- Synthesis, antimicrobial and cytotoxic activities, and molecular docking studies of N-arylsulfonylindoles containing an aminoguanidine, a semicarbazide, and a thiosemicarbazide moiety
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Thirty-six N-arylsulfonyl-3-substituted indoles were designed and synthesized by combining the N-arylsulfonylindoles with aminoguanidine, semicarbazide, and thiosemicarbazide, respectively. Their antibacterial activities were screened, and cytotoxic activities were evaluated. The results showed that aminoguanidines (6) exhibited much better antibacterial activity than semicarbazides (7) and thiosemicarbazides (8). Most compounds in series 6 showed potent inhibitory activity against the tested bacterial strains, including multidrug-resistant strains, with MIC values in the range of 1.08–23.46 μM. The cytotoxic activity of the compounds 6c, 6d, 6h, 6j, 6k and 6l was assessed in two human cancer cell lines A590 and SGC7901, and one human normal cell line HEK 293T. The results indicated that compounds selected exhibited excellent activity against the tested cancer cells with IC50 values in the range of 1.51–15.12 μM suggesting the potential of them as new antibacterial and anticancer agents. What's more, the results of resistance study revealed that resistance of the tested bacteria toward 6d is not easily developed. Molecular docking studies revealed that the aminoguanidine and arylsulfonylindole moieties played a significant role in binding the target site of E. coli FabH-CoA receptor.
- Song, Mingxia,Wang, Shiben,Wang, Zengtao,Fu, Zhiyang,Zhou, Shengchao,Cheng, Huabin,Liang, Zhuo,Deng, Xianqing
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p. 108 - 118
(2019/01/28)
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- 2-Aminoimidazole-based antagonists of the 5-HT6 receptor – A new concept in aminergic GPCR ligand design
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A new strategy in the design of aminergic GPCR ligands is proposed – the use of aromatic, heterocyclic basic moieties in place of the evergreen piperazine or alicyclic and aliphatic amines. This hypothesis has been tested using a benchmark series of 5-HT6R antagonists obtained by coupling variously substituted 2-aminoimidazole moieties to the well established 1-benzenesulfonyl-1H-indoles, which served as the ligands cores. The crystallographic studies revealed that upon protonation, the 2-aminoimidazole fragment triggers a resonance driven conformational change leading to a form of higher affinity. This molecular switch may be responsible for the observed differences in 5-HT6R activity of the studied chemotypes with different amine-like fragments. Considering the multiple functionalization sites of the embedded guanidine fragment, diverse libraries were constructed, and the relationships between the structure and activity, metabolic stability, and solubility were established. Compounds from the N-(1H-imidazol-2-yl)acylamide chemotype (10a–z) exhibited high affinity for 5-HT6R and very high selectivity over 5-HT1A, 5-HT2A, 5-HT7 and D2 receptors (negligible binding), which was attributed to their very weak basicity. The lead compound in the series 4-methyl-5-[1-(naphthalene-1-sulfonyl)-1H-indol-3-yl]-1H-imidazol-2-amine (9i) was shown to reverse the cognitive impairment caused by the administration of scopolamine in rats indicating procognitive potential.
- Hogendorf, Adam S.,Hogendorf, Agata,Kurczab, Rafa?,Kalinowska-T?u?cik, Justyna,Popik, Piotr,Nikiforuk, Agnieszka,Krawczyk, Martyna,Sata?a, Grzegorz,Lenda, Tomasz,Knutelska, Joanna,Bugno, Ryszard,Staroń, Jakub,Pietru?, Wojciech,Mat?oka, Miko?aj,Dubiel, Krzysztof,Moszczyński-P?tkowski, Rafa?,Pieczykolan, Jerzy,Wieczorek, Maciej,Pilarski, Bogus?aw,Zajdel, Pawe?,Bojarski, Andrzej J.
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supporting information
p. 1 - 15
(2019/06/24)
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- Synthesis and quantitative structure-activity relationship (QSAR) study of novel N-arylsulfonyl-3-acylindole arylcarbonyl hydrazone derivatives as nematicidal agents
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In continuation of our program aimed at the discovery and development of natural-product-based pesticidal agents, 54 novel N-arylsulfonyl-3-acylindole arylcarbonyl hydrazone derivatives were prepared, and their structures were well characterized by 1
- Che, Zhiping,Zhang, Shaoyong,Shao, Yonghua,Fan, Lingling,Xu, Hui,Yu, Xiang,Zhi, Xiaoyan,Yao, Xiaojun,Zhang, Rui
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p. 5696 - 5705
(2013/07/26)
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- Antifungal agents. Part 5: Synthesis and antifungal activities of aminoguanidine derivatives of N-arylsulfonyl-3-acylindoles
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In order to discover more promising antifungal agents, a series of aminoguanidine derivatives of N-arylsulfonyl-3-acylindoles (5a-r) were prepared and evaluated in vitro for their antifungal activities against seven phytopathogenic fungi. Especially compo
- Xu, Hui,Wang, Yang-Yang
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scheme or table
p. 7274 - 7277
(2011/01/12)
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- Synthesis of Alkyl-Substituted N-Protected Indoles via Acylation and Reductive Deoxygenation
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The synthesis of 2-, 3-, and 5-alkyl-1-(phenylsulfonyl)indoles involving Friedel-Crafts acylation followed by reductive deoxygenation is described.The application of this acylation-deoxygenation sequence to 3-acyl-1-(phenylsulfonyl)indoles bearing potenti
- Ketcha, Daniel M.,Lieurance, Brett A.,Homan, Dominic F. J.,Gribble, Gordin W.
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p. 4350 - 4356
(2007/10/02)
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- A Convenient Synthesis of 3-Acylindoles via Friedel-Crafts Acylation of 1-(Phenylsulfonyl)indole. A New Route to Pyridocarbazole-5,11-quinones and Ellipticine
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A Friedel-Crafts acylation of 1-(phenylsulfonyl)indoles (1) with carboxylic acid anhydrides and acid chlorides in the presence of aluminum chloride gives 3-acyl-1-(phenylsulfonyl)indoles (2) in 81-99percent yields.Base hydrolysis converts 2 to 3-acylindoles (3) in 79-96percent yields.The reaction of 1-(phenylsulfonyl)indole (1a) with oxalyl chloride gives acid chloride 2h, which is converted to 3-cyanoindole (7) in three steps (75percent yield).Although a similar Friedel-Crafts alkylation of 1 was unsuccessful, in some cases the 3-acyl-1-(phenylsulfonyl)indoles 2a,e,f could be reduced to 3-alkyl-1-(phenylsulfonyl)indoles 8a,b,c in nearly quantitative yield with sodium borohydride in trifluoroacetic acid.The acid chloride derived from keto acid 9 did not cyclize to the desired pyridocarbazole-5,11-quinone 24 but rather to chloro keto lactam 10.However, acylation of 1a with acid chloride 22 followed by strong-base-mediated cyclization gives 24.Since quinone 24 has been previously converted to the alkaloid ellipticine 26, this route to 24 represents a new synthesis of ellipticine.Related synthetic schemes give rise to quinones 16 and 20.
- Ketcha, Daniel M.,Gribble, Gordon W.
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p. 5451 - 5457
(2007/10/02)
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