Therapeutic effects of soy isoflavones on α-amylase activity, insulin deficiency, liver-kidney function and metabolic disorders in diabetic rats

Natural estrogens have demonstrated a wide variety of biological activities, which makes them a good candidate for the treatment of diabetes. In vitro, this study evidenced that isoflavones enhanced insulin secretion and inhibited α-amylase activity. In vivo, the findings indicated that soy isoflavones stimulated insulin secretion, increased the hepatic glycogen content and suppressed blood glucose level. The soy isoflavones were also protected hepatic-kidney functions showed by the significant increase in superoxide dismutase, catalase and glutathione peroxidase activities and the decrease in thiobarbituric acid reactive substances, total bilirubin, creatinine and transaminases content. Moreover, soy isoflavones induced a decrease in LDL-cholesterol and triglycerides and an increase in HDL-cholesterol in plasma and liver. Overall, the findings of the current study indicate that soy isoflavones exhibit attractive properties and can, therefore, be considered a promising candidate for future application as alternative therapeutic agents, particularly in the development of anti-diabetic and hypolipidaemic drugs.     

Ln12‐Containing 60‐Tungstogermanates: Synthesis,Structure, Luminescence,and Magnetic Studies

A new class of hexameric Ln₁₂‐containing 60‐tungstogermanates, [Na(H₂O)₆?Eu₁₂(OH)₁₂(H₂O)₁₈Ge₂(GeW₁₀O₃₈)₆]^39? ( Eu₁₂ ), [Na(H₂O)₆?Gd₁₂(OH)₆(H₂O)₂₄Ge(GeW₁₀O₃₈)₆]^37? ( Gd₁₂ ), and [(H₂O)₆?Dy₁₂(H₂O)₂₄(GeW₁₀O₃₈)₆]^36? ( Dy₁₂ ), comprising six di‐Ln‐embedded {β(4,11)‐GeW₁₀} subunits was prepared by reaction of [α‐GeW₉O₃₄]^10? with Ln^III ions in weakly acidic (pH 5) aqueous medium. Depending on the size of the Ln^III ion, the assemblies feature selective capture of two (for Eu₁₂ ), one (for Gd₁₂ ), or zero (for Dy₁₂ ) extra Ge^IV ions. The selective encapsulation of a cationic sodium hexaaqua complex [Na(H₂O)₆]⁺ was observed for Eu₁₂ and Gd₁₂ , whereas Dy₁₂ incorporates a neutral, distorted‐octahedral (H₂O)₆ cluster. The three compounds were characterized by single‐crystal XRD, ESI‐MS, photoluminescence, and magnetic studies. Dy₁₂ was shown to be a single‐molecule magnet.     

Self-assembly of amphiphilic imidazolium-based hexa-peri-hexabenzocoronenes into fibreous aggregates

Imidazolium-based amphiphilic hexa-peri-hexabenzocoronenes were synthesized and shown to undergo ordered columnar self-assembly in solid-state as well as in solution to yield defined nanofibers upon solution drop casting onto solid substrate.     

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.     

Increasing the Efficacy of Seproxetine as an Antidepressant Using Charge–Transfer Complexes

The charge transfer interactions between the seproxetine (SRX) donor and π-electron acceptors [picric acid (PA), dinitrobenzene (DNB), p-nitrobenzoic acid (p-NBA), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), and 7,7′,8,8′-tetracyanoquinodi methane (TCNQ)] were studied in a liquid medium, and the solid form was isolated and characterized. The spectrophotometric analysis confirmed that the charge–transfer interactions between the electrons of the donor and acceptors were 1:1 (SRX: π-acceptor). To study the comparative interactions between SRX and the other π-electron acceptors, molecular docking calculations were performed between SRX and the charge transfer (CT) complexes against three receptors (serotonin, dopamine, and TrkB kinase receptor). According to molecular docking, the CT complex [(SRX)(TCNQ)] binds with all three receptors more efficiently than SRX alone, and [(SRX)(TCNQ)]-dopamine (CTcD) has the highest binding energy value. The results of AutoDock Vina revealed that the molecular dynamics simulation of the 100 ns run revealed that both the SRX-dopamine and CTcD complexes had a stable conformation; however, the CTcD complex was more stable. The optimized structure of the CT complexes was obtained using density functional theory (B-3LYP/6-311G++) and was compared.     

Multispectral and Molecular Docking Studies Reveal Potential Effectiveness of Antidepressant Fluoxetine by Forming π-Acceptor Complexes

Poor mood, lack of pleasure, reduced focus, remorse, unpleasant thoughts, and sleep difficulties are all symptoms of depression. The only approved treatment for children and adolescents with major depressive disorder (MDD) is fluoxetine hydrochloride (FXN), a serotonin selective reuptake inhibitor antidepressant. MDD is the most common cause of disability worldwide. In the present research, picric acid (PA); dinitrobenzene; p-nitro benzoic acid; 2,6-dichloroquinone-4-chloroimide; 2,6-dibromoquinone-4-chloroimide; and 7,7′,8,8′-tetracyanoquinodimethane were used to make 1:1 FXN charge-transfer compounds in solid and liquid forms. The isolated complexes were then characterized by elemental analysis, conductivity, infrared, Raman, and ¹H-NMR spectra, thermogravimetric analysis, scanning electron microscopy, and X-ray powder diffraction. Additionally, a molecular docking investigation was conducted on the donor moiety using FXN alone and the resulting charge transfer complex [(FXN)(PA)] as an acceptor to examine the interactions against two protein receptors (serotonin or dopamine). Interestingly, the [(FXN)(PA)] complex binds to both serotonin and dopamine more effectively than the FXN drug alone. Furthermore, [(FXN)(PA)]–serotonin had a greater binding energy than [FXN]–serotonin. Theoretical data were also generated by density functional theory simulations, which aided the molecular geometry investigation and could be beneficial to researchers in the future.     

Effect of surface conduction on the dynamics of induction charging of particles

The purpose of this paper is to investigate the dynamics of induction charging for spherical particles assuming finite volume and surface conductivities. It is assumed that the thickness of the surface layer is a small percentage of the particle radius. All results were obtained using COMSOL commercial software. The results show that the rate of charge accumulation is affected by the conductivity, permittivity and the contact area with the ground electrode. It is shown that the actual charging time constant for a material with fixed bulk properties can differ considerably from the relaxation time.