New Pyridopyrimidone Derivatives: Synthesis,Molecular Docking Studies,and Potential Anticancer Activity

Russian Journal of General Chemistry - A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesized and tested in vitro for cytotoxic effect against cancer...     

Optimization Method for Phenolic Compounds Extraction from Medicinal Plant (Juniperus procera) and Phytochemicals Screening

Juniperus procera is a natural source of bioactive compounds with the potential of antitumor, antimicrobial, insecticidal, antifungal, and antioxidant activities. An optimization method was developed for total phenolic content (TPC), total flavonoid content (TFC), and total tannin content (TTC) in leaf and seed extract of Juniperus procera. Organic solvents (methanol (99.8%), ethanol (99%), and acetone (99.5%)), and deionized water (DI) were used for extraction. The estimation of TPC, TFC, and TTC in plant materials was carried out using UV-spectrophotometer and HPLC with the standards gallic acid, quercetin, and tannic acid. Recovery of TPC in leaf extract ranged from 2.9 to 9.7 mg GAE/g DW, TFC from 0.9 to 5.9 mg QE/g DW, and TTC ranged from 1.5 to 4.3 mg TA/g DW while the TPC value in the seed extract ranged from 0.53 to 2.6 mg GAE/g DW, TFC from 0.5 to 1.6 mg QE/g DW, and TTC ranged from 0.5 to 1.4 mg TA/g DW. This result revealed that methanol is the best solvent for recovery of the TPC value (9.7 mg) from leaf extract in comparison to other solvents. Ethanol recorded the highest result of TFC (5.9 mg) in leaf extract among the solvents whereas acetone was the best for TTC yield recovery from leaf extract (4.3 mg). In the case of the seed extract, ethanol was the best solvent for both TPC (2.6 mg), and TFC (1.6 mg) recovery in comparison to other solvents. Total tannin content in methanol resulted in significant recovery from seed extract (1.4 mg). Separation and quantification of gallic acid, quercetin, and tannic acid in plant materials were undertaken using HPLC. Gallic acid in leaf and seed of J. procera ranged from 6.6 to 9.2, 6.5 to 7.2 µg/g DW, quercetin from 6.3 to 18.2, 0.9 to 4.2 µg/g DW, and tannic acid from 16.2 to 29.3, 6.6 to 9.3 µg/g DW, respectively. Solvents have shown a significant effect in the extraction of phenolic compounds. Moreover, phytochemicals in plant materials were identified using GC-MS and resulted in very important bioactive compounds, which include anti-inflammatory, antibacterial, and antitumor agents such as ferruginol, phenanthrene, and n-hexadecanoic acid. In conclusion, the optimal solvent for extraction depends on the part of the plant material and the compounds that are to be isolated.     

Investigations on Anticancer Potentials by DNA Binding and Cytotoxicity Studies for Newly Synthesized and Characterized Imidazolidine and Thiazolidine-Based Isatin Derivatives

Imidazolidine and thiazolidine-based isatin derivatives (IST-01–04) were synthesized, characterized, and tested for their interactions with ds-DNA. Theoretical and experimental findings showed good compatibility and indicated compound–DNA binding by mixed mode of interactions. The evaluated binding parameters, i.e., binding constant (K_b), free energy change (ΔG), and binding site sizes (n), inferred comparatively greater and more spontaneous binding interactions of IST-02 and then IST-04 with the DNA, among all compounds tested under physiological pH and temperature (7.4, 37 °C). The cytotoxic activity of all compounds was assessed against HeLa (cervical carcinoma), MCF-7 (breast carcinoma), and HuH-7 (liver carcinoma), as well as normal HEK-293 (human embryonic kidney) cell lines. Among all compounds, IST-02 and 04 were found to be cytotoxic against HuH-7 cell lines with percentage cell toxicity of 75% and 66%, respectively, at 500 ng/µL dosage. Moreover, HEK-293 cells exhibit tolerance to the increasing drug concentration, suggesting these two compounds are less cytotoxic against normal cell lines compared to cancer cell lines. Hence, both DNA binding and cytotoxicity studies proved imidazolidine (IST-02) and thiazolidine (IST-04)-based isatin derivatives as potent anticancer drug candidates among which imidazolidine (IST-02) is comparatively the more promising.     

