A Selective and ''Off-On'' Fluorescent Chemosensor Based on Fluorescein for Al3+: Synthesis, Characterization, Spectroscopy Analyses, and DFT Calculation.

An efficient fluorescent cation chemosensor based on fluorescein L4 was well prepared and identified with spectroscopy analyses. UV-vis and fluorescence measurements examined the analyte complexation of the L4 with various cations, demonstrating a clear tendency to Al3+ ion. In the Job plot study, a stoichiometry ratio of a complex between L4 and Al3+ ion was determined to be 1: 2 (L4: Al3+). A stoichiometry ratio of complex between L4 and Al3+ ion was determined to be 1: 2 (L4: Al3+) using the Job plot. The association constant (Ka) of the L4-Al3+ complex was found 2.8 × 107 M-2. The obtained limit of detection (LOD) value (1.37 × 10-6 M for Al3+) exhibited the considerable sensitivity of the chemosensor L4 to Al3+ ion. DFT/TD-DFT calculations have also been employed to support the binding mode and photophysical properties of the complexation of chemosensor L4 to Al3+ ion and also to investigate the enhancement of L4 fluorescence by Al3+ ion.

Docking study, molecular dynamic, synthesis, anti-α-glucosidase assessment, and ADMET prediction of new benzimidazole-Schiff base derivatives.

The control of postprandial hyperglycemia is an important target in the treatment of type 2 diabetes mellitus (T2DM). As a result, targeting α-glucosidase as the most important enzyme in the breakdown of carbohydrates to glucose that leads to an increase in postprandial hyperglycemia is one of the treatment processes of T2DM. In the present work, a new class of benzimidazole-Schiff base hybrids 8a-p has been developed based on the potent reported α-glucosidase inhibitors. These compounds were synthesized by sample recantations, characterized by 1H-NMR, 13C-NMR, FT-IR, and CHNS elemental analysis, and evaluated against α-glucosidase. All new compounds, with the exception of inactive compound 8g, showed excellent inhibitory activities (60.1 ± 3.6-287.1 ± 7.4 µM) in comparison to acarbose as the positive control (750.0 ± 10.5). Kinetic study of the most potent compound 8p showed a competitive type of inhibition (Ki value = 60 µM). In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the title new compounds over the active site of α-glucosidase. In silico druglikeness analysis and ADMET prediction of the most potent compounds demonstrated that these compounds were druglikeness and had satisfactory ADMET profile.

Creatine@SiO2 @Fe3 O4 nanocomposite as an efficient sorbent for magnetic solid-phase extraction of escitalopram and chlordiazepoxide from urine samples through quantitation via HPLC-UV.

An efficient, cost-effective, and fast-synthesis method is presented in the current study to prepare magnetic nanoparticles covered by cheap and nitrogen-rich creatine. The hydrothermal method was used for the synthesis of the magnetic core. The prepared magnetic core was then covered by SiO2 and subsequently functionalized using creatine. The prepared creatine@SiO2 @Fe3 O4 was utilized as a sorbent in the magnetic solid-phase extraction of the selected antidepressants including escitalopram and chlordiazepoxide as the model drugs. The extracted drugs were desorbed by a suitable organic solvent and analyzed by high-performance liquid chromatography equipped with an ultraviolet detection system. The influence of different variables on the magnetic solid-phase extraction method was examined by the Plackett-Burman and Box-Behnken designs for screening and optimization, respectively. Under the obtained optimum conditions, the linear ranges of the method were found to be in the range of 1-500 µg L-1 . The limits of detection and limits of quantification were in the range of 0.27-0.63 µg L-1 and 0.89-1.93 µg L-1 for the selected analytes, respectively. Furthermore, the enrichment factors were found to be 79.8 and 92.7 for chlordiazepoxide and escitalopram, respectively. The method was successfully employed for the analysis of selected drugs in urine samples.

An experimental and mechanism study on the regioselective click reaction toward the synthesis of thiazolidinone-triazole.

