An improved synthesis of isonitrosoacetanilides

A novel two-step synthesis of isonitrosoacetanilides [2-(hydroxyimino)-N-phenylacetamides] has been developed, involving the initial acylation of aniline derivatives with 2,2-diacetoxyacetyl chloride, followed by reaction with hydroxylamine hydrochloride. The method works equally well with a variety of different aniline derivatives, including those with poor aqueous solubility and those containing electron rich ortho-substituents, neither of which react well under traditional conditions.     

Benzothiazolium derivatives. III. Nucleophilic substitution reactions of benzothiazolium salts

The reactions of 2,3-dihydrothiazolo[2,3-b]benzothiazolium bromide 1 (A^? ?Br^?) with certain nucleophilic reagents have been performed for the purpose of ascertaining the reaction pathways and identifying the group that is displaced from the central carbon atom of the dithiocarbamate system. The nature of complex salt-like intermediates formed initially from 1 (A^? ?Br^?) has been studied and confirmed. For comparison, a number of nucleophilic substitution reactions of 2-methylthio-3-methylbenzothiazolium iodide 17 and 2-dimethylamino-3-methylbenzothiazolium perchlorate 18 have been examined.     

A new short synthesis of 3-substituted 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indoles (amino-CBIs)

A new short synthesis of 3-substituted 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indoles from Martius Yellow is disclosed. The key steps of the synthesis were three efficient regioselective reactions (iodination, 5-exo-trig aryl radical-alkene cyclization and carboxylation).     

An Efficient Large Scale Synthesis of 2-Methoxytetrahydrophenanthridine.

A practical and high yielding synthesis of 2-methoxy-7,8,9,10-tetrahydrophenanthridine suitable for large-scale preparation is described.     

Conjugation of Palbociclib with MHI-148 Has an Increased Cytotoxic Effect for Breast Cancer Cells and an Altered Mechanism of Action

The CDK4/6 inhibitor palbociclib, combined with endocrine therapy, has been shown to be effective in postmenopausal women with estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer. However, palbociclib is not as effective in the highly aggressive, triple-negative breast cancer that lacks sensitivity to chemotherapy or endocrine therapy. We hypothesized that conjugation of the near-infrared dye MHI-148 with palbociclib can produce a potential theranostic in triple-negative, as well as estrogen receptor-positive, breast cancer cells. In our study, the conjugate was found to have enhanced activity in all mammalian cell lines tested in vitro. However, the conjugate was cytotoxic and did not induce G1 cell cycle arrest in breast cancer cells, suggesting its mechanism of action differs from the parent compound palbociclib. The study highlights the importance of investigating the mechanism of conjugates of near-infrared dyes to therapeutic compounds, as conjugation can potentially result in a change of mechanism or target, with an enhanced cytotoxic effect in this case.     

Synergistic effect of dealumination and ceria impregnation to the catalytic properties of MOR zeolite

MOR zeolite has been extensively employed as a catalyst in industries. However, high Brønsted acidity in MOR leads to rapid deactivation due to coke deposition on the pore mouths; thus, the surface acidity of MOR needs to be moderated. Herein, we report a modification of MOR chemical composition via acid treatment and deposition of ceria nanoparticles using a wet impregnation method. The acid treatment successfully increases the Si/Al ratio of MOR from 8.39 to 11.58 and reduces the total acid site concentration of MOR from 990 μmol/g to 752 μmol/g. The acidity of MOR is decreased when the Si/Al ratio is increased since the quantity of Brønsted acid sites is proportional to the number of Al framework. In addition, the acid treatment also improves the external surface area of MOR. Furthermore, ceria particles were successfully deposited on the MOR surface using wet impregnation method. The ceria content of parent MOR sample is lower compared to that of preceded by the acid treatment, which may be attributed to the formation of more terminal silanol groups. Finally, catalytic test on Friedel–Crafts alkylation of toluene with benzyl alcohol shows that the synergy between dealumination and the impregnation of ceria significantly improves the activity of MOR zeolite.     

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

Doxorubicin is a widely used and promising anticancer drug; however, a severe dose-dependent cardiotoxicity hampers its therapeutic value. Doxorubicin may cause acute and chronic issues, depending on the duration of toxicity. In clinical practice, the accumulative toxic dose is up to 400 mg/m² and increasing the dose will increase the probability of cardiac toxicity. Several molecular mechanisms underlying the pathogenesis of doxorubicin cardiotoxicity have been proposed, including oxidative stress, topoisomerase beta II inhibition, mitochondrial dysfunction, Ca²⁺ homeostasis dysregulation, intracellular iron accumulation, ensuing cell death (apoptosis and necrosis), autophagy, and myofibrillar disarray and loss. Natural products including flavonoids have been widely studied both in cell, animal, and human models which proves that flavonoids alleviate cardiac toxicity caused by doxorubicin. This review comprehensively summarizes cardioprotective activity flavonoids including quercetin, luteolin, rutin, apigenin, naringenin, and hesperidin against doxorubicin, both in in vitro and in vivo models.     

Cyclosporin Measurement – who cares about inaccuracy?

Most medical laboratories measure the immunosuppressive drug cyclosporin using one of a number of commercial immunoassays, or high-performance liquid chromatography (HPLC). The calibration of these assays is based on material supplied by the kit manufacturers or prepared in-house. We have examined inaccuracy for the measurement of cyclosporin in samples spiked to known concentrations and the impact of any inaccuracy on the results for cyclosporin measurement in pooled samples from patients prescribed the drug. The data were from the International Cyclosporin Proficiency Testing Scheme, based on aliquots of cyclosporin-free blood to which known amounts of the drug had been added or aliquots of pooled samples collected from patients receiving cyclosporin. Compared with the results using HPLC, the immunoassays had a median bias which ranged from –4.5% to 8.2% for the spiked samples. When pooled samples from patients were analysed the percentage difference from the measured HPLC value, allowing for assay inaccuracy, was as high as 29.9%. It is concluded that inaccuracy is a factor in between-assay performance for this measurement and that proficiency testing schemes should attempt to put more emphasis on this aspect of assay performance.