Synthesis of New Naphthyl Aceto Hydrazone-Based Metal Complexes: Micellar Interactions,DNA Binding,Antimicrobial, and Cancer Inhibition Studies

In the present study, naphthyl acetohydrazide (HL) ligand was prepared and used for the synthesis of new six amorphous transition metal (Co(II), Ni(II), Cu(II), Zn(II), Pb(II), Cd(II)) complexes. All the compounds were characterized by elemental analysis, UV-vis, FT-IR, ¹H- and ¹³C-NMR, and Matrix-Assisted Laser Desorption Ionization (MALDI). The solubilization study was carried out by estimating the interaction between the metal complexes with surfactants viz. sodium stearate (SS) and Cetyltrimethylammonium bromide (CTAB). UV-Visible spectroscopy was employed to determine partitioning and binding parameters, whereas electrical conductivity measurements were employed to estimate critical micellar concentration (CMC), the extent of dissociation, and free energy of micellization. The CT-DNA interaction of synthesized compounds with DNA represents the major groove binding. The synthesized ligand and metal complexes were also tested against bacterial and fungal strains and it has been observed that Cu(II) complex is active against all the strains except Candida albicans, while Cd(II) complex is active against all bacterial and fungal strains except Pseudomonas. Among all compounds, only the Pd(II) complex shows reasonable activity against cervical cancer HeLa cell lines, representing 97% inhibition.     

Co-Inhibition of P-gp and Hsp90 by an Isatin-Derived Compound Contributes to the Increase of the Chemosensitivity of MCF7/ADR-Resistant Cells to Doxorubicin

Breast cancer is a complex and multi-drug resistant (MDR) disease, which could result in the failure of many chemotherapeutic clinical agents. Discovering effective molecules from natural products or by derivatization from known compounds is the interest of many research studies. The first objective of the present study is to investigate the cytotoxic combinatorial, chemosensitizing, and apoptotic effects of an isatin derived compound (5,5-diphenylimidazolidine-2,4-dione conjugated with 5-substituted isatin, named HAA₂₀₂₁ in the present study) against breast cancer cells (MCF7) and breast cancer cells resistant to doxorubicin (MCF7/ADR) when combined with doxorubicin. The second objective is to investigate the binding mode of HAA₂₀₂₁ withP-glycoprotein (P-gp) and heat shock protein 90 (Hsp90), and to determine whether their co-inhibition by HAA₂₀₂₁ contribute to the increase of the chemosensitization of MCF7/ADR cells to doxorubicin. The combination of HAA₂₀₂₁, at non-toxic doses, with doxorubicin synergistically inhibited the proliferation while inducing significant apoptosis in MCF7 cells. Moreover, HAA₂₀₂₁ increased the chemosensitization of MCF7/ADR cells to doxorubicin, resulting in increased cytotoxicity/selectivity and apoptosis-inducing efficiency compared with the effect of doxorubicin or HAA₂₀₂₁ alone against MCF7/ADR cells. Molecular modeling showed that two molecules of HAA₂₀₂₁ bind to P-gp at the same time, causing P-gp inhibitory effect of the MDR efflux pump, and accumulation of Rhodamine-123 (Rho123) in MCF7/ADR cells. Furthermore, HAA₂₀₂₁ stably interacted with Hsp90α more efficiently compared with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), which was confirmed with the surface plasmon resonance (SPR) and molecular modeling studies. Additionally, HAA₂₀₂₁ showed multi-target effects via the inhibition of Hsp90 and nuclear factor kappa B (NF-𝜅B) proteins in MCF7 and MCF7/ADR cells. Results of real time-PCR also confirmed the synergistic co-inhibition of P-gp/Hsp90α genes in MCF7/ADR cells. Further pharmacokinetic and in vivo studies are warranted for HAA₂₀₂₁ to confirm its anticancer capabilities.     

Efficacy of Precocene I from Desmosstachya bipinnata as an Effective Bioactive Molecules against the Spodoptera litura Fab. and Its Impact on Eisenia fetida Savigny

