- Design, synthesis and biological evaluation of N-substituted indole-thiazolidinedione analogues as potential pancreatic lipase inhibitors
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Pancreatic Lipase (PL) is a key enzyme responsible for the digestion of 50%–70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole-TZD hybrid analogues were synthesized, characterized and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole-3-carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Analogues 6d and 6e exerted potent PL inhibitory activity (IC50-6.19 and 8.96?μM, respectively). Further, these analogues exerted a competitive mode of PL inhibition. Moreover, molecular modelling studies were in agreement with the in vitro results (Pearson's r?=.8682, p?.05). The fluorescence spectroscopic analysis further supported the strong binding affinity of these analogues with PL. A molecular dynamics study (20?ns) indicated that these analogues were stable in a dynamic environment. Thus, the present study highlighted the potential role of indole-thiazolidinedione hybrid analogues as potential PL inhibitors and further optimization might result in the development of new PL inhibitory lead candidates.
- George, Ginson,Auti, Prashant S.,Paul, Atish T.
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- Synthesis, characterization, and biological evaluation of indole aldehydes containing N-benzyl moiety
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The present study describes the synthesis, characterization and biological evaluation of N-benzyl indole aldehydes. The biological activities of the newly synthesized compounds were examined by investigating their antioxidant and anti-inflammatory activities. The potential of these compounds as an antioxidant was determined by 2,2-diphenylpicrylhydrazyl, Nitric oxide, Superoxide, peroxide radical scavenging methods. We found that aldehydes 4a, 4b, 4c, and 4e and shows promising in vitro DPPH scavenging antioxidant activity while aldehyde 4b and 4e show good in vitro anti-inflammatory activity.
- Survase, Dattatray N.,Karhale, Shrikrishna S.,Khedkar, Vijay M.,Helavi, Vasant B.
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supporting information
p. 3486 - 3497
(2019/11/11)
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- Design, synthesis and biological evaluation of matrine derivatives as potential anticancer agents
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Using matrine (1) as the lead compound, a series of new 14-(N-substituted-2-pyrrolemethylene) matrine and 14-(N-substituted-indolemethylene) matrine derivatives was designed and synthesized for their potential application as anticancer agents. The structure of these compounds was characterized by 1H NMR, 13C NMR and ESI-MS spectral analyses. The target compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines (SMMC-7721, A549 and CNE2). The results revealed that compound A6 and B21 displayed the most significant anticancer activity against three cancer cell lines with IC50 values in range of 3.42–8.05 μM, which showed better activity than the parent compound (Matrine) and positive control Cisplatin. Furthermore, the Annexin V-FITC/PI dual staining assay revealed that compound A6 and B21 could significantly induce the apoptosis of SMMC-7721 and CNE2 cells in a dose-dependent manner. The cell cycle analysis also revealed that compound A6 could cause cell cycle arrest of SMMC-7721 and CNE2 cells at G2/M phase.
- Li, Zheng,Luo, Mengyang,Cai, Bin,Wu, Lichuan,Huang, Mengtian,Haroon-Ur-Rashid,Jiang, Jun,Wang, Lisheng
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supporting information
p. 677 - 683
(2018/02/06)
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- Ring-opened tetrahydro-γ-carbolines display cytotoxicity and selectivity with histone deacetylase isoforms
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This study is focused on modification of the indole moiety and the N1-zinc binding domain of tubastatin A, and the effects of such changes on biological activity. Fourteen N-substituted indoles (5–18) were synthesized and structure-activity relationship studies indicated that the change of the tetrahydro-γ-carboline in tubastatin A led to substituted indoles (compounds 7, 11, and 15) which showed significant improvements of selective inhibition for HDAC6 over HDAC1 and HDAC2 in comparison to ACY1215, a compound undergoing clinical trials. In addition, attachment of different hydroxamic acid groups, the zinc binding motif at the N1 position, contributes to the antiproliferative activity in cancer cells. Several synthetic compounds exhibited potent growth inhibition in a broad spectrum of tumor cell lines, induced irreversible growth arrest capacities by suppressing colony formation ability and activated the apoptosis pathway. The data provide compelling evidence that our newly synthesized compounds with type B to D hydroxamic acid groups as the zinc binding motif at the N1 position are potent selective inhibitors of HDAC6 and could be investigated preclinically as potential anticancer drugs.
- Nepali, Kunal,Lee, Hsueh-Yun,Lai, Mei-Jung,Ojha, Ritu,Wu, Tung-Yun,Wu, Gu-Xian,Chen, Mei-Chuan,Liou, Jing-Ping
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p. 115 - 127
(2016/12/30)
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- Selective and Efficient Formylation of Indoles (C3) and Pyrroles (C2) Using 2,4,6-Trichloro-1,3,5-Triazine/Dimethylformamide (TCT/DMF) Mixed Reagent
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This study introduces an efficient method for the selective formylation of indoles and pyrroles at the positions of C(3) and C(2), respectively. The mixture of three equivalents of N,N-dimethylformamide and one equivalent of 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) generates an easy handling formylating agent for the efficient formylation of these classes of compounds to give the corresponding aldehydes under mild reaction conditions. This procedure was highly efficient, and a range of formylated indoles and pyrroles were obtained in good to excellent yields.
