Resveratrol-Laden Nano-Systems in the Cancer Environment: Views and Reviews.

The genesis of cancer is a precisely organized process in which normal cells undergo genetic alterations that cause the cells to multiply abnormally, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Potential drugs that could modify these carcinogenic pathways are the ones that will be used in clinical trials as anti-cancer drugs. Resveratrol (RES) is a polyphenolic natural antitoxin that has been utilized for the treatment of several diseases, owing to its ability to scavenge free radicals, control the expression and activity of antioxidant enzymes, and have effects on inflammation, cancer, aging, diabetes, and cardioprotection. Although RES has a variety of pharmacological uses and shows promising applications in natural medicine, its unpredictable pharmacokinetics compromise its therapeutic efficacy and prevent its use in clinical settings. RES has been encapsulated into various nanocarriers, such as liposomes, polymeric nanoparticles, lipidic nanocarriers, and inorganic nanoparticles, to address these issues. These nanocarriers can modulate drug release, increase bioavailability, and reach therapeutically relevant plasma concentrations. Studies on resveratrol-rich nano-formulations in various cancer types are compiled in the current article. Studies relating to enhanced drug stability, increased therapeutic potential in terms of pharmacokinetics and pharmacodynamics, and reduced toxicity to cells and tissues are the main topics of this research. To keep the readers informed about the current state of resveratrol nano-formulations from an industrial perspective, some recent and significant patent literature has also been provided. Here, the prospects for nano-formulations are briefly discussed, along with machine learning and pharmacometrics methods for resolving resveratrol's pharmacokinetic concerns.

Reduced Graphene Oxide-Zinc Sulfide Nanocomposite Decorated with Silver Nanoparticles for Wastewater Treatment by Adsorption, Photocatalysis and Antimicrobial Action.

Reduced graphene oxide nanosheets decorated with ZnS and ZnS-Ag nanoparticles are successfully prepared via a facile one-step chemical approach consisting of reducing the metal precursors on a rGO surface. Prepared rGO-ZnS nanocomposite is employed as an adsorbent material against two model dyes: malachite green (MG) and ethyl violet (EV). The adsorptive behavior of the nanocomposite was tuned by monitoring some parameters, such as the time of contact between the dye and the adsorbent, and the adsorbent dose. Experimental data were also simulated with kinetic models to evaluate the adsorption behavior, and the results confirmed that the adsorption of both dyes followed a pseudo 2nd order kinetic mode. Moreover, the adsorbent was also regenerated in a suitable media for both dyes (HCl for MG and ethanol for EV), without any significant loss in removal efficiency. Ag doped rGO-ZnS nanocomposite was also utilized as a photocatalyst for the degradation of the selected organic contaminant, resorcinol. The complete degradation of the phenolic compound was achieved after 60 min with 200 mg of rGO-ZnS-Ag nanocomposite under natural sunlight irradiation. The photocatalytic activity was studied considering some parameters, such as the initial phenol concentration, the photocatalyst loading, and the pH of the solution. The degradation kinetics of resorcinol was carefully studied and found to follow a linear Langmuir-Hinshelwood model. An additional advantage of rGO-ZnS and rGO-ZnS-Ag nanocomposites was antibacterial activity against Gram-negative bacterium, E. coli, and the results confirmed the significant performance of the nanocomposites in destroying harmful pathogens.

Differences in structural elements of Bcr-Abl oncoprotein isoforms in Chronic Myelogenous Leukemia.

in silico modeling, using Psipred and ExPASy servers was employed to determine the structural elements of Bcr-Abl oncoprotein (p210(BCR-ABL)) isoforms, b2a2 and b3a2, expressed in Chronic Myelogenous Leukemia (CML). Both these proteins are tyrosine kinases having masses of 210-kDa and differing only by 25 amino acids coded by the b3 exonand an amino acidsubstitution (Glu903Asp). The secondary structure elements of the two proteins show differences in five α-helices and nine ß-strands which relates to differences in the SH3, SH2, SH1 and DNA-binding domains. These differences can result in different roles played by the two isoforms in mediating signal transduction during the course of CML.

Binding interactions of porphyrin derivatives with Ca(2+) ATPase of sarcoplasmic reticulum (SERCA1a).

