An Analytical Method for Determination of Total Iron in Pharmaceuticalgrade Intravenous Iron Colloidal Complexes by Redox-Potentiometry.

BACKGROUND: Iron carbohydrate complexes are colloidal dispersions made up of polynuclear Fe(III)-oxyhydroxide cores surrounded by a carbohydrate shell that stabilizes the complex in iron colloidal formulations. The current study provides an improved method that is precise, accurate, and linear for quantifying total iron in most Iron Carbohydrate Colloid Drug Products. METHODS: Redox iodometry with a potentiometric determination is used to evaluate total iron in intravenous formulations. The visual indicator approach is more prone to fluctuations at endpoint calculations. Hence, the voltage potential approach is widely accepted as it is more accurate and sensitive. It tracks the actual change in activity that coincides with the equivalence point that is finally considered an endpoint. The principle is based on the idea that ferric iron in formulation reduces to ferrous iron in the presence of the iodide, which oxidizes to iodine. The released iodine is titrated using sodium thiosulfate. RESULTS: The proposed method was precise, with %RSD (relative standard deviation) not more than 1. The method was linear between 80% and 120%, with a linear regression of 0.999. The percent recovery ranged from 98.20 to 99.98 for the concentration ranges of 80-120. The method's robustness was checked by various analysts using different reagent grades. CONCLUSION: The proposed potentiometric determination method was precise, accurate, linear, and sensitive. The method was successfully validated, and the total iron content determined for commercial batches agrees with the iron claim on the label. Therefore, this method can be adapted widely for total iron content determination in any Intravenous formulation currently available on the market. The proposed method is more accessible at the Quality Control facilities on an industrial scale.

Design, Synthesis and Cytotoxicity of New Coumarin-1,2,3-triazole Derivatives: Evaluation of Anticancer Activity and Molecular Docking Studies.

A library of new coumarin-1,2,3-triazole hybrids 7a-l were synthesized from 4-(diethylamino)-2-hydroxybenzaldehyde precursor through a series of reactions including Vilsmeier-Haack reaction and condensation reaction to achieve key intermediate oxime and further performed click reaction by using different aromatic azides. We screened all molecules in silico against crystal structure of Serine/threonine-protein kinase 24 (MST3), based on these results all molecules were screened for their cytotoxicity against human breast cancer MCF-7 and lung cancer A-549 cell lines. Compound 7 b (p-bromo) showed best activity against both cell lines MCF-7 and A-549 with IC50 value of 29.32 and 21.03 µM, respectively, in comparison to Doxorubicin corresponding IC50 value of 28.76 and 20.82 µM. Another compound 7 f (o-methoxy) also indicated good activity against both cell lines with IC50 value of 29.26 and 22.41 µM. The toxicity of all compounds tested against normal HEK-293 cell lines have not shown any adverse effects.

Palladium(ii)-catalyzed synthesis of indenones through the cyclization of benzenecarbaldehydes with internal alkynes.

The palladium(ii)-catalyzed carbocyclization of benzenecarbaldehydes with internal alkynes to afford 2,3-disubstituted indenones was reported. The annulation reaction proceeded through the transmetalation of Pd(ii) with an aromatic aldehyde and the insertion of internal alkynes, followed by cyclization via the intramolecular nucleophilic addition of intermediate organopalladium(ii) species to the aldehyde group. This reaction proceeded in moderate to good yields with high regioselectivity.

2,3-Dihydrofurans as Potential Cytotoxic and Antibacterial Agents: Tandem Knoevenagel-Michael Cyclization for the Synthesis of 2,3-Dihydrofurans by Using α-Tosyloxy Ketone Precursors.

Novel 2,3-dihydrofuran derivatives were synthesized through a tandem Knoevenagel-Michael cyclization in good yield by reacting α-tosyloxy ketone, 5,5-dimethyl-1,3-cyclohexanedione, and various aldehydes in the presence of phthalazine in acetonitrile. These compounds were subjected to in vitro antibacterial screening against eight micro-organisms by using diffusion method and also in vitro cytotoxicity screening against four human cancerous cell lines by applying MTT assay. Some of the compounds showed impressive activities.

An Organic Receptor Isolated in an Unusual Intermediate Conformation: Computation, Crystallography, and Hirshfeld Surface Analysis.

