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Novel phenothiazine-dithiocarbamate analogues were designed by molecular hybridization strategy and synthesized and evaluated for their anticancer activity in vitro against three selected cancer cell lines (EC-109, MGC-803, and PC-3). The preliminary structure-activity relationship (SAR) for this phenothiazine-dithiocarbamate hybrids is explored. Among all analogues, 2-oxo-2-(10H-phenothiazin-10-yl)ethyl 4-ethylpiperazine-1-carbodithioate (8a) showed the most potent inhibitory activity with an [Formula: see text] value of [Formula: see text] against PC-3 cells. In addition, compound 8a could arrest the cell cycle at the G1 phase and regulate the expression of G1 checkpoint-related proteins, suggesting that phenothiazine-dithiocarbamate hybrids might be useful as cell cycle blockers.

The aim of this study was to research the effects of microRNA‐10a (miR‐10a) on synapse remodeling and neuronal cells in rats with Alzheimer's disease (AD) through BDNF‐TrkB signaling pathway. Rat models of AD were established. The neuronal cells were allocated into blank, negative control (NC), miR‐10a mimics, miR‐10a inhibitors, K252a, and miR‐10a inhibitors + K252a groups. Expressions of miR‐10a, p38, PSD95, BDNF, cAMP‐response element‐binding protein (CREB), and tropomyosin receptor kinase B (TrκB) were tested using RT‐qPCR and Western blotting. Neuron cell proliferation, cycle, and apoptosis were observed using Cell counting kit‐8 (CCK8) assay and flow cytometry. The ultrastructure was observed under a scanning electron microscope. The miR‐10a expression of AD rats increased while p38, PSD95, BDNF, CREB, and TrκB expression decreased compared with the normal rats. Dual luciferase reporter gene assay testified miR‐10a targeted BDNF. The expressions of p38, PSD95, BDNF, CREB, and TrκB decreased in the miR‐10a mimics and K252a groups. Compared with the blank and NC group, the miR‐10a mimics and K252a groups showed inhibited cell growth rate with cells mainly rest in the G1 satge, and increased spoptosis. The miR‐10a inhibitors group presented an opposite trend to the miR‐10a mimics and K252a groups. The synapse was complete and abundant in the miR‐10a inhibitors group while disappeared in the miR‐10a mimics and K252a groups. The results indicated that miR‐10a restrains synapse remodeling and neuronal cell proliferation while promoting apoptosis in AD rats via inhibiting BDNF‐TrkB signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract Structurally diverse trimethoxyphenyl-1,2,3-triazole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three cancer cell lines (PC3, MGC803 and HepG2). Among them, trimethoxyphenyl-1,2,3-triazole containing the coumarin fragement 19c displayed better antiproliferative activity results with IC50 values from 0.13 μM to 1.74 μM than anticancer drug colchicine. Compound 19c could inhibit MGC803 cell growth and colony formation, induce G2/M phase arrest by down expression of CDK1, and promote apoptosis by regulating DR5 and Bcl-2 family. Moreover, 19c strongly inhibited tubulin polymerization by interacting with the colchicine site. Graphical abstract Image 1 Highlights • Molecular diversity of trimethoxyphenyl-1,2,3-triazoles was explored. • 19c inhibited colony formation against MGC803 cells at 30 nM. • 19c arrested cell cycle at G2/M phase and induced apoptosis. • 19c was a novel colchicine site tubulin polymerization inhibitor. [ABSTRACT FROM AUTHOR]

With the expectation to find out new anti-gastric cancer agents with high efficacy and selectivity, a series of novel tertiary sulfonamide derivatives were synthesized and the anti-cancer activity was studied in three selected cancer cell lines (MGC-803, PC-3, MCF-7) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells and were more potent than the positive control (5-Fu). The structure-activity relationship of tertiary sulfonamide derivatives was explored in this report. Among the tested compounds, compound 13g containing benzimidazole moiety showed the best anti-proliferation activities against MGC-803 cells (IC 50 = 1.02 μM), HGC-27 cells (IC 50 = 1.61 μM), SGC-7901 (IC 50 = 2.30 μM) cells as well as the good selectivity between the cancer and normal cells. Cellular mechanism studies elucidated compound 13g inhibited the colony formation of gastric cancer cell lines. Meanwhile, compound 13g arrested cell cycle at G2/M phase and induced cell apoptosis. Mechanistically, compound 13g markedly decreased p-Akt and p- c -Raf expression, which revealed that compound 13g targeted gastric cancer cell lines via interfering with AKT/mTOR and RAS/Raf/MEK/ERK pathways. All the findings suggest that compound 13g might be a valuable lead compound for the anti-gastric cancer agents. Image 1 • Novel sulfonamide derivatives containing benzimidazole moiety were designed and prepared. • Compound 13g displayed excellent anti-proliferative activity and lower toxicity against the non-cancer cells. • Structure-activity relationship of sulfonamide derivatives was depicted. • Compound 13g caused cell cycle arrest at G2/M phase and induced cell apoptosis. • Compound 13g could down-regulate the p-Akt and p- c -Raf expression. [ABSTRACT FROM AUTHOR]