کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5512549 1540225 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Quinazoline derivatives as cathepsins B, H and L inhibitors and cell proliferating agents
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Quinazoline derivatives as cathepsins B, H and L inhibitors and cell proliferating agents
چکیده انگلیسی
Cysteine Cathepsins well known to be involved in cancer, inflammation and regulation of degenerative processes like apoptosis have become specific targets in drug designing. The potential of quinazolines and their derivatives in medicinal chemistry led us to synthesise a novel series of seven compounds of quinazolines to evaluate their effect on cathepsins and cellular aspects of HepG2 cells. In the present work we report the solvent free microwave assisted synthesis of (E)-8-benzylidene-5,6,7,8-tetrahydro-2,4-diarylquinazolines as inhibitors of mammalian hepatic cysteine proteases viz. Cathepsins B, H and L. In vitro inhibition of Cathepsins B, H and L is correlated well with in vitro studies when tested using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay on HepG2 cells, hepatocellular carcinoma cell line. The studies have been extended to evaluate the type of inhibition exhibited by the individual enzyme. Out of the seven compounds 1g i.e. (E)-8-(4-fluorobenzylidene)-4-(4-fluorophenyl)-2-phenyl-5, 6, 7, 8-tetrahydroquinazoline has been found to be most inhibitory for Cathepsins B, H and L to a maximum extent with the Ki values of 10−10 M, 10−10 M and 10−9 M order respectively. In silico studies of all compounds have also been done at the active sites of Cathepsin B, H and L.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 94, Part A, January 2017, Pages 719-727
نویسندگان
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