- 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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- PERFORIN INHIBITING BENZENESULFONAMIDE COMPOUNDS, PREPARATION AND USES THEREOF
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Compounds of formula (la) and pharmaceutically acceptable salts, solvates, and hydrates thereof and related methods of modulatin perforin activity on a cell: wherein Ring A is selected from a 6-10 membered aryl, 5-6 membered cycloalkyi, 5-6 membered heteroaryl or 5-6 membered heterocyclyl, wherein the heteroaryl and heterocyclyl rings comprise at least one heteroatom selected from N, O or S; and wherein the aryl, cycloalkyi, heteroaryl or heterocyclyl rings are optionally substituted with 1 to 3 substituents selected from halo, nitro, -C1-Cealkyl, -C1-Ceaminoalkyl, -C1-C6hydroxyalkyl, -haloC1-C6alkyl, -C1- C6alkoxyl, -haloC1-C6alkyl, -CH2OC(O)CrC6alkyl, -C(O)OC1,-C6alkyI, -NHC(O)C1,-C6alkyl, -NHS(O)2C1- C6alkyl, -S(O)2C1-C6alkyl, -S(O)2NH2, and -C(O)NJJ; Ring B is a 6-10 membered arylene or a 5-6 membered heteroarylene comprising at least one heteroatom selected from N, 0 or S; and wherein the aryl or heteroaryl is optionally, substituted with one or more substituents selected from -NJJ, -OJ, halo,C1 -C6alkyl, -haloC1- C6alkyl, -C1-C6alkoxy, -haloC1-C6alkoxyl, and -C(0)NJJ; Ring C is is selected from a 5-10 membered heteroarylene or a 5-10 membered heterocyclene, each comprising at least one heteroatom selected from N, S and O; Ring D is an optionally substituted benzofused 9-11 membered heterocyclyl or optionally substituted ben2ofused 9-11 membered heteroaryl comprising at least one heteroatom selected from N or O; L is a linker selected from branched and unbranched C1-C4 alkylene, -S(0)2-NH-, -C(0)-NH-, -NH-C(0)-NH-, -S(0)2-NH-C(0)-NH-, -S(0)2-NH-C(0) - and -CH=CH-; wherein Rings B and C, and Rings C and D, are connected to each other via a C-C bond at any of the available C atoms on each respective ring; and J in each occurrence is independently selected from H, optionally substituted C1-C6alkyl or optionally substituted haloC1-C6alkyl.
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Page/Page column 130
(2014/03/25)
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- Exploration of a series of 5-arylidene-2-thioxoimidazolidin-4-ones as inhibitors of the cytolytic protein perforin
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A series of novel 5-arylidene-2-thioxoimidazolidin-4-ones were investigated as inhibitors of the lymphocyte-expressed pore-forming protein perforin. Structure-activity relationships were explored through variation of an isoindolinone or 3,4-dihydroisoquinolinone subunit on a fixed 2-thioxoimidazolidin-4-one/thiophene core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perforin protein and perforin delivered in situ by natural killer cells was determined. A number of compounds showed excellent activity at concentrations that were nontoxic to the killer cells, and several were a significant improvement on previous classes of inhibitors, being substantially more potent and soluble. Representative examples showed rapid and reversible binding to immobilized mouse perforin at low concentrations (≤2.5 μM) by surface plasmon resonance and prevented formation of perforin pores in target cells despite effective target cell engagement, as determined by calcium influx studies. Mouse PK studies of two analogues showed T1/2 values of 1.1-1.2 h (dose of 5 mg/kg iv) and MTDs of 60-80 mg/kg (ip).
- Spicer, Julie A.,Lena, Gersande,Lyons, Dani M.,Huttunen, Kristiina M.,Miller, Christian K.,O'Connor, Patrick D.,Bull, Matthew,Helsby, Nuala,Jamieson, Stephen M. F.,Denny, William A.,Ciccone, Annette,Browne, Kylie A.,Lopez, Jamie A.,Rudd-Schmidt, Jesse,Voskoboinik, Ilia,Trapani, Joseph A.
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supporting information
p. 9542 - 9555
(2014/01/06)
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- An unusual and chemoselective reduction of ester grouping in nsubstituted-3-acetylindoles by sodium borohydride
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Treatment of 3-acetylindoles 1(a-e) with ethyl chloroacetate in the presence of K2CO3 and tetrabutylammoniumbromide (TBAB) as phase transfer catalyst in DMF, resulted in the formation of the corresponding N-substituted derivatives, e
- Venkatanarayana, Muvvala,Dubey, Pramod K.
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experimental part
p. 192 - 197
(2012/07/14)
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- Novel and simple methodology for the synthesis of 3-acetylindoles and their N-alkyl derivatives using TBAB as phase transfer catalyst
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Using 5% aq. NaOH, a simple method for the transformation of 3-cyanoacetylindoles 2(a-e) into 3-acetylindoles 3 (a-e), in good yields, is reported. Tetrabutylammoniumbromide (TBAB) is found to be an efficient phase transfer catalyst for the synthesis of N-alkyl derivatives 5(a-t) of 3-acetylindoles 3(a-e) giving products in excellent yields. 2 (a-e) were themselves obtained from simple indoles 1 (a-e) by reaction with cyano acetic acid in the presence of propionic anhydride at 100 °C for 5-10 min. Partial hydrolysis of 2 (a-e) under hot acidic conditions yielded the corresponding carboxamides α-(3-indolecarboxoyl)acetamides 4(a-e). Which could be readily transformed into the respective 3(a-e) by refluxing with 5% aq. NaOH for 2-2.5 h.
- Venkatanarayana,Dubey, Pramod K.
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experimental part
p. 656 - 662
(2012/06/01)
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- N-ARYLSULFONYL-3-SUBSTITUTED INDOLES HAVING SEROTONIN RECEPTOR AFFINITY, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITION CONTAINING THEM
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The present invention relates to novel N-arylsulfonyl-3-substituted indole compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their geometric forms, their N-oxides, their polymorphs, their pharmaceutically acceptable
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Page 44-45; 47
(2010/02/07)
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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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