1,1″-1,4-Phenylene-bis(methylene)bis-4,4'-bipyridinium cation [C28H24N4]2+ (c), an organic receptor that generally crystallizes in its anti conformation, has recently been shown to be isolated in its syn conformation in an ion-paired compound [C28H24N4][Zn(dmit)2]·2DMF (dmit2- = 1,3-dithiole-2-thione-4,5-dithiolate; DMF = dimethylformamide). In this article, we demonstrated that the same receptor [C28H24N4]2+ (c) can also be stabilized in an unusual intermediate conformation (neither syn nor anti) with PF6- anion in compound [C28H24N4](PF6)2·(1,4-dioxane) (1·(1,4-dioxane)). The energetically favored anti conformation has been described in its nitrate salt [C28H24N4](NO3)2·2H2O (2·2H2O). Compounds 1·(1,4-dioxane) and 2·2H2O, crystallizing in triclinic and monoclinic systems with space groups P1̅ and P21/n, respectively, were additionally characterized by Hirshfeld surface analysis. The density functional theory calculations are performed to understand the internal mechanism of the stability of various conformers of cationic receptor c, compound 1, and compound 2. In conjunction with the electronic stability of the conformers, the natural bond orbital analysis and conformational equilibrium constants at different temperatures are also calculated to find out the sources of the different stability of the various conformers of experimentally synthesized compounds.

Construction and functionalization of pyranone ring fused with pyran moiety: design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins.

Novel pyrano[4,3-b]pyran-5(4H)-one based small molecules were designed as potential inhibitors of sirtuins (i.e., yeast sir2, a homolog of human SIRT1). Elegant synthesis of these compounds was performed via a multi-step sequence consisting of MCR, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C-C bond forming reactions. The overall strategy involved the construction of a pyran ring followed by the fused pyranone moiety and subsequent functionalization at C-8 position of the resultant core pyrano[4,3-b]pyran-5(4H)-one framework. The crystal structure analysis of a representative iodolactonized product (6d) is presented. Some of the synthesized compounds showed promising inhibitory activities when tested against yeast sir2 in vitro. The compound 6g showed dose dependent inhibition (IC50=78.05µM) of yeast sir2 and good interactions with this protein in silico.

Amberlite IR-120H catalyzed MCR: design, synthesis and crystal structure analysis of 1,8-dioxodecahydroacridines as potential inhibitors of sirtuins.

A rapid, inexpensive and high yielding method has been developed for the synthesis of 1,8-dioxodecahydroacridines using Amberlite IR-120H as a reusable catalyst under open air. These compounds were designed as potential inhibitors of sirtuins and prepared via the MCR of 5,5-dimethyl-1,3-cyclohexanedione, (hetero)aryl aldehydes and (hetero)aromatic amines under mild conditions. Further structure elaboration of a representative compound was performed via Pd catalyzed C-C bond forming reactions. The crystal structure analysis and H-bonding patterns along with in vitro inhibitory activity against yeast Sir2 of the same compound is presented. Docking studies indicated that the compound interacts well with the yeast Sir2.

Pyrrolo[2,3-b]quinoxalines as inhibitors of firefly luciferase: their Cu-mediated synthesis and evaluation as false positives in a reporter gene assay.

2-Substituted pyrrolo[2,3-b]quinoxalines having free NH were prepared directly from 3-alkynyl-2-chloroquinoxalines in a single pot by using readily available and inexpensive methane sulfonamide (or p-toluene sulfonamide) as an ammonia surrogate. The reaction proceeded in the presence of Cu(OAc)(2) affording the desired product in moderate yield. The crystal structure analysis of a representative compound and its supramolecular interactions are presented. Some of the compounds synthesized exhibited inhibitory activities against luciferase that was supported by the predictive binding mode of these compounds with luciferase enzyme through molecular docking studies. The key observations disclosed here can alert users of luciferase reporter gene assays for possible false positive results due to the direct inhibition of luciferase.

Thieno[3,2-c]pyran-4-one based novel small molecules: their synthesis, crystal structure analysis and in vitro evaluation as potential anticancer agents.

Novel thieno[3,2-c]pyran-4-one based small molecules were designed as potential anticancer agents. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of few steps such as Gewald reaction, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C-C bond forming reactions. The overall strategy involved the construction of thiophene ring followed by the fused pyranone moiety and then functionalization at C-7 position of the resultant thieno[3,2-c]pyran-4-one framework. Some of the compounds synthesized showed selective growth inhibition of cancer cells in vitro among which two compounds for example, 5d and 6c showed IC(50) values in the range of 2.0-2.5 µM. The crystal structure analysis of an active compound along with hydrogen bonding patterns and molecular arrangement present within the molecule is described.