- Synthesis and Biological Evaluation of Indole-2-carbohydrazide Derivatives as Anticancer Agents with Anti-angiogenic and Antiproliferative Activities
-
A novel series of indole-2-carbohydrazide derivatives were synthesized, characterized, and evaluated for their antiproliferative activities against two cancer cell lines, HCT116 and SW480, and a normal human fetal lung fibroblast cell line, MRC-5. Among this series, compound 24 f displayed potent cytotoxic activities in vitro against HCT116 and SW480 cell lines with GI50 values of 8.1 and 7.9 μm, respectively, and was inactive against MRC-5 cells. The newly synthesized compounds were also evaluated for anti-angiogenesis capabilities by chick chorioallantoic membrane, human umbilical vein endothelial cell (HUVEC) migration, and endothelial microtubule formation assays. Moreover, the effects of 24 f on the vascular endothelial growth factor receptor-2 and the signaling pathway in HUVECs indicated that this compound inhibits VEGFR-2 and its downstream related proteins. These results indicate that compound 24 f, as well as the other derivatives, are promising inhibitors of angiogenesis.
- Zhang, Jianqiang,Liu, Tongyang,Chen, Mei,Liu, Feifei,Liu, Xingyuan,Zhang, Jihong,Lin, Jun,Jin, Yi
-
-
Read Online
- Design and synthesis of novel 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivatives as antiproliferative EGFR and BRAFV600E dual inhibitors
-
Recent studies have shown additive and synergistic effects associated with the combination of kinase inhibitors. BRAFV600E and EGFR are attractive targets for many diseases treatments and have been studied extensively. In keeping with our interest in developing anticancer targeting EGFR and BRAFV600E, a novel series of 2,3-dihydropyrazino[1,2-a]indole-1,4-dione has been rationally designed, synthesized and evaluated for their antiproliferative activity against a panel of four human cancer cell lines. Compounds 20–23, 28–31, and 33 showed promising antiproliferative activities. These compounds were further tested for their inhibitory potencies against EGFR and BRAFV600E kinases with erlotinib as a reference drug. Compounds 23 and 33 exhibited equipotency to doxorubicin against the four cell lines and efficiently inhibited both EGFR (IC50 = 0.08 and 0.09 μM, respectively) and BRAFV600E (IC50 = 0.1 and 0.29 μM, respectively). In cell cycle study of MCF-7 cell line, compounds 23 and 33 induced apoptosis and exhibited cell cycle arrest in both Pre-G1 and G2/M phases. Molecular docking analyses revealed that the new compounds can fit snugly into the active sites of EGFR, and BRAFV600E kinases. Compound 23, 31 and 33 adopted similar binding orientations and interactions to those of erlotinib and vemurafenib.
- Abdelrahman, Mostafa H.,Abdu-Allah, Hajjaj H. M.,Abou-Ghadir, Ola F.,Al-Wahaibi, Lamya H.,Ali, Asmaa T.,Farghaly, Hatem S.,Gouda, Ahmed M.,Salem, Ola I. A.,Trembleau, Laurent,Youssif, Bahaa G. M.
-
-
- Preparation method of indole-2-formic acid derivative
-
The invention discloses a preparation method of an indole-2-formic acid derivative, wherein the preparation method comprises the steps: by using an oxazolone compound as a raw material, carrying out areaction in an organic solvent at the temperature of 70-150 DEG C under the action of alcohol, alkali and a catalyst, tracking by TLC until the raw material is completely reacted, and separating andpurifying the obtained reaction solution to obtain the indole-2-formic acid derivative. The technology is adopted, the target product indole-2-formic acid derivative is prepared by taking an oxazolonecompound as a raw material through one-pot reaction under the action of alcohol, alkali and a catalyst, so that direct conversion from an oxazolone ring to an indole ring is realized, reaction stepsand an intermediate process are reduced, and the method has the characteristics of cheap raw materials, environmental friendliness and the like, and is suitable for industrial production.
- -
-
Paragraph 0046-0048
(2020/07/14)
-
- Synthesis, and evaluation of in vitro and in vivo anticancer activity of 14-substituted oridonin analogs: A novel and potent cell cycle arrest and apoptosis inducer through the p53-MDM2 pathway
-
A series of novel oridonin derivatives bearing various substituents on the 14-OH position were designed and synthesised. Their antitumour activity was evaluated in vitro against three human cancer cell lines (HCT116, BEL7402, and MCF7). Most tested derivatives showed improved anti-proliferative activity compared to the lead compound oridonin and the positive control drug 5-fluorouracil (5-Fu). Among them, compound C7 (IC50 = 0.16 μM) exhibited the most potent anti-proliferative activity against HCT116 cells; it was about 43- and 155-fold more efficacious than that of oridonin (IC50 = 6.84 μM) and 5-Fu (IC50 = 24.80 μM) in HCT116 cancer cells. Interestingly, the IC50 value of compound C7 in L02 normal cells was 23.6-fold higher than that in HCT116 cells; it exhibited better selective anti-proliferative activity and specificity than oridonin and 5-Fu. Furthermore, compound C7 possibly induced cell cycle arrest and apoptosis by regulating the p53-MDM2 signalling pathway. Notably, C7 displayed more significant suppression of tumour growth than oridonin in colon tumour xenograft models where the tumour growth inhibition rate was 85.82%. Therefore, compound C7 could be a potential lead compound for the development of a novel antitumour agent.
- Shen, Qing-Kun,Deng, Hao,Wang, Shi-Ben,Tian, Yu-Shun,Quan, Zhen-Shan
-
-
- ANTIBACTERIAL COMPOUNDS
-
The present application provides compounds of formula: Methods of using these compounds for killing bacterial growth and treating bacterial infections are also provided.
