Design, synthesis and of antitumor activity study of coumarinderivatives bearing benzothiazole or benzene moiety / 药学学报

Based on coumarin core structure as the procaspase-3 activator 1541 from our previous study, twelve coumarin derivatives bearing benzothiazole or benzene moiety were designed and synthesized. Target compounds were evaluated for in vitro antitumor activity against a procaspase-3 overexpressing cancer cell line (human histiocytic lymphoma cell, U937) and a procaspase-3 no-expression cancer cell line (human breast adenocarcinoma cell, MCF-7) to rule out off-target effects. The results revealed that coumarin derivatives bearing benzothiazole showed more potent inhibition activity and selectivity against procaspase-3 over-expressing cancer cell line (U937) than procaspase-3 low-sensitive cancer cell line (MCF-7). Caspase-3 activity evaluation showed that coumarin derivatives bearing benzothiazole showed remarkable caspase-3 activation activity, among them, compound 5f displayed the strongest activity with 93% degree. Flow cytometric assay revealed that compound 5f could inhibit proliferation of tumor cells by inducing apoptosis. Procaspase-3 activity assay showed that compound 5f showed strong procaspase-3 activation activity.

Research on anti-tumour activity of 2-( N-propylamine)-6-trifluoromethoxy-benzothiazoIe / 中国药理学通报

Aim To study the anti-tumour activity and mechanism of 2-( N-propylamine )-6-trifluoromethoxy-benzothiazole. Methods The anti-proliferative activities against HeLa, HepG2, MCF-7 and SP2/0 cancer cell lines were assessed by CCK-8 assay. The morphological changes of cancer cells were observed by Ho-echst staining. Effects on the cell migration were evaluated by monolayer cells wound healing assay. The cell apoptosis analysis was evaluated by using the flow cytometric analysis. Results Compound 2-(N-propylamine)-6-trifluoromethoxy-benzothiazole showed good selectivity and inhibitory effects against four tumor cell lines. Especially, the effects on MCF-7 cells were very significant. This compound could inhibit the migration of MCF-7 cells and induce early apoptosis. Conclusions 2-(N-propylamine)-6-trifluoromethoxy-benzothi-azole can inhibit the proliferation of four tumor cell lines. It shows inhibitory effects on MCF-7 cells by inducing early apoptosis.

N-Myristoyltransferases as antileishmanial targets: a piggyback approach with benzoheterocyclic analogues

Leishmaniasis is one of the neglected diseases that remain in need for pharmacological alternatives. In this context, N-Myristoyltransferases (NMT) arise as interesting targets to explore since they are involved in the co/post-translational processing of peptides which are responsible for host cell invasion. Studies that consider these enzymes as targets point out the potential of benzoheterocyclic compounds as inhibitors of Candida albicans's N-myristoyltransferase. Here we applied a combination of comparative binding site analysis and molecular docking studies based on a Piggyback approach in the search for new Leishmania major NMT ligands. Our results revealed that NMT enzymes from both pathogens present enough structural similarity to allow extrapolation of the knowledge available from C. albicans studies to develop new L. major NMT inhibitors. Molecular docking studies with benzoheterocyclic analogues indicate the potential of benzothiazole derivatives as L. major NMT ligands, giving rise to a completely new class of chemical compounds to be explored in the development of antileishmanial drugs.

Synthesis of benzimidazole and benzothiazole derivatives as a sirtuins 2 inhibitor / 药学学报

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).

Research on the mechanism of benzothiazole derivative BD960 on T cell proliferation / 医学研究生学报