The sustainability of agroecosystems are maintained with agro-chemicals. However, after more than 80 years of intensive use, many pests and pathogens have developed resistance to the currently used chemistries. Thus, we explored the isolation and bioactivity of a chemical compound, Precocene I, isolated from the perennial grass, Desmosstachya bipinnata (L.) Stapf. Fractions produced from chloroform extractions showed suppressive activity on larvae of Spodoptera litura (Lepidoptera: Noctuidae), the Oriental armyworm. Column chromatography analyses identified Precocene I confirmed using FTIR, HPLC and NMR techniques. The bioactivity of the plant-extracted Dp-Precocene I was compared to a commercially produced Precocene I standard. The percentage of mortality observed in insects fed on plant tissue treated with 60 ppm Db-Precocene I was 97, 87 and 81, respectively, for the second, third and fourth instar larvae. The LC₅₀ value of third instars was 23.2 ppm. The percentages of survival, pupation, fecundity and egg hatch were altered at sub-lethal concentrations of Db-Precocene I (2, 4, 6 and 8 ppm, sprays on castor leaves). The observed effects were negatively correlated with concentration, with a decrease in effects as concentrations increased. Distinct changes in feeding activity and damage to gut tissues were observed upon histological examination of S. litura larvae after the ingestion of Db-Precocene I treatments. Comparative analyses of mortality on a non-target organism, the earthworm, Eisenia fetida, at equal concentrations of Precocene I and two chemical pesticides (cypermethrin and monocrotophos) produced mortality only with the chemical pesticide treatments. These results of Db-Precocene I as a highly active bioactive compound support further research to develop production from the grass D. bipinnata as an affordable resource for Precocene-I-based insecticides.     

Monitoring of the Natural Excretion of YVO4:Yb,Er Upconversion Nanoparticles from a Land Snail

Technical Physics - A method for the preparation of samples from a biological material for the detection of upconversion nanoparticles (UNPs) contained in it is proposed on the basis of confocal...     

Low-Temperature Hydrogenation of CO2 to Methanol in Water on ZnO-Supported CuAu Nanoalloys

Optimizing processes and materials for the valorization of CO₂ to hydrogen carriers or platform chemicals is a key step for mitigating global warming and for the sustainable use of renewables. We report here on the hydrogenation of CO₂ in water on ZnO-supported CuAu nanoalloys, based on ≤7 mol % Au. Cu_xAu_y/ZnO catalysts were characterized using ¹⁹⁷Au Mössbauer, in situ X-ray absorption (Au L_III- and Cu K-edges), and ambient pressure X-ray photoelectron (APXP) spectroscopic methods together with X-ray diffraction and high-resolution electron microscopy. At 200 °C, the conversion of CO₂ showed a significant increase by 34 times (from 0.1 to 3.4 %) upon increasing Cu₉₃Au₇ loading from 1 to 10 wt %, while maintaining methanol selectivity at 100 %. Limited CO selectivity (4–6 %) was observed upon increasing temperature up to 240 °C but associated with a ≈3-fold increase in CO₂ conversion. Based on APXPS during CO₂ hydrogenation in an H₂O-rich mixture, Cu segregates preferentially to the surface in a mainly metallic state, while slightly charged Au submerges deeper into the subsurface region. These results and detailed structural analyses are topics of the present contribution.     

Modeling the spread of Rubella disease using the concept of with local derivative with fractional parameter

Our aim in this work was to examine the model underpinning the spread of the Rubella virus using the novel derivative called beta‐derivative. The study of the equilibrium points together with the analysis of the disease free equilibrium points was presented. Due to the complexity of the modified equation, we introduced a new operator based on the Sumudu transform. The properties of this operator were proposed and proved in detail. We made used of this operator together with the idea of perturbation method to derive a special solution of the extended model. The stability of the method for solving this model was presented. The uniqueness of the special solution was presented, and numerical simulations were done. The graphical representations show that the model depends on both parameters and the fractional order. © 2015 Wiley Periodicals, Inc. Complexity 21: 442–451, 2016     

A Second-Order Synchrosqueezing Transform with a Simple Form of Phase Transformation

To model a non-stationary signal as a superposition of amplitude and frequency-modulated Fourier-like oscillatory modes is important to extract information, such as the underlying dynamics, hidden in the signal. Recently, the synchrosqueezed wavelet transform (SST) and its variants have been developed to estimate instantaneous frequencies and separate the components of non-stationary multicomponent signals. The short-time Fourier transform-based SST (FSST for short) reassigns the frequency variable to sharpen the time-frequency representation and to separate the components of a multicomponent non-stationary signal. However, FSST works well only with multicomponent signals having slowly changing frequencies. To deal with multicomponent signals having fast-changing frequencies, the second-order FSST (FSST2 for short) was proposed. The key point for FSST2 is to construct a phase transformation of a signal which is the instantaneous frequency when the signal is a linear chirp. In this paper we consider a phase transformation for FSST2 which has a simpler expression than that used in the literature. In the study the theoretical analysis of FSST2 with this phase transformation, we observe that the proof for the error bounds for the instantaneous frequency estimation and component recovery is simpler than that with the conventional phase transformation. We also provide some experimental results which show that this FSST2 performs well in non-stationary multicomponent signal separation.