- -
-
Page/Page column 86-89
(2019/11/04)
-
- En Route to 2-(Cyclobuten-1-yl)-3-(trifluoromethyl)-1H-indole
-
A six-step synthetic route from 4-chloro-2-methylaniline to 5-chloro-2-(cyclobut-1-en-1-yl)-3-(trifluoromethyl)-1H-indole (1) has been reported. Compound 1a is a key impurity of reverse transcriptase inhibitor efavirenz, an important anti-HIV/AIDS drug. Synthetic challenges, dead ends, and detours are discussed.
- Gazvoda, Martin,Krivec, Marko,?asar, Zdenko,Ko?mrlj, Janez
-
p. 2486 - 2493
(2018/02/23)
-
- Facile synthesis of indolelactones using Mn(III)-based oxidative substitution-cyclization reaction
-
Based on the oxidation of indole with Mn(OAc)3 in the presence of 1,1-diarylethenes affording 3-vinyl-substituted indoles, a similar oxidation using indole-2-carboxylic acids was evaluated in order to effectively introduce the substituent group to the C-3 position of the indolecarboxylic acids. The coupling reaction followed by oxidative cyclization smoothly proceeded at room temperature in an AcOH-HCO2H mixed solvent to give the desired indolelactones in high yields. The reaction details, the structure determination of the products and a brief reaction mechanism are described.
- Inoue, Takeshi,Nishino, Hiroshi
-
p. 431 - 450
(2019/07/31)
-
- Design, synthesis and pharmacophoric model building of new 3-alkoxymethyl/3-phenyl indole-2-carboxamides with potential antiproliferative activity
-
Novel 3-alkoxymethyl/3-phenyl indole-2-carboxamide derivatives were synthesized and evaluated for their anticancer activity. Most of the tested compounds showed moderate to excellent activity against the tested cell lines (MCF7 and HCT116). 3-Phenyl substitution on indole with p-piperidinyl phenethyl 24a and p-dimethylamino phenethyl 24c exhibited anticancer activity against MCF7 with IC50 of 0.13 and 0.14?μm, respectively. Further mechanistic study of the most active compounds through their action on cell cycle showed disturbance in cell cycle progression and cell cycle arrest. For future development of this series of compounds, pharmacophore study was conducted which indicated that the enhancement of the activity could be achieved through the addition of acceptor or donating groups to the already-present indole nucleus.
- Abdelrahman, Mostafa H.,Aboraia, Ahmed S.,Youssif, Bahaa G. M.,Elsadek, Bakheet E. M.
-
-
- Substituted indole - 2 - formic acid (by machine translation)
-
This invention relates to a substituted indole - 2 - carboxylic acid synthesis method, is to replace the phenyl hydrazine hydrochloride or arylhydrazines as raw materials, through with pyruvic acid ethyl ester cheng zong, Fischer indole synthesis by reaction of substituted indole - 2 - carboxylic acid ethyl ester, hydrolysis to obtain the substituted - 2 - carboxylic acid. Product purity is greater than 97%, the reaction yield is 64%. Synthesis method of the invention with non-harsh conditions, the operation is simple, and environmental friendliness, it has certain economic benefits. It is a kind of raw materials are easy, simple operation, three wastes, high yield of indole - 2 - carboxylic acid synthesis method. (by machine translation)
- -
-
Paragraph 0045; 0048
(2017/10/28)
-
- Synthesis of 3,3-Dihalo-2-oxindoles from 2-Substituted Indoles via Halogenation–Decarboxylation/Desulfonamidation–Oxidation Process
-
A novel one-pot reaction which combines halogenation, decarboxylation/desulfonamidation with oxidation has been developed. Diverse valuable 3,3-dihalo-2-oxindole compounds can be produced rapidly and safely with isolated yields of up to 98% under mild conditions. (Figure presented.).
- Jiang, Xiaojian,Zhang, Feng,Yang, Junjie,Yu, Pei,Yi, Peng,Sun, Yewei,Wang, Yuqiang
-
supporting information
p. 3938 - 3942
(2016/12/30)
-
- Synthesis and anti-tumor activity of 2-amino-3-cyano-6-(1H-indol-3-yl)-4- phenylpyridine derivatives in vitro
-
A series of novel 2-amino-3-cyano-6-(1H-indol-3-yl)-4-phenylpyridine derivatives were synthesized and their cytotoxic activity against A549, H460, HT-29 and SMMC-7721 cell lines was evaluated in vitro. Among them, ten compounds (10, 11, 14, 16, 17, 26, 27, 29, 30 and 31) displayed excellent anti-tumor activity against different cell lines. The most promising compound 27 showed strong anti-tumor activity against A549, H460, HT-29 and SMMC-7721 cell lines with IC50 values of 22, 0.23, 0.65 and 0.77 nM, which were 2.6-, 83-, 1.1 × 103- and 2.0 × 103- fold more active than MX-58151 (IC50 values of 0.058, 0.019, 0.70 and 1.53 μM), respectively.
- Zhang, Fan,Zhao, Yanfang,Sun, Li,Ding, Lu,Gu, Yucheng,Gong, Ping
-
experimental part
p. 3149 - 3157
(2011/06/26)
-
- Antidiabetic agents
-
A compound of the formula wherein n, m, Z, R1, R5, R8, R9, R10 and R11 are as defined above, useful in the treatment of diabetes, insulin resistance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, cataracts, hyperglycemia, hypercholesterolemia, hypertension, hyperinsulinemia, hyperlipidemia, atherosclerosis, and tissue ischemia, particularly myocardial ischemia.
- -
-
-
