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Novel chalcone-dithiocarbamate hybrids were designed, synthesized and evaluated for antiproliferative activity against selected cancer cell lines (MGC803, MCF7, and PC3). Among these analogues, (E)-2-oxo-2-((4-(3-(3,4,5-trimethoxyphenyl)acryloyl)phenyl)amino)ethyl-4-(2-hydroxyethyl)piperazine-1-carbodithioate (12d) showed the best inhibitory activity against PC3 cells (IC 50  = 1.05 μM). Cellular mechanism studies elucidated 12d could inhibit colony formation, arrest cell cycle at G2/M phase and induce DNA damage against PC3 cells. Compound 12d also induced mitochondrial apoptosis by caspase activation, MMP decrease, ROS production and catalase (CAT) inhibition. Importantly, 12d inhibited epithelial-mesenchymal transition (EMT) process by regulating EMT-related proteins (E-cadherin, N-cadherin, Vimentin, MMP2, MMP9). These results indicated that 12d is a promising lead compound and deserves further investigation for prevention and treatment of human prostate cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A series of 5,6-diaryl-1,2,4-triazines hybrids bearing a 1,2,3-triazole linker were synthesized by molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, EC-109 and PC-3). The first structure-activity relationship (SAR) for these 5,6-diaryl-1,2,4-triazines is explored in this report with evaluation of 15 variants of the structural class. Among these chemical derivatives, 3-(((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5,6-diphenyl-1,2,4-triazine (11E) showed the more potent inhibitory effect against three cell lines than 5-Fu. Cellular mechanism studies in MGC-803 cells elucidated 11E inhibited colony formation and arrested cell cycle at G2/M phase. Furthermore, compound 11E caused morphological changes, decreased mitochondrial membrane potential, and induced apoptosis through the apoptosis-related proteins in MGC-803 cells. It was the first time, to our knowledge, that 5,6-diaryl-1,2,4-triazines bearing a 1,2,3-triazole linker were used as potential apoptosis inducers., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aim: To detect the inhibitor of apoptosis protein Livin in non-small cell lung cancer patients with perioperative serum levels were analyzed trends in perioperative period to explore the Livin in non-small cell lung cancer diagnosis, classification and prognosis of clinical significance., Methods: Enzyme-linked immunosorbent assay (ELISA) of 40 patients with non-small cell lung cancer patients before surgery, the serum levels of Livin expression and 20 cases of normal healthy human serum levels of Livin were detected., Results: Non-small cell lung cancer patients was significantly higher than the level of serum Livin healthy control group. Before surgery (median 526.49 ng/L, quartile 357.93-825.57 ng/L), postoperative (median 286.49 ng/L, quartile 157.93-515.57 ng/L), there was significant difference between the two groups (P<0.05).Livin the average level of serum with non-small cell lung cancer the relationship between pathology: I, II period (median 326.49 ng/L, quartile 201.54-623.19 ng/L) and stage III (median 586.31 ng/L, quartile 411.79-965.34 ng/L) statistically significant difference between (P<0.05); tumor lymph node metastasis in 11 cases (median 562.03 ng/L, quartile 382.64-982.61 ng/L) and the 29 cases without lymph node metastasis (median 344.59 ng/L, quartile 167.27-646.20 ng/L) significant difference between (P<0.05); organization credits of: high, medium, poorly differentiated among the three groups without significant differences (P>0.05)., Conclusion: Livin as a new inhibitor of apoptosis protein in non-small cell lung cancer diagnosis, staging has some clinical value.

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.

A series of 5,6-diaryl-1,2,4-triazines hybrids bearing a 1,2,3-triazole linker were synthesized by molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, EC-109 and PC-3). The first structure-activity relationship (SAR) for these 5,6-diaryl-1,2,4-triazines is explored in this report with evaluation of 15 variants of the structural class. Among these chemical derivatives, 3-(((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5,6-diphenyl-1,2,4-triazine (11E) showed the more potent inhibitory effect against three cell lines than 5-Fu. Cellular mechanism studies in MGC-803 cells elucidated 11E inhibited colony formation and arrested cell cycle at G2/M phase. Furthermore, compound 11E caused morphological changes, decreased mitochondrial membrane potential, and induced apoptosis through the apoptosis-related proteins in MGC-803 cells. It was the first time, to our knowledge, that 5,6-diaryl-1,2,4-triazines bearing a 1,2,3-triazole linker were used as potential apoptosis inducers.

A series of novel dithiocarbamate–chalcone derivates were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell lines (EC-109, SK-N-SH and MGC-803). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds II2 and II5 exhibited the excellent growth inhibition against SK-N-SH with IC 50 values of 2.03 μM and 2.46 μM, respectively. Further mechanism studies revealed that compound II2 could obviously inhibit the proliferation of SK-N-SH cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase. [ABSTRACT FROM AUTHOR]

• V7 exhibited the potent antiproliferative activity against MGC803 cells. • V7 induced cell cycle G2/M phase arrest. • V7 induced apoptosis against MGC803 cells. • V7 inhibited NEDDylation and MAPK pathways. A series of novel indole derivatives were synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (MGC803, EC-109 and PC-3). Among these analogues, 2-(5-methoxy-1 H -indol-1-yl)- N -(4-methoxybenzyl)- N -(3,4,5-trimethoxyphenyl)acetamide (V7) showed the best inhibitory activity against MGC803 cells with an IC 50 value of 1.59 μM. Cellular mechanisms elucidated that V7 inhibited colony formation, induced apoptosis and arrested cell cycle at G2/M phase. Importantly, indole analogue V7 inhibited NEDDylation pathway and MAPK pathway against MGC803 cells. [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]