Objective Benzothiazole derivative BD960 has immunosuppressive activity after cell -based assays for high-throughput screening.The paper aimed to investigate the involved mechanism of BD960 on T cell proliferation. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads.Then the T cells were activated by anti-CD3/anti-CD28 mAbs or alloantigen.The effect of BD960 on activa-ted T cell proliferation, the cytotoxic effect BD960 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometer.Cytokine levels, including IL-2, IL-4, IL-6, IL-10, IL-17A and IFN-γ, were determined by ELISA. Results BD960 significantly inhibited the proliferation of T cells stimulated by anti-CD3/anti-CD28 mAb or alloantigen in a dose-dependent manner.The IC50 value is (2.3 ±0.3)μmol/L or (2.5 ±0.3)μmol/L, respectively.Moreover, BD960 had no obvious cytotoxic effects on rest-ing T cells and peripheral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .The ratio of CD25 expression on T cell was 69.7%after stimulated by Anti-CD3/CD28 mAbs with 72 h, the concentration (0.625、2.5、10)μmol/L of BD960 also had no potent effects on the ratio, but 0.1μmol/L FK506 could inhibit CD25 expression as low as 9.4%.The G0/G1 phase of activated T cells was 58.5%after stimulated by BD960 with 96 h.BD960 could induce cell cycle arrest at the G0/G1 phase in activated T cells with the increase of concentration and RAPA in the concentration of 0.1 μmol/L was 91.5%.In addition, BD960 (0.625、2.5、10)μmol/L could inhibit the secretion of IFN-γ, IL-6 and IL-17 in activated T cells with the increase of concentration, without any effects on the secretion of IL-2, IL-4 and IL-10. Conclusion BD960 not only exerts the inhibition on the late stage of T cell activation of cell proliferation but also inhibits the secretion of inflammatory cytokines, such as IL-6, IL-17 and IFN-γ, while the mechanism of BD960 on T cell proliferation was not the same as FK506.As a result, BD960 has the potential to be the lead compound to develop a new immunosuppressant.

Inhibitory effect of small molecule compound BD691 on activated T cell proliferation and its mechanism / 医学研究生学报

Obej ctive Abnormal proliferation of T cells plays an important role in the development of autoimmune diseases. The article aimed to study the inhibitory effect of small molecule compound BD691 on T cell proliferation and its mechanism. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads,then T cells were ac-tivated with anti-CD3/CD28 mAbs or alloantigen.The inhibitory effect of BD691 on activated T cell proliferation, the cytotoxic effect BD891 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometry.Furthermore, ELISA was used to detect the secretion of cytokines associated with T cell differentiation. Results BD691 significantly inhibited the prolif-eration of T cells being stimulated by anti-CD3/CD28 mAb or alloantigen in a dose-dependent manner, and IC50 values are (8.5 ± 1.5)μmol/L and (7.2 ±1.3)μmol/L, respectively.However, BD691 had no obvious cytotoxic effects on resting T cells and periph-eral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .In T cells which were not activated by anti-CD3/CD28 mAb, the percentage of CD25+T cells is only 1.6%of the total cells, while the number increased to 68% after activating treatment.Mean-while, in T cells which were activated by 0, 3.3, 10, 30μmol/L BD691, no obvious change of CD25 expression were observed, while immunosuppressant FK506 (0.1μmol/L) significantly decreased the expression of CD25 +T cells (14.9%).In unactivated T cells, 95.6%cells were at G0/G1 phase, while after activation, the percentage of cells at G0/G1 phase reduced to 57.7%.In addition, BD691 inhibited the secretion of IFN-γ, IL-6 and IL-17 in activated T cells, but had no effects on the secretion of IL-2, IL-4 and IL-10. Co nclusion BD691 exerts no effects on T cell activation, but it inhibits T cell proliferation by inducing T cell cycling arrest at G0/G1 phase.Moreover, BD691 inhibits the secretion of key cytokines (such as IFN-γ, IL-6, IL-17) closely related to the differ-entiation of Th1 and Th17 cells.The results suggest that BD 691 is a potential lead compound to develop a new immunosuppressant for the inhibition of abnormal proliferation and differentiation of T cells.

Synthesis, Characterization and evaluation of Anti-inflammatory and Analgesic activity of Benzothiazole derivatives.

A parent benzothiazole nucleus was synthesized by para amino acetanilide, then it is subjected to treatment with various substituted aromatic aldehydes to get the corresponding Schiff’s bases followed by treatment with pthalic anhydride to form 2-(6- acetamidobenzo[d]thiazol-2-ylcarbamoyl)benzoic acid. The structures of synthesized compounds were confirmed by various spectroscopic methods such as IR, 1H NMR and mass spectroscopy. The products were evaluated for their anti-inflammatory and analgesic activities. Some of the compounds exhibited potent activities when compared with the standards.

Synthesis, characterization and biological evaluations of some 5-(substituted amino alkyl)-2-{(1, 3- benzothiazole-2-yl)}-thiazolidine-4 one Mannich bases as potent antibacterial agents.

Novel Mannich bases of 5-(substituted amino alkyl)-2-{(1, 3 benzothiazole-2-yl)}-thiazolidine-4 one, are synthesized by amination at 5th position of thiazolidine ring of 2-{(1, 3 benzothiazole-2-yl)}-thiazolidine-4 one using formaldehyde and various secondary amines. The synthesized compounds have been characterized by physico-chemical and spectral analysis and screened for their in- vitro antibacterial activity against various strains of bacteria.