ABSTRACT
A series of novel benzimidazole and benzothiazole derivatives were designed and synthesized as inhibitors of SIRT1-SIRT3. The target compounds were synthesized from potassium O-ethyldithiocarbonate through a three-step route. The structures of the obtained compounds were elucidated by 1H NMR and HR-MS. Of all compounds, six showed potent SIRT2-inhibitory activities with IC50 values ranging from 2.8 to 21.2 μmol·L-1. Among them, compound 10c displayed the most potent SIRT2-inhibitory activities (IC50 = 2.8 μmol·L-1), with more than 35-fold selectivity over SIRT1 and SIRT3 (IC50>100 μmol·L-1).
ABSTRACT
<p><b>OBJECTIVE</b>In order to discuss the chemical foundation of hematopoietic effect of Siwu Tang, three fractions of different polarities (C1, C2 and C3) were prepared from Siwu Tang and the characteristics of these fractions' constituents were investigated.</p><p><b>METHOD</b>Fraction C1, C2 and C3 of Siwu Tang and corresponding fractions of Siwu Tang's four ingredient drugs were analyzed and compared, synthetically using the three methods of high-performance thin layer chromatography (HPTLC), high-performance liquid chromatography (HPLC) and direct infusion electrospray ionization mass spectrometry (ESI-MS).</p><p><b>RESULT</b>Fraction C1 of Siwu Tang contained various types of compounds, including ferulic acid, paeoniflorin and supposedly ligustilide, etc. Saccharide content in fraction C1 was very little. The major constituents in fraction C2 of Siwu Tang were paeoniflorin, monosaccaride and disaccharide. The major constituents in fraction C3 of Siwu Tang were monosaccaride and disaccharide.</p><p><b>CONCLUSION</b>With synthetical chromatographic and direct infusion ESI-MS methods, abundant information on composition of fractions of traditional Chinese medicine formulas can be obtained. The results gained with different methods can be compared with each other and corroborate each other, so that the obtained information can be more comprehensive and more definite than that gained with single method. The results of this study are important as references for the discussion of the chemical foundation of hematopoietic effect of Siwu Tang.</p>