Molecular engineering of complexation between RNA and biodegradable cationic gemini surfactants: role of the hydrophobic chain length

Akram, Mohd.; Lal, Hira; Shakya, Sonam; Varshney, Rohit Kumar; Uddin, Kabir M.

doi:10.1039/d1me00147g

Cited by 27 publications

(7 citation statements)

References 85 publications

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“…Chemoinformatics (in silico techniques) was used as an efficient approach in drug discovery with the advantage of saving time, effort, and costs [11][12][13]. This includes molecular docking [14,15], ADMET assessment [15] and MD simulation techniques [14,16].…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway

et al. 2022

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We report herein, the design and synthesis of thiazolidine-2,4-diones derivatives as new inhibitors for VEGFR-2. The designed members were assessed for their in vitro anticancer activity against four cancer cell lines; A549, Caco-2, HepG-2 and MDA-MB-231. Compound 14a showed the most potent effects against Caco-2, and HepG-2 cell lines (IC50 = of 1.5 and 31.5 μM, respectively). Next, the in vitro VEGFR-2 inhibitory activity, safety profiles and selectivity indices were examined for all the synthesized members against the normal Vero cell line. Compound 14a (the safest member against Caco-2 cell line) was further investigated for its ability to inhibit Caco-2 cells migration and healing. Moreover, the apoptotic induction of compound 14a against Caco-2 cell line was investigated by assessing against four apoptotic genes (Bcl2, Bcl-xl, TGF, and Survivin). The results revealed that compound 14a can exert apoptosis through significant reduction of Bcl2, Survivin, and TGF gene expression levels. Finally, deep computational studies including molecular docking, ADMET, toxicity studies, and MD simulation were carried out. Also, the DFT calculations were performed and discussed, and the results confirmed the inhibitory reactivity of 14a against VEGFR-2. Compound 14a is expected to be used as a potential lead in the development of new VEGFR-2 inhibitors with increased potency.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway

et al. 2022

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“…Furthermore, the simulated docking of the active backbone with the active site in the crystal complex of EGFR and c-Met proteins, respectively, was carried out. Finally, a 3D-QSAR model was constructed for molecular simulation calculation and scoring [ 30 , 31 , 32 ]. Finally, potential multi-target inhibitors based on EGFR and c-Met were screened out.…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Multi-Target Anti-Cancer Agent PYR26

et al. 2023

IJMS

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This study investigates the synthesis of a new compound, PYR26, and the multi-target mechanism of PYR26 inhibiting the proliferation of HepG2 human hepatocellular carcinoma cells. PYR26 significantly inhibits the growth of HepG2 cells (p < 0.0001) and this inhibition has a concentration effect. There was no significant change in ROS release from HepG2 cells after PYR26 treatment. The mRNA expressions of CDK4, c-Met and Bak genes in HepG2 cells were significantly inhibited (p < 0.05), while mRNA expression of pro-apoptotic factors such as caspase-3 and Cyt c was significantly increased (p < 0.01). The expression of PI3K, CDK4 and pERK proteins decreased. The expression level of caspase-3 protein was increased. PI3K is a kind of intracellular phosphatidylinositol kinase. PI3K signaling pathway is involved in signal transduction of a variety of growth factors, cytokines and extracellular matrix and plays an important role in preventing cell apoptosis, promoting cell survival and influencing cell glucose metabolism. CDK4 is a catalytic subunit of the protein kinase complex and is important for G1 phase progression of the cell cycle. PERK refers to phosphorylated activated ERK, which is translocated from cytoplasm to the nucleus after activation, and then participates in various biological reactions such as cell proliferation and differentiation, cell morphology maintenance, cytoskeleton construction, cell apoptosis and cell canceration. Compared with the model group and the positive control group, the tumor volume of the nude mice in the low-concentration PYR26 group, the medium-concentration group and the high-concentration group was smaller, and the organ volume was smaller than that in the model group and the positive control group. The tumor inhibition rates of low-concentration group PYR26, medium-concentration group and high-concentration group reached 50.46%, 80.66% and 74.59%, respectively. The results showed that PYR26 inhibited the proliferation of HepG2 cells and induced apoptosis of HepG2 cells by down-regulating c-Met, CDK4 and Bak, up-regulating the mRNA expression of caspase-3 and Cyt c genes, down-regulating PI3K, pERK and CDK4 proteins and up-regulating the protein level of caspase-3. In a certain range, with the increase in PYR26 concentration, the tumor growth was slower and the tumor volume was smaller. Preliminary results showed that PYR26 also had an inhibitory effect on the tumors of Hepa1-6 tumor-bearing mice. These results suggest that PYR26 has an inhibitory effect on the growth of liver cancer cells, therefore it has potential to be developed into a new anti-liver cancer drug.

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“…The application of molecular simulation docking technology is a crucial approach for investigating the interaction between drugs and proteins. [21,22] The binding sites and primary binding forces of CHL and PEP were investigated using molecular simulation docking technology. DS2016Client and AutoDock 4.2.6 were utilized for the docking of CHL and PEP, and the combined conformation results with the lowest free energy are presented in Figure 6.…”

Section: Molecular Docking Simulationmentioning

confidence: 99%

Effect of Chloramphenicol as Antibiotic on the Structure and Function of Pepsin and Its Mechanism of Action

Wang,

Sun,

Nie

et al. 2023

Chemistry & Biodiversity

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The interaction between chloramphenicol (CHL) and pepsin (PEP), as well as the impact of CHL on PEP conformation, were investigated using spectroscopic techniques and molecular docking simulations in this study. The experimental results demonstrate that CHL exhibits a static quenching effect on PEP. The thermodynamic parameters indicate that the reaction between CHL and PEP is spontaneous, primarily driven by hydrogen bonding and van der Waals forces. Moreover, the binding distance of r<7 nm suggests the occurrence of Förster's non‐radiative energy transfer between these two molecules. In the synchronous fluorescence spectrum, the maximum fluorescence intensity of PEP produced a redshift phenomenon, indicating that CHL was bound to tryptophan residues of PEP. The addition of CHL induces changes in the secondary structure of PEP, as confirmed by the observed alterations in peak values in three‐dimensional fluorescence spectra. The UV spectra reveal a redshift of 3 nm in the maximum absorption peak, indicating a conformational change in the secondary structure of PEP upon addition of CHL. Circular dichroism analysis demonstrates significant alterations in the α‐helix, β‐sheet, β‐turn, and random coil contents of PEP before and after CHL incorporation, further confirming its ability to modulate the secondary structure of PEP.

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Molecular engineering of complexation between RNA and biodegradable cationic gemini surfactants: role of the hydrophobic chain length

Abstract: Transfection efficiency of material into cells is directly related to the success rate of gene therapy. The synthetic lipid-like molecules, comparable with components of biological membranes, can offer the golden...

Cited by 27 publications

References 85 publications

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway

Design, Synthesis and Biological Evaluation of Multi-Target Anti-Cancer Agent PYR26

Effect of Chloramphenicol as Antibiotic on the Structure and Function of Pepsin and Its Mechanism of Action

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