Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. Two series of 1,5-diaryl substituted 1,2,3,4-tetrazoles were concisely synthesized, using a palladium-catalyzed cross-coupling reaction, and identified as potent antiproliferative agents and novel tubulin polymerization inhibitors that act at the colchicine site. SAR analysis indicated that compounds with a 4-ethoxyphenyl group at the N-1 or C-5 position of the 1,2,3,4-tetrazole ring exhibited maximal activity. Several of these compounds also had potent activity in inhibiting the growth of multidrug resistant cells overexpressing P-glycoprotein. Active compounds induced apoptosis through the mitochondrial pathway with activation of caspase-9 and caspase-3. Furthermore, compound 4l significantly reduced in vivo the growth of the HT-29 xenograft in a nude mouse model, suggesting that 4l is a promising new antimitotic agent with clinical potential.
In general, QOL in rural-urban female migrant workers was lower than Chinese female norms. Improving their job satisfaction and controlling job-related disease appears to be critical to improving their QOL.
A new series of tubulin polymerization inhibitors based on the 2-aryl/heteroaryl-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)thiazole scaffold was synthesized and evaluated for growth inhibition activity on a panel of cancer cell lines, cell cycle effects, and in vivo potency. Structure–activity relationships were elucidated with various substitutions at the 2-position of the thiazole skeleton. Hydrophobic moieties, such as phenyl and 3-thienyl, were well tolerated at this position, and variation of the phenyl substituents had remarkable effects on potency. The most active compound (3b) induced apoptosis through the mitochondrial pathway with activation of caspase-3. We also showed that it has potential antivascular activity since it reduced in vitro endothelial cell migration and disrupted capillary-like tube formation at noncytotoxic concentrations. Furthermore, compound 3b significantly reduced the growth of the HT-29 xenograft in a nude mouse model, suggesting that 3b is a promising new antimitotic agent with clinical potential.
BackgroundRural-to-urban female migrant workers have a lower quality of life compared to the general population. Improving these conditions remains highly challenging. This paper reports the health-related quality of life (HRQoL) of the female migrant workers in an educational project.MethodsIn this before-and-after study, a community-based health education intervention was developed to improve female migrant workers’ HRQoL and job satisfaction. A factory was selected as the location to implement the trial, using a before-and-after design. The education intervention included distribution and free access to study materials, monthly lectures, and counseling. The primary endpoint was HRQoL, and gynecological disease and job satisfaction were secondary endpoints. We assessed HRQoL at baseline and at 6-month follow-up using the Health Survey Short Form (SF-36).ResultsCompared to the baseline assessment, the participants at the 6-month survey reported higher General Health scores (standardized-β coefficients (Betas) of β = 0.056; P <0.001), Vitality scores (β = 0.066; P <0.001), Mental Health scores (β = 0.062; P <0.001), mental component summary scores (β = 0.040; P <0.001), and job satisfaction (Odds Ratio [OR] 2.104, 95% confidence interval [CI] 1.837-2.408; P <0.01).ConclusionsA community-based educational intervention, targeted at female migrant workers, appears effective in improving HRQoL and job satisfaction.
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