•SAR for this 5,6-diaryl-1,2,4-triazine scaffold is explored.•11E inhibited colony formation and arrested cell cycle at G2/M phase.•11E caused morphological changes and decreased mitochondrial membrane potential.•5,6-Diaryl-1,2,4-triazine hybrids were discovered as novel apoptosis inducers.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.Download high-res image (263KB)Download full-size image

•A series of ormononetin-dithiocarbamate hybrids were discovered as novel antiproliferative inhibitors.•Structure-activity relationship for formononetin-dithiocarbamate scaffold.•Compound 8i inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways.A series of novel formononetin-dithiocarbamate derivatives were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell line (MGC-803, EC-109, PC-3). The first structure-activity relationship (SAR) for this formononetin-dithiocarbamate scaffold is explored in this report with evaluation of 14 variants of the structural class. Among these analogues, tert-butyl 4-(((3-((3-(4-methoxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)propyl)thio)carbonothioyl)piperazine-1-carboxylate (8i) showed the best inhibitory activity against PC-3 cells (IC50 = 1.97 μM). Cellular mechanism studies elucidated 8i arrests cell cycle at G1 phase and regulates the expression of G1 checkpoint-related proteins in concentration-dependent manners. Furthermore, 8i could inhibit cell growth via MAPK signaling pathway and inhibit migration via Wnt pathway in PC-3 cells.Download high-res image (171KB)Download full-size image

In continuation of our research aimed at the discovery and development of natural product-based antimicrobial and insecticidal agents, a series of 20 novel N-phenylpyrazole fraxinellone hybrid compounds were prepared and evaluated for their antibacterial and insecticidal activities. Two key steric configurations of compounds 4h and 4r were unambiguously determined by X-ray crystallography. Although only compound 4g showed better antibacterial activity against Bacillus subtilis with MIC value of 4 μg mL−1, than insecticidal activity, compounds 4n, 4o and 4t exhibited more promising insecticidal activity with final mortality rates (FMRs) of >60%, when compared with their precursor fraxinellone and the positive control toosendanin. This suggested that introducing polyhalogenated phenylpyrazole at C-4 and C-5 positions of fraxinellone could lead to more promising insecticidal derivatives than monohalogenated phenylpyrazole, especially introducing N-(2-chloro-4-fluoro-phenyl)pyrazole.

A series of novel coumarin derivatives were synthesized from commercially available chemical agents. All prepared compounds were evaluated for their in vitro antiproliferative activity against five selected human cancer cell lines (EC109, MGC-803, PC-3, MCF-7, and EC9706) and their in vitro antimicrobial activity against E. coli and M. albicans. 4-(3-Bromopropoxy)-2H-chromen-2-one exhibited the highest growth inhibition against MGC-803 cell line (IC50 47.7 μM) and 7-(2-bromoethoxy)-2H-chromen-2-one exhibited the highest growth inhibition against MCF-7 cell line (IC50 48.3 μM). The latter compound was also the most active against E. coli (MIC50 0.27 μg/ml).

Three novel hydroxylated tung oil (HTO) components with three conjugated double bonds were synthesized by aminolysis of tung oil with diethylolamine, and their cytotoxic effects on five human tumor cell lines were revealed for the first time. Compared with conjugated linolenic acid (CLnA) and conjugated linoleic acid (CLA) which have anti-cancer activity, the carboxyl-free HTO compounds also exhibited a cytotoxic effect against some tumor cell lines.

•LC–MS/MS was used for the determination of eight banned dyes in complex food.•A simple sample treatment procedure without further cleanup was developed.•Most of the analytes have satisfactory LODs and LOQs depending on matrices.A sensitive and accurate method based on the use of liquid chromatography–tandem mass spectrometry (LC–MS/MS) was developed for the simultaneous determination of eight illegal synthetic dyes (Sudan (I–IV), Para Red, Rhodamine B, Chrysoidin and Auramine O) in chili products. A simple sample treatment procedure entailing the use of an extraction step with acetonitrile/H2O (9/1) without further cleanup was developed. HPLC was performed on a C18 column using a multistep gradient elution with 5 mM ammonium acetate (pH 3.0 with formic acid) and methanol as the mobile phase. Mass spectral acquisition was done in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). Linear calibrations were obtained with correlation coefficients R2 > 0.99. Limit of detection (LOD) and limit of quantification (LOQ) for the studied dyes were in the ranges of 0.05–0.6 μg kg−1 and 0.3–3.0 μg kg−1 depending on matrices, respectively. The recoveries of the eight synthetic dyes in five matrices ranged from 70.5% to 119.2%. The intra- and inter-day precisions (RSDs) were between 2.3–15.8% and 5.7–15.6%, respectively. The applicability of the method to the determination of eight banned dyes in chili products was demonstrated.

Two benzophenone glucopyranosides have been isolated from the nut shell part of Mahkota Dewa. The structures were identified as 2,4′,6-trihydroxy-4-methoxy-benzophenone-2-O-β-d-glucoside (Mahkoside A) and 2,4′,6-trihydroxy-4-methoxy-6″-acetyl-benzophenone-2-O-β-d-glucoside (Mahkoside B). Mahkoside B was recognized as a novel compound. Furthermore, a series of benzophenone glucopyranoside derivatives (compounds 3–18) were synthesized and their bioactivities were characterized. Our results demonstrated that compound 18 has significant cytotoxicity against two esophageal cancer cell lines, stomach cancer cell line and prostate cancer cell line, with IC50 less than 10 μM, indicating its potential activity against cancer cells.Two benzophenone glucopyranosides have been isolated from the nut shell parts of Mahkota Dewa, identified as Mahkoside A and Mahkoside B. A series of benzophenone glucopyranoside derivatives (compounds 3–18) were synthesized. Compound 18 has significant cytotoxicity against four different cancer lines, with IC50 less than 10 μM/L.