- Iranpoor, Nasser,Panahi, Farhad,Erfan, Soodabeh,Roozbin, Fatemeh
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p. 904 - 910
(2017/03/27)
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- Design, synthesis and biological evaluation of a series of pyrano chalcone derivatives containing indole moiety as novel anti-tubulin agents
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A new series of pyrano chalcone derivatives containing indole moiety (3-42, 49a-49r) were synthesized and evaluated for their antiproliferative activities. Among all the compounds, compound 49b with a propionyloxy group at the 4-position of the left phenyl ring and N-methyl-5-indoly on the right ring displayed the most potent cytotoxic activity against all tested cancer cell lines including multidrug resistant phenotype, which inhibits cancer cell growth with IC50 values ranging from 0.22 to 1.80 μM. Furthermore, 49b significantly induced cell cycle arrest in G2/M phase and inhibited the polymerization of tubulin. Molecular docking analysis demonstrated the interaction of 49b at the colchicine binding site of tubulin. In experiments in vivo, 49b exerted potent anticancer activity in HepG2 human liver carcinoma in BALB/c nude mice. These results indicated these compounds are promising inhibitors of tubulin polymerization for the potential treatment of cancer.
- Wang, Guangcheng,Li, Chunyan,He, Lin,Lei, Kai,Wang, Fang,Pu, Yuzi,Yang, Zhuang,Cao, Dong,Ma, Liang,Chen, Jinying,Sang, Yun,Liang, Xiaolin,Xiang, Mingli,Peng, Aihua,Wei, Yuquan,Chen, Lijuan
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p. 2060 - 2079
(2014/04/17)
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- Synthesis and antimycobacterial activity of novel thiadiazolylhydrazones of 1-substituted indole-3-carboxaldehydes
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A series of novel thiocarbohydrazones of substituted indoles and their corresponding thiadiazole derivatives were prepared, and their structures were confirmed by different analytical and spectroscopic methods. The derivatives were prepared by a sequential synthetic strategy including substitution at N-1 position of indole ring by various aliphatic and benzylic substituents, followed by condensation with thiocarbohydrazide, and finally cyclization by triethyl orthoformate. The derivatives were tested for their antimycobacterial activity against Mycobacterium bovis BCG, and the results revealed that among the synthesized compounds, thiadiazole derivatives 4e, 4f, 4n, 4p, 4q, and 4t exhibited the highest activity with IC50 value of 3.91 μg/mL. The results indicate that the thiadiazole moiety plays a vital role in exerting antimycobacterial activity. A series of indole-based thiadiazole derivatives with various substitutions at N-1 position of indole ring have been synthesized and tested for their antimycobacterial activity. Compounds 4e (R = butyl), 4f (R = pentyl), 4n (R = 4-fluorobenzyl), 4p (R = 4-chlorobenzyl), 4q (R = 4-bromobenzyl) and 4t (R = 4-methoxybenzyl) were the most potent derivatives with IC50 value of 3.91 μg/mL.
- Haj Mohammad Ebrahim Tehrani, Kamaleddin,Mashayekhi, Vida,Azerang, Parisa,Sardari, Soroush,Kobarfard, Farzad,Rostamizadeh, Kobra
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p. 224 - 236
(2014/02/14)
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- Analogues and derivatives of oncrasin-1, a novel inhibitor of the C-terminal domain of RNA polymerase II and their antitumor activities
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To optimize the antitumor activity of oncrasin-1, a small molecule RNA polymerase II inhibitor, we evaluated 69 oncrasin-1 analogues for their cytotoxic activity against normal human epithelial cells and K-Ras mutant tumor cells. About 40 of those compoun
- Wu, Shuhong,Wang, Li,Guo, Wei,Liu, Xiaoying,Liu, Jinsong,Wei, Xiaoli,Fang, Bingliang
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experimental part
p. 2668 - 2679
(2011/06/27)
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- 3-(Azolylmethyl)-1H-indoles as selective P450 aromatase inhibitors
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The synthesis of 1-(halobenzyl) and 1-tosyl-3-(1H-imidazol-1-ylmethyl)-1H-indoles, 1-(halobenzyl) and 1-tosyl-3-(1H-1,2,4-triazol-1-ylmethyl)-1H-indoles and 1-(halobenzyl)-3-(4H-1,2,4-triazol-4-ylmethyl)-1H-indoles is described. 3-(Azolylmethyl)-1H-indoles were obtained in three steps from 1H-indole-3-carbaldehyde (1) by benzylation or tosylation, reduction and azole moiety fixation. In an alternative method, the bromo intermediates issued from the corresponding alcohols were condensed with the azolium sodium salts. Inhibitory activity against P450(arom) and P450(17α), and influence on retinoic acid metabolism were evaluated. Three imidazole compounds exhibited potent and selective aromatase inhibitory activity.
- Marchand,Le Borgne,Duflos,Robert-Piessard,Le Baut,Ahmadi,Hartmann,Palzer
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p. 211 - 218
(2007/10/03)
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- Synthesis and antimycobacterial activity of some indole derivatives of pyridine-2-carboxamidrazone and quinoline-2-carboxamidrazone
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A series of pyridine-2-carboxamidrazone and quinoline-2-carboxamidrazone derivatives containing the indole moiety was prepared. Some of the synthesized compounds showed an interesting in vitro antimycobacterial activity against a strain of Mycobacterium tuberculosis.
- Mamolo,Vio,Banfi
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