An efficient procedure for the synthesis of novel thiazolidinone triazoles through 32 cycloaddition reactions in the presence of copper(I) species was described, and the molecular mechanism of this 32CA was investigated computationally. Different possible pathways for CA process have been studied to achieve this goal, including one-step pathways for both regioisomers 1,4- and 1,5-triazoles (uncatalyzed, mono-copper, di-copper) and also mono- and di-copper stepwise pathways for 1,4-disubstituted triazole. It was exhibited that the most convenient route in terms of energy barriers includes two copper ions. Based on the calculation, the reaction follows a di-copper stepwise mechanism involving the formation of a six-membered ring and then undergoes a ring contraction to a five-membered ring. The regiochemistry of the reaction was investigated based on local and global reactivity indices of reactants, the transition state stabilities calculation. The electron reorganization along the uncatalyzed one-step mechanism has been investigated by the ELF topological analysis of the bonding changes along with the CA reaction.

New Sesterterpenoids from Salvia mirzayanii Rech.f. and Esfand. Stereochemical Characterization by Computational Electronic Circular Dichroism.

Phytochemical investigation on the acetone extract of Salvia mirzayanii Rech. f. and Esfand. afforded seven new isoprenoids including six new sesterterpenoids salvimirzacolide A-F (1-6), and one new nor-diterpenoid (7). Their structures were established by comprehensive spectroscopic and spectrometric data analysis (1D and 2D NMR, HRMS) and DP4+ NMR chemical shift probability calculation technique. Moreover, the absolute configuration of compounds was determined by using electronic circular dichroism spectroscopy. Evaluation of antiproliferative properties of compounds isolated against four human melanoma cancer cells displayed no cytotoxic activity at the concentration range used.

1,2,3-Triazole-linked 5-benzylidene (thio)barbiturates as novel tyrosinase inhibitors and free-radical scavengers.

In this study, benzyl-1,2,3-triazole-linked 5-benzylidene (thio)barbiturate derivatives 7a-d and 8a-h were designed as potential tyrosinase inhibitors and free-radical scavengers. The twelve derivatives were synthesized via the [3+2] cycloaddition reaction of the corresponding benzyl azide as a dipole and the corresponding alkyne as a dipolarophile in the presence of copper(I) species, generated in situ from copper(II)/ascorbate. The thiobarbiturate derivative 8h and the barbiturate derivative 8b bearing 4-fluoro and 4-bromo groups on the benzyl-triazole moiety were found to be the most potent tyrosinase inhibitors with IC50 values of 24.6 ± 0.9 and 26.8 ± 0.8 µM, respectively. Almost all the compounds showed a good radical scavenging activity with EC50 values in the range of 29.9-324.9 µM. Derivatives 7a, 8f, and 8h were the most potent free-radical scavengers with EC50 values of 29.9 ± 0.8, 36.8 ± 0.9, and 39.2 ± 1.1 µM, respectively. The kinetic analysis revealed that compound 8h was a mixed-type tyrosinase inhibitor. The molecular docking analysis indicated that 8b and 8h were well accommodated in the active site of the tyrosinase enzyme and possessed the most negative binding energy values of -8.55 and -8.81 kcal/mol, respectively. Moreover, it was found that the two residues, Asn81 and Glu322, played a significant role in forming stable enzyme-inhibitor complexes.

Facile and efficient removal of Pb(II) from aqueous solution by chitosan-lead ion imprinted polymer network.