The use of Porphyrin derivatives as photosensitizers in Photodynamic Therapy (PDT) was investigated by means of a molecular docking study. These molecules can bind to intracellular targets such as P-type CaCa(2+) ATPase of sarcoplasmic reticulum (SERCA1a). CAChe software was successfully employed for conducting the docking of Tetraphenylporphinesulfonate(TPPS), 5,10,15,20- Tetrakis (4-sulfonatophenyl) porphyrinato Iron(III) Chloride (FeTPPS) and 5,10,15,20-Tetrakis (4-sulfonatophenyl) porphyrinato Iron(III) nitrosyl Chloride (FeNOTPPS) with CaCa(2+) ATPase from sarcoplasmic reticulum of rabbit. The results show that FeNOTPPS forms the most stable complex with CaCa(2+) ATPase.

New route to ABCD-porphyrins via bilanes.

A new strategy for preparing porphyrins that bear up to four different meso-substituents (ABCD-porphyrins) relies on two key reactions. One key reaction entails a directed synthesis of a 1-protected 19-acylbilane by acid-catalyzed condensation at high concentration (0.5 M) of a 1-acyldipyrromethane and a 9-protected dipyrromethane-1-carbinol (derived from a 9-protected 1-acyldipyrromethane). Three protecting groups (X) were examined, including thiocyanato, ethylthio, and bromo, of which bromo proved most effective. The bilanes were obtained in 72-80% yield, fully characterized, and examined by 15N NMR spectroscopy. The second key reaction entails a one-flask transformation of the 1-protected 19-acylbilane under basic, metal-templating conditions to give the corresponding metalloporphyrin. The reaction parameters investigated for cyclization of the bilane include solvent, metal salt, base, concentration, temperature, atmosphere, and time. The best conditions entailed the 1-bromo-19-acylbilane at 100 mM in toluene containing DBU (10 mol equiv) and MgBr2 (3 mol equiv) at 115 degrees C exposed to air for 2 h, which afforded the magnesium porphyrin in 65% yield. The magnesium porphyrin is readily demetalated to give the free base porphyrin. A stepwise procedure (which entailed treatment of the 1-(ethylthio)-19-acylbilane to oxidation, metal complexation, desulfurization, carbonyl reduction, and acid-catalyzed condensation) was developed but was much less efficient than the one-flask process. The new route to ABCD-porphyrins retains the desirable features of the existing "2 + 2" (dipyrromethane + dipyrromethane-1,9-dicarbinol) method, such as absence of scrambling, yet has significant advantages. The advantages include the absence of acid in the porphyrin-forming step, the use of a metal template for cyclization, the ability to carry out the reaction at high concentration, the lack of a quinone oxidant, avoidance of use of dichloromethane, and the increased yield of macrocycle formation to give the target ABCD-metalloporphyrin.

9-Acylation of 1-acyldipyrromethanes containing a dialkylboron mask for the alpha-acylpyrrole motif.

1,9-Diacyldipyrromethanes are important precursors to porphyrins, yet synthetic access remains limited owing to (1) poor conversion in the 9-acylation of 1-acyldipyrromethanes and (2) handling difficulties because acyldipyrromethanes typically streak upon chromatography and give amorphous powders upon attempted crystallization. A reliable means for converting a dipyrromethane to a 1-acyldipyrromethane-dialkylboron complex was recently developed, where the dialkylboron (BR(2)) unit renders the complex hydrophobic and thereby facilitates isolation. Herein a refined preparation of 1,9-diacyldipyrromethanes is presented that employs the 1-acyldipyrromethane-BR(2) complex as a substrate for 9-acylation. The dialkylboron unit provides protection for the alpha-acylpyrrole unit. 9-Acylation requires formation of the pyrrolyl-MgBr reagent and the presence of 1 equiv of a nonnucleophilic base to quench the proton liberated upon alpha-acylation. Reaction of the 1-acyldipyrromethane-BR(2) complex (1 equiv) with mesitylmagnesium bromide (2 equiv) followed by the addition of an acylating agent (S-2-pyridyl thioate or acid chloride, 1.1 equiv) gives the corresponding 1,9-diacyldipyrromethane-BR(2) complex. The acylation method afforded 1,9-diacyldipyrromethane-BR(2) complexes with limited or no chromatography in yields of 64-92%. The 1,9-diacyldipyrromethane-BR(2) complexes are stable to routine handling, are readily soluble in common organic solvents, crystallize readily, and can now be prepared in multigram quantities through use of stoichiometric quantities of reagents.