main difference between the two programs is that g_mmpbsa evaluates only the PBSA variant, whereas gmx_MMPBSA can be employed to evaluate both PBSA and GBSA variants. [70,71] Thus, the gmx_MMPBSA program was employed to evaluate the binding free energy (ΔG binding ) of boceprevir with M pro using MM-PBSA and MM-GBSA methods. The ΔG binding was reported to be relative binding free energy in which the contribution of conformational entropy was ignored during the evaluation of binding free energy as per previous computational studies.…”

Section: Simulation Setupmentioning

confidence: 99%

Insights into the Interaction Mechanism of Boceprevir with SARS‐CoV‐2 Main Protease

Kaur

Goyal

2023

ChemistrySelect

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The main protease (M pro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a prominent drug target as it plays a key role in viral replication and is greatly conserved in the coronaviruses with no homologues in the human genome. Ma et al. reported boceprevir, an FDA-approved hepatitis C virus (HCV) drug, for inhibiting SARS-CoV-2 M pro activity (IC 50 = 4.13 � 0.61 μM). However, how boceprevir inhibits M pro activity remains unexplored. The molecular dynamics (MD) simulations have been utilized in the present study to examine the mechanistic basis of the high-affinity binding of boceprevir with SARS-CoV-2 M pro . The molecular docking analysis depicted a strong binding (À 7.5 kcal/mol) of boceprevir to M pro due to its hydrogen bond interactions with catalytic dyad (Cys145) and oxyanion hole residues (Asn142, Gly143) of M pro . MD simulations revealed the structural stability of the M pro -boceprevir complex during the whole simulation. The MD simulations illuminated key interactions of boceprevir with the residues lining the subpockets of the active site of M pro , which is consistent with its high-affinity binding with M pro observed in the in vitro studies. The results from the current investigation will offer direction and valuable insights for developing novel M pro inhibitors.

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N1-(3-(Trifluoromethyl)Phenyl) Isophthalamide Derivatives as Promising Inhibitors of Vascular Endothelial Growth Factor Receptor: Pharmacophore-Based Design, Docking, and MM-PBSA/MM-GBSA Binding Energy Estimation

Cited by 2 publications

References 62 publications

Novel Phthalic-Based Anticancer Tyrosine Kinase Inhibitors: Design, Synthesis and Biological Activity

Novel Phthalic-Based Anticancer Tyrosine Kinase Inhibitors: Design, Synthesis and Biological Activity

Insights into the Interaction Mechanism of Boceprevir with SARS‐CoV‐2 Main Protease

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