A new chitosan based imprinted polymer was prepared by copolymerization of 4-Vinylpyridine (VP) as a functional monomer and N,N'-Methylenebisacrylamide (MBA) as a crosslinker in the presence of Potassium peroxodisulfate (KPS) as an initiator to eliminate Pb(II) from aqueous solutions. The template ions were removed from ion imprinted polymer (IIPs) particles by leaching with 0.1 M nitric acid (HNO3) that leaves cavities in the particles with the capability of selective extraction of the Pb(II) ions. Some properties of the bioadsorbent were further identified using Field Emission Scanning Electron Microscopy (FE-SEM), Fourier Transform Infrared Spectroscopy (FT-IR) and Thermal Gravimetric Analysis (TGA). In addition, the equilibrium adsorption data were examined through Langmuir and Freundlich isotherm models and it was found that adsorption data fit well with the Freundlich isotherm. The competitive adsorption studies clearly showed that the Pb(II)-IP has a much higher adsorption capacity for Pb(II) than the non-imprinted polymer (NIP) with the same chemical composition; furthermore, it has excellent selectivity for the targeted ion. In addition, the studies regarding the regeneration and reuse studies revealed that the Pb(II)-IP beads showed no significant decrease in their adsorption capacities.

Novel N,N-dimethylbarbituric-pyridinium derivatives as potent urease inhibitors: Synthesis, in vitro, and in silico studies.

A new series of N,N-dimethylbarbituric-pyridinium derivatives 7a-n was synthesized and evaluated as Helicobacter pylori urease inhibitors. All the synthesized compounds (IC50 = 10.37 ± 1.0-77.52 ± 2.7 µM) were more potent than standard inhibitor hydroxyurea against urease (IC50 = 100.00 ± 0.2 µM). Furthermore, comparison of IC50 values of the synthesized compounds with the second standard inhibitor thiourea (IC50 = 22.0 ± 0.03 µM) revealed that compounds 7a-b and 7f-h were more potent than thiourea. Molecular modeling study of the most potent compounds 7a, 7b, 7f, and 7g was also conducted. Additionally, the drug-likeness properties of the synthesized compounds, based on Lipinski rule and other filters, were evaluated.

A new series of Schiff base derivatives bearing 1,2,3-triazole: Design, synthesis, molecular docking, and α-glucosidase inhibition.

A series of new Schiff bases bearing 1,2,3-triazole 12a-o was designed, synthesized, and evaluated as α-glucosidase inhibitors. All the synthesized compounds showed promising inhibition against α-glucosidase and were more potent than the standard drug acarbose. The kinetic study on the most potent compound 12n showed that this compound acted as a competitive α-glucosidase inhibitor. The docking study revealed that the synthesized compounds interacted with the important residues in the active site of α-glucosidase.

Preparation and application of magnetic chitosan/graphene oxide composite supported copper as a recyclable heterogeneous nanocatalyst in the synthesis of triazoles.

A magnetic chitosan-based biocomposite, MnFe2O4@GO@Chitosan/Cu, was prepared and used as an efficient heterogeneous catalyst for the synthesis of triazoles. The structure, thermal stability and magnetic properties of the composite were investigated by FT-IR, XRD, SEM, TEM, TGA, and VSM methods. The easy separation, recovery, reusability, and high yields of the products make this protocol environmentally friendly and economically attractive.

New tacrine-derived AChE/BuChE inhibitors: Synthesis and biological evaluation of 5-amino-2-phenyl-4H-pyrano[2,3-b]quinoline-3-carboxylates.

A series of poly-functionalized tacrine-derived compounds namely 5-amino-2-phenyl-4H-pyrano[2,3-b]quinoline-3-carboxylates were designed and synthesized as cholinesterases inhibitors. The in vitro inhibition assay against AChE and BuChE demonstrated that most of compounds had potent AChE inhibitory with reserving potential of BuChE inhibition. Among them, compound 6i bearing a 4-(3-bromophenyl) moiety showed the most potent activity against AChE/BuChE (IC50s values of 0.069 and 1.35 µM, respectively). The anti-AChE activity of 6i was five times more than that of tacrine. The SAR study revealed that chloro/bromo substituent at ortho or meta position of the 4-phenyl ring can improve the anticholinesterase activity.

Antioxidant and antidiabetic activities of 11 herbal plants from Hyrcania region, Iran.

