No abstract

Organosulfates and sulfamates are important classes of bioactive molecules but due to their polar nature, they are both difficult to prepare and purify. We report an operationally simple, double ion-exchange method to access organosulfates and sulfamates. Inspired by the novel sulfating reagent, TriButylSulfoAmmonium Betaine (TBSAB), we developed a 3-step procedure using tributylamine as the novel solubilising partner coupled to commercially available sulfating agents. Hence, in response to an increasing demand for complementary methods to synthesise organosulfates, we developed an alternative sulfation route based on an inexpensive, molecularly efficient and solubilising cation exchanging method using off-the-shelf reagents. The disclosed method is amenable to a range of differentially substituted benzyl alcohols, benzylamines and aniline and can also be performed at low temperature for sensitive substrates in good to excellent isolated yield.

Aims: The aim of this study was to synthesize and evaluate the biological activity of newer pyrazole derivatives. Background: Cancer is one of the world's top noncommunicable disease growing rapidly with an approximately 18.1 million new cases and 10 million deaths in the last year. Despite the availability of numerous classes of anticancer agents, treatment for all types of cancers is still a long way due to severe adverse drug reactions and drug resistance. Therefore, there is a pressing need to develop newer safer and effective anticancer agents. Objective: Our objective in this study was the greener one-pot synthesis of newer pyrazole derivatives with solvent-free method as an alternative strategy for synthesizing new agents with potential anticancer activity. Method: Herein, we describe the expedient synthesis of pyrazoles by one-pot three-component condensation of ethyl acetoacetate/acetyl acetone, isoniazide and aryldiazonium salts under solvent free conditions and evaluation of cytotoxicity by Sulforhodamine B assay on three cancer cell lines. The molecular docking studies employing tyrosine kinase were also carried out to evalutae the binding mode of newer pyrazole derivatives. Result: Among ten newly synthesised pyrazolyl analogues, 2-isonicotinoyl-5-methyl-4-(2-(4-nitrophenyl)hydrazono)-2,4-dihydro-3H-pyrazol-3-one (1f) displayed promising anticancer activity against the MCF-7, HepG2 and HCT-116 cell lines with IC50 value of 0.2-3.4 μM. Conclusion: In summary, our findings suggested that pyrazolyl analogues containing hydrozono/diazenyl pharmacophore are promising scaffold for the development of newer anticancer agents.

SIGNIFICANCEThe current study is the first report to describe the improvement of ferning patterns of human tears using electrolyte solutions. The results can help in the production of new artificial tears to improve the quality of tears.PURPOSEThis study aimed to investigate the effect of the addition of different volumes of various electrolyte solutions on ferning patterns of human tears.METHODSTear samples (20 μL) were collected from the right eye of 13 subjects (5 men and 5 women) aged 19 to 36 years (27.1 ± 5.1 years) with normal eyes. Then, 1 μL of each tear sample was dried on a microscopic glass slide, and obtained ferns were observed using light microscopy and graded using the 5-point tear ferning (TF) grading scale. Homogenous mixtures of each tear sample (0.5 μL) and different volumes (0.5 to 5 μL) of each electrolyte were prepared. A sample (1 μL) of each mixture was dried, and the ferns obtained were graded and compared with those of the corresponding tears collected from subjects before the addition of electrolyte solutions.RESULTSAfter the addition of electrolyte solutions, the TF grades of tears collected from healthy humans were generally improved. Significant (Wilcoxon test) improvements have been seen in the TF grades of the tear samples after the addition of a solution of potassium chloride (P = .03), calcium chloride (P = .01), magnesium chloride hexahydrate (P = .002), and sodium dihydrogen phosphate (P = .002). No significant improvements in the TF grades were seen after the addition of sodium chloride solution (P = .33).CONCLUSIONSFerning grades of human tears improved with most of the electrolytes used.

The treatment of common steroids: estrone, estradiol, cortisol, and pregnenolone with tributylsulfoammonium betaine (TBSAB) provides a convenient chemoselective conversion of the steroids alcohol/phenol moiety to the corresponding steroidal organosulfate. An important feature of the disclosed methodology is the millimolar scale of the reaction, and the isolation of the corresponding steroid sulfates as their biologically relevant sodium salts without the need for ion-exchange chromatography. The scope of the method was further explored in the estradiol and pregnanediol steroid systems with the bis-sulfated derivatives. Ultimately, a method to install an isotopic label, deuterium (2H) combined with estrone sulfation is a valuable tool for its mass-spectrometric quantification in biological studies.