A review: Biologically active 3,4-heterocycle-fused coumarins.

The combination of heterocycles offers a new opportunity to create novel multicyclic compounds having improved biological activity. Coumarins are ubiquitous natural heterocycle widely adopted in the design of various biologically active compounds. Fusing different heterocycles with coumarin ring is one of the interesting approaches to generating novel hybrid molecules having highlighted biological activities. In the efforts to develop heterocyclic-fused coumarins, a wide range of 3,4-heterocycle-fused coumarins have been introduced bearing outstanding biological activity. The effect of heterocycles annulation at 3,4-positions of coumarin ring on the biological activity of the target structures were discussed. This review focuses on the important progress of 3,4-heterocycle-fused coumarins providing better insight for medicinal chemists on the design and preparation of biologically active heterocycle-fused coumarins with a significant therapeutic effect in the future.

Magnetic carnosine-based metal-organic framework nanoparticles: fabrication, characterization and application as arsenic adsorbent.

This study centers on the controllable synthesis, characterization, and application of a novel magnetic bio-metal-organic framework (Bio-MOF) for the adsorption and subsequent removal of arsenic from aqueous solutions. Zinc ions and carnosine (Car) were exploited to construct the Car-based MOF on the surface of magnetite (Fe3O4 NPs). The Magnetite precoating with Car led to an increase in the yield and the uniform formation of the magnetic MOF. The prepared magnetic Bio-MOF nanoparticles (Fe3O4-Car-MOF NPs) had semi-spherical shape with the size in the range of 35-77 nm, and the crystalline pattern of both magnetite and Car-based MOF. The NPs were employed as an adsorbent for arsenic (As) removal. The adsorption analyses revealed that all studied independent variables including pH, adsorbent dose, and initial arsenic concentration had a significant effect on the arsenic adsorption, and the adsorption data were well matched to the quadratic model. The predicted adsorption values were close to the experimental values confirming the validity of the suggested model. Furthermore, adsorbent dose and pH had a positive effect on arsenic removal, whereas arsenic concentration had a negative effect. The adsorption isotherm and kinetic studies both revealed that As adsorption fitted best to the Freundlich isotherm model. The maximum monolayer adsorption capacity (94.33 mg/g) was achieved at room temperature, pH of 8.5 and adsorbent dose of 0.4 g/L. Finally, the results demonstrated that the adsorbent could be efficiently applied for arsenic removal from aqueous environment.

Folic acid decorated magnetic nanosponge: An efficient nanosystem for targeted curcumin delivery and magnetic resonance imaging.

Magnetic drug delivery system is one of the most important strategies for cancer diagnosis and treatment. In this study, a novel theranostic system was fabricated based on cyclodextrin nanosponge (CDNS) polymer anchored on the surface of Magnetite nanoparticles (Fe3O4/CDNS NPs) which was then decorated with folic acid (FA) as a targeting agent (Fe3O4/CDNS-FA). Curcumin (CUR), a hydrophobic model drug, was next loaded into the cyclodextrin cavity and polymeric matrix of CDNS (Fe3O4/CDNS-FA@CUR). The system was fully characterized. The in vitro release study revealed pH-sensitive behavior. Cytotoxicity assays indicated a negligible toxicity for CUR free Fe3O4/CDNS-FA NPs against both of M109 cancerous cells and MCF 10A normal cells. CUR-loaded Fe3O4/CDNS-FA NPs exhibited higher toxicity against M109 cancerous cells than MCF 10A normal cells (p < 0.05). Fe3O4/CDNS-FA@CUR NPs resulted in much more cell viability on normal cells than pure CUR (p < 0.05). Moreover, blood compatibility study showed minor hemolytic activity. In vitro MRI studies illustrated negative signal increase in cells affirming acceptable diagnostic ability of the nanocarrier. The T2 MR signal intensity for Fe3O4/CDNS-FA@CUR NPs in M109 cells was around 2-fold higher than that of MCF 10A cells. This implies two times higher selective cellular uptake of the Fe3O4/CDNS-FA@CUR NPs into M109 cell compared to MCF 10A. The multifunctional nanocarrier could be considered as promising candidate for cancer theranostics because of the smart drug release, selective cytotoxicity, suitable hemocompatibility, and proper T2 MRI contrast efficiency.

New classes of carbazoles as potential multi-functional anti-Alzheimer's agents.

Multi-Target approach is particularly promising way to drug discovery against Alzheimer's disease. In the present study, we synthesized a series of compounds comprising the carbazole backbone linked to the benzyl piperazine, benzyl piperidine, pyridine, quinoline, or isoquinoline moiety through an aliphatic linker and evaluated as cholinesterase inhibitors. The synthesized compounds showed IC50 values of 0.11-36.5 µM and 0.02-98.6 µM against acetyl- and butyrylcholinesterase (AChE and BuChE), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 3s could bind effectively to the peripheral anionic binding site (PAS) and anionic site of the enzyme with mixed-type inhibition. Compound 3s was the most potent compound against AChE and BuChE and showed acceptable inhibition potency for self- and AChE-induced Aß1-42 aggregation. Moreover, compound 3s could significantly protect PC12 cells against H2O2-induced toxicity. The results suggested that the compounds 3s could be considered as a promising multi-functional agent for further drug discovery development against Alzheimer's disease.