In the present study, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, α-amylase and α-glucosidase inhibition activities, and total phenolic contents of n-hexane, ethyl acetate, and methanol extracts of various parts of Allium paradoxum, Buxus hyrcana, Convolvulus persicus, Eryngium caucasicum, Heracleum persicum, Pimpinella affinis, Parrotia persica, Primula heterochroma, Pyrus boissieriana, Ruscus hyrcanus, and Smilax excelsa were investigated. These plants, which mostly serve as food flavoring, were collected from Hyrcania region, Sari, Iran. Some extracts of H. persicum, S. excels, P. boissieriana, P. persica, and P. heterochroma exhibited significant antidiabetic activities in α-amylase and α-glucosidase assays, more effective than acarbose (concentrations that cause 50% inhibition = 75.7 µg/mL and 6.1 µg/mL against α-amylase and α-glucosidase, respectively). Also, C. persicus, P. boissieriana, and P. heterochroma showed strong antioxidant activities, compared with butylated hydroxytoluene (concentration that causes 50% inhibition = 16.7 µg/mL). In conclusion, this study can recommend these plants as good candidates for further investigations to find potent antidiabetic natural products or probable lead compounds. Statistical analysis showed significant correlation between the 2,2-diphenyl-1-picrylhydrazyl scavenging activity and total phenolic contents (r = 0.711, p < 0.001).

Synthesis and cytotoxic activity of novel poly-substituted imidazo[2,1-c][1,2,4]triazin-6-amines.

A novel series of 3,4-diphenyl-7-(hetero)arylimidazo[2,1-c][1,2,4]triazin-6-amine derivatives were synthesized via three-component reaction of 5,6-diphenyl-1,2,4-triazin-3-amine, various aromatic aldehydes, and cyclohexyl isocyanide. All synthesized compounds were tested against HL60 (human promyelocytic leukemia), MOLT-4 (human T lymphoblastic leukemia), and MCF-7 (human breast adenocarcinoma) cell lines, as cytotoxic agents. The structure-activity relationships study revealed that the introduction of hydroxyl and methoxy groups on the 7-phenyl ring can modulate the cytotoxic activity of these compounds. Among the 7-aryl derivatives, 3-hydroxyphenyl and 3-hydroxy-4-methoxyphenyl derivatives (6h and 6o) were the most potent compounds against HL60 and MCF-7 cells (IC(50s) = 9.8 - 20.4 µM). However, the replacement of the 7-aryl moiety with pyridyl or furan-2-yl resulted in compounds 6p or 6r with more promising cytotoxicity against MOLT-4 cell line (IC50 values 12.1 and 13.0 µM, respectively). Also, the acridine orange/ethidium bromide staining assay in MCF-7 cells suggested that the cytotoxic activity of compound 6r occurs via apoptosis.

1',5-Dinitro-2'-phenyl-2',3',5',6',7',7a'-hexa-hydro-spiro-[indoline-3,3'-1'H-pyrrolizin]-2-one.

In the title cyclo-adduct, C(20)H(18)N(4)O(5), the rings of the pyrrolizine system adopt envelope conformations. A centrosymmetric dimer is formed via inter-molecular N-H⋯O hydrogen bonds between the indolinone rings.

2'-Methyl-2'-nitro-1'-phenyl-2',3',5',6',7',7a'-hexa-hydro-spiro-[indoline-3,3'-1'H-pyrrolizin]-2-one.

The title compound, C(21)H(21)N(3)O(3), was synthesized by a multi-component 1,3-dipolar cyclo-addition of azomethine ylide, derived from isatin and proline by a deca-rboxylative route, and (E)-1-phenyl-2-nitro-propene. In the mol-ecule, the spiro junction links a planar oxindole ring and a pyrrolidine ring in an envelope conformation. The mol-ecular packing is stabilized by an inter-molecular N-H⋯N inter-action of the oxindole and pyrrolizidine rings.