6125-31-1Relevant articles and documents
Novel thienopyrimidine-aminothiazole hybrids: Design, synthesis, antimicrobial screening, anticancer activity, effects on cell cycle profile, caspase-3 mediated apoptosis and VEGFR-2 inhibition
El-Dash, Yara,Elzayat, Emad,Abdou, Amr M.,Hassan, Rasha A.
, (2021/07/10)
A series of novel hybrid compounds of hexahydrobenzo[4,5]thieno[2,3-d]pyrimidine with aminothiazole scaffolds were synthesized. The synthesized compounds were evaluated for their cytotoxic activity against the NCI-60 human tumor cell line panel. Compounds 7c, 7d and 7e exhibited significant antiproliferative activities at 10?5 M dose. Compound 7c exhibited excellent cytotoxic activity against CNS cancer cell lines including SNB-75 and SF-295 as well as renal cancer cell line CAKI-1 when compared with sorafenib as standard anticancer drug. In addition, compound 7d showed almost comparable anticancer activity to sorafenib against SNB-75 cell line and displayed moderate activity against SF-295 and CAKI-1 cell lines in comparison to sorafenib. Compound 7c inhibited the vascular endothelial growth factor receptor 2 (VEGFR-2) with IC50 of 62.48 ± 3.7 nM and decreased both total VEGFR-2 and phosphorylated VEGFR-2 in treated SNB-75 cells suggesting its ability to down regulate cell proliferation, growth, and survival. The flow cytometric analysis showed that 7c displayed its cytotoxic activity through the reduction of the cellular proliferation and induction of cell cycle arrest at the G2/M phase. Compound 7c clearly boosted the level of the apoptotic caspase-3. All the synthesized compounds were also screened for their antibacterial and antifungal activity against four pathogenic strains of both Gram-positive and Gram-negative as well as Candida albicans. Only compound 7d exhibited antifungal activity against Candida albicans compared to nystatin as the standard antifungal compound.
Synthesis, biological evaluation, and docking studies of novel 5,6-diaryl-1,2,4-triazine thiazole derivatives as a new class of α-glucosidase inhibitors
Wang, Guangcheng,Peng, Zhiyun,Gong, Zipeng,Li, Yongjun
, p. 195 - 200 (2018/04/02)
A novel 5,6-diaryl-1,2,4-triazine thiazole derivatives (7a-7q) were synthesized and characterized by 1H NMR and 13C NMR and evaluated for their α-glucosidase inhibitory activity. All tested compounds displayed good α-glucosidase inhibitory activity with IC50 values ranging between 2.85 ± 0.13 and 14.19 ± 0.23 μM when compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μM). Compound 7i (IC50 = 2.85 ± 0.13 μM) exhibited the highest activity among this series of compounds. Molecular docking studies were carried out in order to investigate the binding mode of this class of compounds to α-glucosidase. This study showed that these 5,6-diaryl-1,2,4-triazine thiazole derivatives are a new class of α-glucosidase inhibitors.
Design and discovery of novel thiazole derivatives as potential MMP inhibitors to protect against acute lung injury in sepsis rats: Via attenuation of inflammation and apoptotic oxidative stress
Ge, Lingqing,Hu, Qiaozhen,Shi, Mengrao,Yang, Huiyun,Zhu, Guoji
, p. 32909 - 32922 (2017/07/10)
Acute lung injury (ALI) is considered to be an inflammatory syndrome of the airway system that is initiated by failure of the respiratory system. In this study, we evaluated the possible benefits of some novel thiazole derivatives against ALI. These derivatives were synthesised and evaluated for the inhibition of MMP-8 and MMP-2. Most of the tested compounds had better inhibitory activity for MMP-8 than for MMP-2, with compound 26 being the most potent analogue among the tested series. Thus, compound 26 was further investigated to determine its beneficial effects in an ALI model of rats with sepsis. In vivo results suggested that compound 26 significantly reduced the protein concentration together with a decline in enhanced leukocytes compared with those in ALI induced by cecal ligation and puncture. The effect of compound 26 on myeloperoxidase activity was also quantified, which was found to be significantly reduced at the maximum tested dose of 20 mg kg-1. The protective effect of compound 26 against ALI was also established to occur via the significant modulation of various biomarkers; for example, the malondialdehyde level was found to be reduced, while there were increased levels of superoxide dismutase and glutathione. Thus, it is proposed that compound 26 exerts a protective effect against ALI via modulation of the antioxidant status. Furthermore, the compounds tested caused significant attenuation of the levels of tumour necrosis factor-α, interleukin-1β, and interleukin-6, and protected the lung through the modulation of systemic inflammatory mediators in septic rats. In conclusion, we identified a novel series of thiazoles, which potentially exert protective effects against ALI via the inhibition of numerous pathways.
