کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1363164 981504 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis, DNA intercalation and 3D QSAR analysis of cis-2,4,5-trisubstituted-1,3-dithiolanes as a novel class of antitumor agents
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis, DNA intercalation and 3D QSAR analysis of cis-2,4,5-trisubstituted-1,3-dithiolanes as a novel class of antitumor agents
چکیده انگلیسی

Acid-catalyzed transacetalation of dimethyl (2R,3S)-2,3-dimercapto-succinate and 1,1,3,3-tetramethoxypropane provided cis-4,5-dimethoxycarbonyl-2-(2′,2′-dimethoxyethyl)-1,3-dithiolane (2) in 77% yield. The esterification of 2 and l-amino acids provided 18 active antitumor cis-2-carbonylmethyl-4,5- di(l-aminoacyloxymethyl)-1,3-dithiolane analogs (5a–r). Five compounds (5b,c,e,k,p) exhibited remarkable antitumor activity in in vivo assays. The in vivo antitumor potency of 5e,k,p at 44.64 μmol/kg was similar to that of cytarabine at 89.28 μmol/kg. Several different assay systems, including UV–vis of CT DNA with or without the representative compound 5d and CD spectra of CT DNA with or without representative compounds 5b,f,i demonstrated that DNA is the target of 5a–r. A 3D QSAR model was established to elucidate quantitative relationships between in vivo antitumor activity and analog structures. An equation with r2 equal to 0.992 was built to predict antitumor activity of unknown cis-2,4,5-trisubstituted-1,3-dithiolane analogs.

cis-2-Carbonylmethyl-4,5-di(l-aminoacyloxymethyl)-1,3-dithiolane analogs (5a–r), and alignment stereoview of 5a–r reflecting tumor inhibition in mice.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 16, 15 August 2009, Pages 6085–6095
نویسندگان
, , , , , , , , ,