Discovery of 4-methoxy-N-(1-naphthyl)benzenesulfonamide derivatives as small molecule dual-target inhibitors of tubulin and signal transducer and activator of transcription 3 (STAT3) based on ABT-751

2区 · 化学

Article

作者: Meng, Fanxi ; Yue, Weixia ; Qian, Jinheng ; Wang, Xuebao ; Tu, Sijun ; Xie, Zixin ; He, Qin ; Tang, Haijie ; Lu, Ying ; Sun, Doudou ; Zuo, Zhigui ; Ye, Faqing ; Zhang, Yuan ; Chen, Huijun ; Lin, Humin ; Ma, Shumei

Overexpressed tubulin and continuously activated STAT3 play important roles in the development of many cancers and are potential therapeutic targets. A series of 4-methoxy-N -(1-naphthalene) benzenesulfonamide derivatives were designed and optimized based on β-tubulin inhibitor ABT-751 to verify whether STAT3 and tubulin dual target inhibitors have better antitumor effects. Compound DL14 showed strong inhibitory activity against A549, MDA-MB-231 and HCT-116 cells in vitro with IC₅₀ values of 1.35 μM, 2.85 μM and 3.04 μM, respectively. Further experiments showed that DL14 not only competitively bound to colchicine binding site to inhibit tubulin polymerization with IC₅₀ values 0.83 μM, but also directly bound to STAT3 protein to inhibit STAT3 phosphorylation with IC₅₀ value of 6.84 μM. Three other compounds (TG03, DL15, and DL16) also inhibit this phosphorylation. In terms of single target inhibition, DL14 is slightly inferior to positive drugs, but it shows a good anti-tumor effect in vivo, and can inhibit >80% of xenograft tumor growth. This study describes a novel 4-methoxy-N-(1-naphthyl) benzenesulfonamide skeleton as an effective double-targeted anticancer agent targeting STAT3 and tubulin.

2020-11-25·Zhen ci yan jiu = Acupuncture research

[Transcutaneous electrical acupoint stimulation relieves post-operative nausea and vomiting possibly by reducing serum motilin secretion in patients undergoing laparoscopic surgery].

Article

作者: Li, Jian-Li ; Wang, Xue-Jiao ; Rong, Jun-Fang

OBJECTIVE:

To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) of different acupoint combinations on postoperative nausea and vomiting (PONV) and serum motilin (MTL) content in patients undergoing laparoscopic surgery, so as to provide evidence for clinical selection of suitable acupoint compatibility.

METHODS:

A total of 140 patients undergoing elective laparoscopic surgery were randomly divided into general anesthesia (GA) control, TG₂ ［Neiguan (PC6) + Hegu (LI4)］, TG₃ ［PC6 + LI4 + Zusanli (ST36)］, and TG₄ ［PC6 + LI4 + ST36 + Sanyinjiao (SP6)］ groups, with 35 cases in each group. Patients of the TG₂, TG₃ and TG₄ groups received TEAS (2 Hz/100 Hz, 3-8 mA) of the above mentioned acupoint (bilateral) groups for 30 min before the induction of anesthesia until the end of the operation. Patients of the GA control group received intravenous injection of Midazolam, Sufentanil, Propofol, Rocuronium Bromide, etc. The blood sample (4 mL) from the right median cubital vein was collected at the time of patient's entry, 12 and 24 h after surgery, respectively, for measuring MTL concentration by enzyme-linked immunosorbent assay. The incidence of early and late PONV and changes of PONV degree within 24 h after surgery were recorded.

RESULTS:

The serum MTL concentrations were significantly decreased at 12 h after surgery in all the 4 groups (P<0.05), and decreased at 24 h after surgery in GA and TG2 groups vs their own pre-surgery (P < 0.05), and considerably higher at both 12 and 24 h after surgery in the TG₂, TG₃ and TG₄ groups than in the GA control group (P<0.05), and also evidently higher in the TG₃ and TG₄ groups than in the TG₂ group (P<0.05). The incidence of PONV was significantly lower in the TG₂, TG₃ and TG₄ groups than in the GA control group in the early and late periods (except TG₂ group) of surgery (P<0.05). The number of patients with PONV grade Ⅰ was significantly larger in the TG₂, TG₃ and TG₄ groups than in the GA control group at 24 h after surgery (P<0.05), suggesting a mild PONV in more patients undergoing TEAS.

CONCLUSION:

TEAS has a preventive effect on PONV in patients undergoing laparoscopic surgery, which may be related to its effect in reducing serum MTL concentration. The preventive effect of TEAS of PC6 + LI4 + ST36 and PC6 +LI4 + ST36 + SP6 is similar and better than TG₂ (two acupoints) group.

2020-01-01·International journal of medicinal mushrooms4区 · 生物学

Antibacterial Activity of Fruiting Body Extracts from Culinary-Medicinal Winter Mushroom, Flammulina velutipes (Agaricomycetes) against Oral Pathogen Streptococcus mutans

4区 · 生物学

Article

作者: Cui, Chen ; Cheng, Shujie ; Yang, Hua ; Wang, Rui ; Xiang, Yu ; Li, Bingxuan ; Xu, Hui ; Huang, Ruijie ; Zhou, Xuedong

The edible medicinal mushroom Flammulina velutipes (enokitake) has many applications as food and medicine, but its application in dentistry is unknown. This study aims to investigate the inhibitory effect of fruiting body extracts from F. velutipes on the growth and adhesion of Streptococcus mutans, the main cause of human caries, in vitro. Of the four extracts (named TG01 from water, TG02 from 95% ethanol, TG03 from 50% ethanol, and TG04 from ethyl acetate), TG03 had significant antibacterial activity (MIC = 10 mg/mL; MBC = 20 mg/mL). Planktonic growth and biofilm formation in S. mutans was repressed by TG03 at 5 mg/mL and above. Meanwhile, cytotoxicity analysis showed that TG03 was not toxic to human oral keratinocyte cells. HPLC-QQQ-MS analysis showed that the TG03 extract contained a large amount of arabitol, a sucrose substitute that reduces the development of caries. Thus, F. velutipes extracts can effectively inhibit the growth of the oral pathogen S. mutans without cytotoxicity against human oral keratinocytes. Therefore, F. velutipes is a good candidate for the development of oral hygiene agents to control dental caries.

100 项与 TG-03 相关的药物交易

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