- Synthesis, antimycobacterial and anticancer activity of novel indole-based thiosemicarbazones
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Based on the structural elements of bioactive indole-based compounds, a series of novel 1-substituted indole-3-carboxaldehyde thiosemicarbazones were synthesized as potential antimycobacterial and anticancer agents. The derivatives were prepared via a two
- Mashayekhi, Vida,Haj Mohammad Ebrahim Tehrani, Kamaleddin,Azerang, Parisa,Sardari, Soroush,Kobarfard, Farzad
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- Molecular dynamics guided development of indole based dual inhibitors of EGFR (T790M) and c-MET
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Secondary acquired mutation in EGFR, i.e. EGFR T790M and amplification of c-MET form the two key components of resistant NSCLC. Thus, previously published pharmacophore models of EGFR T790M and c-MET were utilized to screen an in-house database. On the ba
- Singh, Pankaj Kumar,Silakari, Om
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p. 163 - 170
(2018/05/22)
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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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- Identification of low micromolar dual inhibitors for aldose reductase (ALR2) and poly (ADP-ribose) polymerase (PARP-1) using structure based design approach
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Clinical studies have revealed that diabetic retinopathy is a multifactorial disorder. Moreover, studies also suggest that ALR2 and PARP-1 co-occur in retinal cells, making them appropriate targets for the treatment of diabetic retinopathy. To find the dual inhibitors of ALR2 and PARP-1, the structure based design was carried out in parallel for both the target proteins. A series of novel thiazolidine-2,4-dione (TZD) derivatives were therefore rationally designed, synthesized and their in vitro inhibitory activities against ALR2 and PARP-1 were evaluated. The experimental results showed that compounds 5b and 5f, with 2-chloro and 4-fluoro substitutions, showed biochemical activities in micromolar and submicromolar range (IC50 1.34–5.03?μM) against both the targeted enzymes. The structure-activity relationship elucidated for these novel inhibitors against both the enzymes provide new insight into the binding mode of the inhibitors to the active sites of enzymes. The positive results of the biochemical assay suggest that these compounds may be further optimized and utilized for the treatment of diabetic retinopathy.
- Chadha, Navriti,Silakari, Om
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supporting information
p. 2324 - 2330
(2017/05/09)
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- Containing α - methylene - γ - butyrolactone structure of indole compounds, preparation method and application thereof
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The invention discloses a novel indole compounds containing alpha-methylene-gamma-butyrolactone structures, a preparation method thereof and an application thereof serving as tubulin inhibitors in antitumor activity, and belongs to the field of medicinal
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Paragraph 0030; 0033; 0034
(2017/08/25)
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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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- Design, synthesis and anticancer activity of 4-morpholinothieno[3,2-d]- pyrimidine derivatives bearing arylmethylene hydrazine moiety
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Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a-f, 13a-k and 15a-h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC50 values of 0.003 μM, 0.42 μM and 0.74 μM, which was 1.6- to 290-fold more potent than GDC-0941.
- Zhu, Wufu,Zhai, Xin,Fu, Qiangqiang,Guo, Fei,Bai, Mei,Wang, Jianqiang,Wang, Haiyan,Gong, Ping
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experimental part
p. 1037 - 1045
(2012/10/08)
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- Design, synthesis and 3D-QSAR analysis of novel 2-hydrazinyl-4- morpholinothieno[3,2-d]pyrimidine derivatives as potential antitumor agents
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A series of 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and evaluated for their cytotoxic activities against five cancer cell lines. Most of them exhibited moderate to significant cytotoxic activities and high-selectivity against one or more cell lines, and nearly all of them had higher potency than positive controls against MDA-MB-231 cell line. The most promising compound 15f showed strong cytotoxic activities against H460, HT-29 and MDA-MB-231 cell lines, which were 1.7- to 66.5-folds more active than 2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)-1-piperazinyl)methyl)-4-(4- morpholinyl)thieno[3,2-d]pyrimidine(GDC-0941). To investigate the SARs of thieno[3,2-d]pyrimidine derivatives in more details, CoMFA (q2 = 0.436, r2 = 0.937) and CoMSIA (q2 = 0.706, r2 = 0.947) models on H460 cell line were established. The generated 3D-QSAR models can be used for further rational design of novel thienopyrimidines as highly potent and selective cytotoxic agents.
- Zhu, Wufu,Liu, Yajing,Zhai, Xin,Wang, Xiao,Zhu, Yan,Wu, Di,Zhou, Hongyu,Gong, Ping,Zhao, Yanfang
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p. 162 - 175
(2013/01/15)
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- Synthesis and biological evaluation of novel 6-hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-triazine derivatives as potential antitumor agents
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A series of 6-hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-triazine derivatives (5a-5l and 8a-8o) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for antiproliferative activity against three cancer cell lines (H460, HT-29, and MDA-MB-231). Several potent compounds were further evaluated against two other cell lines (U87MG, H1975). Most of the prepared compounds, particularly compounds 5c and 5j with IC50 values (0.07 and 0.05 μM, respectively) in the nM range, exhibited moderate to excellent antiproliferative activity and high selectivity against the H460 cancer cell line as compared with compound 1. The most promising compound 5j, possessing a cyano group at the 3-position of the benzene ring, showed strong antiproliferative activity against H460, HT-29, and MDA-MB-231 cell lines with IC50 values of 0.05, 6.31, and 6.50 μM, which were 4.6- to 190.4-fold more active than compound 1 (9.52, 29.24, and 36.21 μM), respectively. Copyright
- Zhu, Wufu,Liu, Yajing,Zhao, Yanfang,Wang, Haiyan,Tan, Li,Fan, Weijie,Gong, Ping
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p. 812 - 821,10
(2020/09/09)
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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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- Syntheses and in vitro antimycotic activities of 1-benzyl-3-(1-imidazolylmethyl)indoles
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Syntheses of seventeen 1-benzyl-3-(1-imidazolylmethyl)indoles with substituents at the benzyl moiety and at the indole C-2 position are described. The compounds were tested for their antifungal activities in vitro determination of the minimum inhibitory concentration (MIC). Three compounds exhibited appreciable activities against Cr. neoformans.
- Cavrini,Gatti,Roveri,Cesaroni,Mazzoni,Fiorentini
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p. 662 - 668
(2007/10/02)
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