A rapid, transition metal-free, high-yielding,
tetrabutylammonium
bromide-promoted method of N-arylation is reported within. The optimized
conditions tolerated a wide range of secondary amines and was equally
effective with bromo- and chlorobenzene-including substituted aryl
halides. The developed method is found to be effective for N-arylation
when compared to earlier methods which involve harsh conditions, transition
metals, lack of scalability, and long reaction times. Our method utilizes
conventional heating only; it is readily scalable; and the products
are facile to purify.
Dithiolethiones are five-membered sulfur-containing cyclic scaffolds that exhibit antioxidative, anti-inflammatory, antithrombic and chemotherapeutic activities. Dithiolethiones display the chemopreventive and cytoprotective effects by activating the antioxidant response element and mounting the transcription of cytoprotective phase II enzymatic machinery. In addition, several classes of dithiolethiones efficiently modulate the activities of proteins that play crucial roles in normal and cancer cells, including glutathione S-transferase, cyclooxygenases and master regulator NF-κB. The present paper summarizes synthetic aspects, pharmacological potentials and biological attributes of dithiolethiones and its derivatives. Additionally, this review concludes with a discussion on how the current state-of-the-art technologies may help in defining a structure-activity relationship of dithiolethiones, thereby facilitating the design and synthesis of potent drug candidates.
We identified a new dual-acting anti-breast cancer molecules as a proof of concept which is capable of targeting both ER-positive and ER-negative breast cancer.
Several new coumarin and chromene prototype derivatives have been synthesised and evaluated for their ERa and ERb selective activity. Coumarin prototype compounds 18 & 19 were found to be ERa selective and the most active, exhibiting potential antiproliferative activity against both ER +ve & ER Àve breast cancer cell lines. The surprise finding of the series, however, are the novel prototype III chromenes 45 & 46, with aroyl substitution at the 6 th position. Both the compounds have shown potent antiproliferative activity against both the breast cancer cell lines, promote alkaline phosphatase activity, enhance osteoblast mineralization in vitro, significantly decrease ERE-ERa dependent transactivation and induce ERb activity. This specific upregulation of ERb isoform activity of compound 45 may be responsible for the antiosteoporotic activity at picomolar concentration. In addition, both the compounds were also devoid of any estrogenic activity, which correlates to their antiestrogenic behaviour in the two breast cancer cell lines. Assessment of selectivity using specific SiRNAs for ERa and ERb revealed that most of the compounds showed ERa and ERb-mediated action, except compound 28, which showed selectivity to ERa only. Computational docking analysis of active compounds 18 and 45 was conducted to correlate the interaction with the two receptors and it was found that the docked conformations of the coumarin prototype, compound 18 at ERa and ERb active sites were more or less superimposable on each other. However, the unique orientation of the aminoalkoxy side chain of novel chromene (prototype III) compound 45 in the ERb binding cavity may be responsible for its potential biological response.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.