Three different series of some novel N-substituted rhodanines were designed for anticancer activity and prepared from the corresponding dithiocarbamates. The synthesized compounds were analyzed by IR, NMR and MASS to confirm their structures. All the titled compounds were found to be of Z configuration based on NMR spectral analysis. All the synthesized rhodanines were screened for in vitro anticancer activity against MCF-7 breast cancer cells at the concentration of 10µg. Compounds showed moderate to significant cytotoxicity. Amongst them, interestingly, compounds 10, 22 and 33 with cinnamoyl substitution at 5 th position of thiazolidine ring system showed significant activity. Further, we subjected all these compounds for the CoMSIA study to study their 3D quantitative structure activity relationships (3D QSAR). The illustration about the design of novel rhodanines, synthesis, analysis, activity against MCF-7 cells and SAR via CoMSIA study are reported here.
A reagent-controlled chemoselective process has been
devised for
the synthesis of 4H-1,3-benzoxazines and related
biologically important heterocycles in high yields under mild conditions.
These scaffolds could be efficiently constructed using two different
chemoselective reactions that rely on the choice of reagents and reaction
conditions. The treatment of various 2-amino-arylalkyl alcohols with
isothiocyanates afforded thiourea intermediates, which were reacted in situ with molecular iodine in the presence of triethylamine
to give 2-amino-4H-1,3-benzoxazines, whereas the
corresponding 2-amino-4H-1,3-benzothiazines were
obtained by the reaction of thiourea intermediates in the presence
of T3P (a mild cyclodehydrating agent) and triethylamine as the base.
The described protocol represents the first example for the synthesis
of 4H-1,3-benzoxazines via the dehydrosulfurization
method using molecular iodine as the reagent.
BackgroundAn alarming requirement for finding newer antidiabetic glitazones as agonists to PPARγ are on its utmost need from past few years as the side effects associated with the available drug therapy is dreadful. In this context, herein, we have made an attempt to develop some novel glitazones as PPARγ agonists, by rational and computer aided drug design approach by implementing the principles of bioisosterism. The designed glitazones are scored for similarity with the developed 3D pharmacophore model and subjected for docking studies against PPARγ proteins. Synthesized by adopting appropriate synthetic methodology and evaluated for in vitro cytotoxicity and glucose uptake assay. Illustrations about the molecular design of glitazones, synthesis, analysis, glucose uptake activity and SAR via 3D QSAR studies are reported.ResultsThe computationally designed and synthesized ligands such as 2-(4-((substituted phenylimino)methyl)phenoxy)acetic acid derivatives were analysed by IR, 1H-NMR, 13C-NMR and MS-spectral techniques. The synthesized compounds were evaluated for their in vitro cytotoxicity and glucose uptake assay on 3T3-L1 and L6 cells. Further the activity data was used to develop 3D QSAR model to establish structure activity relationships for glucose uptake activity via CoMSIA studies.ConclusionThe results of pharmacophore, molecular docking study and in vitro evaluation of synthesized compounds were found to be in good correlation. Specifically, CPD03, 07, 08, 18, 19, 21 and 24 are the candidate glitazones exhibited significant glucose uptake activity. 3D-QSAR model revealed the scope for possible further modifications as part of optimisation to find potent anti-diabetic agents.
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