Ergosterol peroxide (EP) has been extensively studied for its antitumor activities. However, its further development has been restricted due to its limited intracellular accumulation and poor aqueous solubility. In this study, a novel triphenylphosphonium cation (TPP+) moiety was coupled to ergosterol peroxide to precisely target it at tumor cell mitochondria. The synthesized Mito-EP derivatives Mito-EP-3a-3d displayed stronger cytotoxicity than the EP parent and exhibited selectively cytotoxic effects between cancer cells and normal gastric epithelial (GES-1) cells. The most potent compound, Mito-EP-3b, was 9.7-fold more efficacious than ergosterol peroxide in the MCF-7 (breast cancer) cell line and showed good selectivity (SI = IC50GES-1/IC50MCF-7 = 4.04, IC50: concentrations to inhibit 50% of cell growth). Furthermore, Mito-EP-3b was able to decrease the mitochondrial membrane potential and induced reactive oxygen species production, accompanied by activating the expression of cytochrome c and Bax, while Bcl-2 expression was suppressed. The molecular mechanism may refer to the mitochondrial apoptotic pathway. Overall, the above results incentivize the further study of Mito EP-3b derivatives as potent anticancer agents. (EP activities However solubility TPP+ TPP (TPP+ mitochondria MitoEP MitoEP3a3d MitoEPad 3a 3d d GES1 GES 1 (GES-1 compound MitoEP3b, MitoEP3b MitoEPb 3b, 3b b 9.7fold 97fold fold 9.7 9 7 MCF7 MCF MCF- breast SI IC50GES1/IC50MCF7 IC50GES1IC50MCF7 ICGESICMCF IC50GES 1/IC50MCF IC50MCF IC IC50GES-1/IC50MCF- 404 4 04 4.04 IC50 50 growth. growth . growth) Furthermore production Bax Bcl2 Bcl 2 Bcl- suppressed pathway Overall EP3b EPb agents (TPP (GES- 7fold 97 9. IC50GES1 IC50MCF7 IC50GES1/IC50MCF IC50GES1IC50MCF ICGES 1IC50MCF ICMCF IC50GES-1/IC50MCF 40 0 4.0 IC5 5 (GES 4.

A series of novel betulin-28-hydrazone derivatives (7a-7o) were synthesized. All compounds were evaluated for their in vitro cytotoxicities in four human carcinoma cells (HepG2, MCF-7, HCT-116 and A549). Among them, compound 7l displayed the most potent cytotoxicity with an IC50 (concentration of the tested compound that inhibits 50% of cell growth) value of 7.37 ± 0.38 μM against MCF-7 cells. The preliminary cellular mechanism studies indicated that compound 7l could induce MCF-7 cells apoptosis. The above findings indicated that compound 7l may be used as a lead compound for antitumor agents with improved efficacy.

A series of novel 2-(thiophen-2-yl)-4H-chromen-3-yl-sulfonate derivatives (4a-4n) were synthesized and investigated for their in vitro free radical scavenging potential as well as cytotoxic efficacies against selected cancer cell lines. The cytotoxicity of the 4H-chromene derivatives (4a-4n) was evaluated according to three human cancer cell lines (HepG2, A549, HeLa) by utilizing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Accordingly, part of the results exhibited better cytotoxic activities than that of the positive controls (4H-chromen-4-one and apigenin). Among them, compounds 4c-4g exhibited better training to the positive control against the three human cancer cell lines (half maximal inhibitory concentration (IC50) = 3.87 ± 0.12 to 21.38 ± 0.52 μM). Moreover, the extract of the 4H-chromene derivatives (4a-4n) showed better activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) in antioxidant assays compared to that of the positive control ascorbic acid (IC50 = 12.72 ± 0.27, 5.09 ± 0.21 μg mL−1). Thus, it can be confirmed from the bioassay results that the overall structural design, as well as proper substitution, is crucial in delivering anticipated biological effects. In this regard, spectroscopic techniques such as 1H nuclear magnetic resonance (NMR), 13C NMR, and high-resolution mass spectrometry (HRMS) were also carried out to confirm the final structures.

The effects of shot peening treatments on the microstructure and fatigue behavior of the teeth root in wet copper-based powder metallurgy friction plates were investigated and an efficient method for selecting optimal shot peening parameters for friction plates was proposed. Different experimental processes including microscopy observation, microhardness, roughness and X-ray diffraction measurements have been performed to characterize the treated surface of specimens. It is found that fatigue life of friction plates firstly increases and then decreases with the increase of Almen intensity, and the optimal fatigue life has improved over 55%. It is considered that both surface grain refinement and high residual compressive stress are the main ingredients responsible for the improved fatigue life. With further increase of Almen intensity, surface roughness of the teeth root gradually increases to a critical point, where rough peened surface may induce crack initiation due to stress concentration, and finally lead fatigue deteriorate.