Improved curcumin loading, release, solubility and toxicity by tuning the molar ratio of cross-linker to ß-cyclodextrin.

A novel ß-cyclodextrin-based nanosponge (CDNS) was proposed as curcumin (CUR) delivery system improving pharmacokinetics and anticancer activity of CUR. The effect of molar ratio of Epiclon (EPI) as cross-linker and ß-cyclodextrin (ßCD) on the porosity, surface area, swelling ratio, CUR solubility and loading capacity, rate of drug release and selective toxicity of the CDNSs was fully investigated. The high degree of cross-linking led to the formation of mesoporous CDNS having high specific surface area and high loading capacity. All CUR-free CDNSs showed no toxicity against MCF 10A and 4T1 cells as normal and cancerous cells, respectively. While CDNSs-CUR exhibited selective toxicity against cancerous cells. In sum, high CUR aqueous solubility, significant loading and controllable release of the CUR, outstanding and selective toxicity against cancerous cells make CDNS8-CUR (EPI/ßCD = 8) as promising candidate for further study in the cancer therapy.

Glutathione conjugated polyethylenimine on the surface of Fe3O4 magnetic nanoparticles as a theranostic agent for targeted and controlled curcumin delivery.

Theranostics with the ability to simultaneous monitoring of treatment progress and controlled delivery of therapeutic agents has become as an emerging therapeutic paradigm in cancer therapy. In this study, we have developed a novel surface functionalized iron oxide nanoparticle using polyethyleneimine and glutathione for targeted curcumin (CUR) delivery and acceptable pH sensitive character. The developed magnetic nanoparticles (MNPs) were physicochemically characterized by FT-IR, XRD, FE-SEM and TEM. The MNPs was obtained in spherical shape with diameter of 50 nm. CUR was efficiently loaded into the MNPs and then in vitro release analyses were evaluated and showed that the prepared MNPs could release higher amount of CUR in acidic medium compared to neutral medium due to the pH sensitive property of the coated polymer. MTT assay confirmed the superior toxicity of CUR loaded MNPs compared to the control nanoparticles. Higher cellular uptake of the MNPs than negative control cells was demonstrated in SK-N-MC cell line. In vitro assessment of MRI properties showed that synthesized MNPs could be used as MRI imaging agent. Furthermore, according to hemolysis assay, the developed formulation exhibited suitable hemocompatibility. In vivo blood circulation analysis of the MNPs also exhibited enhanced serum bioavailability up to 2.5 fold for CUR loaded MNPs compared with free CUR.

Localized template-driven functionalization of nanoparticles by dynamic combinatorial chemistry.

We have developed a method for the localized functionalization of gold nanoparticles using imine-based dynamic combinatorial chemistry. By using DNA templates, amines were grafted on the aldehyde-functionalized nanoparticles only if and where the nanoparticles interacted with the template molecules. Functionalization of the nanoparticles was controlled solely by the DNA template; only amines capable of interacting with DNA were bound to the surface. Interestingly, even though our libraries contained only a handful of simple amines, the DNA sequence influenced their attachment to the surface. Our method opens up new opportunities for the synthesis of multivalent, nanoparticle-based receptors for biomacromolecules.

The use of antibacterial activity of ZnO nanoparticles in the treatment of municipal wastewater.

Nanotechnology holds great potential in advanced water and wastewater treatment to improve treatment efficiency. Zinc oxide nanoparticles (ZnO NPs) have received considerable attention due to their unique antibacterial activities toward various microorganisms that are commonly found in the environment. In the present study, ZnO NPs were synthesized through both mechano-chemical and sol-gel methods. The synthesized ZnO NPs were characterized through X-ray diffraction and transmission electron microscopy techniques. Then, their antibacterial activities against separated wastewater bacteria were evaluated by determining the zone inhibitor, the minimum inhibitory concentration, and the minimum bactericidal concentration. The results were compared with those obtained from wastewater after chlorine disinfection and ultraviolet (UV) disinfection. These studies demonstrated that the antibacterial activity of ZnO NPs depends on the type and the strain of bacteria. They have also demonstrated that the activity increases as the concentration of ZnO NPs increases. Overall, the experimental results suggest that ZnO NPs can potentially be an antibacterial reagent to treat wastewater. They can particularly be applied as a complementary method with UV disinfection. Thus, they can be developed as antibacterial agents to improve wastewater quality.