- A Diverse Range of Hemozoin Inhibiting Scaffolds Act on Plasmodium falciparum as Heme Complexes
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A diverse series of hemozoin-inhibiting quinolines, benzamides, triarylimidazoles, quinazolines, benzimidazoles, benzoxazoles, and benzothiazoles have been found to lead to exchangeable heme levels in cultured Plasmodium falciparum (NF54) that ranged over an order of magnitude at the IC50. Surprisingly, less active compounds often exhibited higher levels of exchangeable heme than more active ones. Quantities of intracellular inhibitor measured using the inoculum effect exhibited a linear correlation with exchangeable heme, suggesting formation of heme-inhibitor complexes in the parasite. In an effort to confirm this, the presence of a Br atom in one of the benzimidazole derivatives was exploited to image its distribution in the parasite using electron spectroscopic imaging of Br, an element not naturally abundant in cells. This showed that the compound colocalized with iron, consistent with its presence as a heme complex. Direct evidence for this complex was then obtained using confocal Raman microscopy. Exchangeable heme and inhibitor were found to increase with decreased rate of killing, suggesting that slow-acting compounds have more time to build up exchangeable heme complexes. Lastly, some but not all compounds evidently cause pro-oxidant effects because their activity could be attenuated with N-acetylcysteine and potentiated with t-butyl hydroperoxide. Collectively, these findings suggest that hemozoin inhibitors act as complexes with free heme, each with its own unique activity.
- Openshaw, Roxanne,Maepa, Keletso,Benjamin, Stefan J.,Wainwright, Lauren,Combrinck, Jill M.,Hunter, Roger,Egan, Timothy J.
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p. 362 - 376
(2021/02/01)
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- A 2 - (3 - aminophenyl) - benzothiazole derivatives and its preparation and use (by machine translation)
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The invention relates to the field of pharmaceutical chemistry, and in particular relates to a with anti-tumor activity of 2 - (3 - aminophenyl) - benzothiazole derivatives (formula I). Testing shows that the initial activity, the compounds of the inventi
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- Synthesis and biological evaluation of 2-(3-aminophenyl)-benzothiazoles as antiproliferative and apoptosis-inducing agents
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Abstract: A series of new 2-(3-aminophenyl)-benzothiazole derivatives were synthesized and evaluated for their in vitro antiproliferative activity against various human cancer cell lines including A549, HeLa, HepG2, MCF-7, MV4-11, and DB. Among the tested
- Cheng, Zhi-Qiang,Jiang, Cheng-Shi,Muehlmann, Luis Alexandre,Song, Jia-Li,Tao, Hong-Rui,Zhang, Hua,Zhang, Juan,Zhu, Kongkai
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p. 2093 - 2102
(2018/10/02)
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- Synthesis and structure-activity relationship of non-peptidic antagonists of neuropilin-1 receptor
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Neuropilins (NRPs) are VEGF-A165 co-receptors over-expressed in tumor cells, and considered as targets in angiogenic-related pathologies. We previously identified compound 1, the first non-peptidic antagonist of the VEGF-A165/NRP binding, which exhibits in vivo anti-angiogenic and anti-tumor activities. We report here the synthesis and biological evaluations of new antagonists structurally-related to compound 1. Among these molecules, 4a, 4c and 4d show cytotoxic effects on HUVEC and MDA-MB-31 cells, and antagonize VEGF-A165/NRP-1 binding. This study confirmed our key structure-activity relationships hypothesis and paved the way to compound 1 'hit to lead' optimization.
- Liu, Wang-Qing,Megale, Valentino,Borriello, Lucia,Leforban, Bertrand,Montes, Matthieu,Goldwaser, Elodie,Gresh, Nohad,Piquemal, Jean-Philip,Hadj-Slimane, Reda,Hermine, Olivier,Garbay, Christiane,Raynaud, Francoise,Lepelletier, Yves,Demange, Luc
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p. 4254 - 4259
(2014/09/29)
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- Synthesis and antibacterial evaluation of benzazoles tethered dihydro[1,3]oxazines
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Synthesis of various benzazoles tethered 1,3-oxazines such as 1H-benzo[d]azolophenyl-3,4-dihydro-2H-benzo- [e][1,3]oxazines 2a-j, 2-(3-(1H-benzo[d]oxazol-2-yl)phenyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine 3, 2-(3-(1Hbenzo-[ d]imidazol-2-yl)phenyl)-2,3
- Prasada, Davinder,Kumar Rohilla, Rajesh,Roy, Nilanjan,Nath, Mahendra
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body text
p. 739 - 745
(2012/07/01)
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- Thiophosphoryl-, thiophosphoryloxy-, and thiophosphorylamino-benzene derivatives as novel classes of hybrid pincer ligands
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The synthetic approaches to novel families of SCE (E = S',N,O) hybrid pincertype ligands bearing thophosphoryl, thiophosphoryloxy, and thiophosphorylamino groups in various combinations with thiophosphoryl-, thiocarbamoyl-, and imine- (including that of benzothiazole ring) donating functions have been developed. All of the ligands readily undergo direct cyclometallation (metal = Pd(II), Pt(II)) to afford 5,5- or 5,6-membered pincer complexes. Palladium complexes displayed from high to excellent catalytic performance in the Suzuki cross-coupling reaction of aryl bromides and phenylboronic acid and the higher asymmetry for a complex served as a factor of its higher catalytic activity. Copyright Taylor & Francis Group, LLC.
- Kozlov, Vladimir A.,Aleksanyan, Diana V.,Vasilev, Andrei A.,Odinets, Irina L.
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scheme or table
p. 626 - 637
(2011/06/22)
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- Hybrid thiophosphoryl-benzothiazole palladium SCN-pincer complexes: Synthesis and effect of structure modifications on catalytic performance in the suzuki cross-coupling
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The novel hybrid pincer-type ligands 3, 6, 9, and 11, bearing, as donating sites, a thiophosphoryl group and an imine moiety of the benzothiazole ring bound either directly to the central benzene core or attached to the latter one via O or NHlinkers, unde
- Kozlov, Vladimir A.,Aleksanyan, Diana V.,Nelyubina, Yulia V.,Lyssenko, Konstantin A.,Petrovskii, Pavel V.,Vasil'ev, Andrei A.,Odinets, Irina L.
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scheme or table
p. 2920 - 2932
(2011/07/31)
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- N-substituted 2′-(aminoaryl)benzothiazoles as kinase inhibitors: Hit identification and scaffold hopping
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Starting with a hit from vHTS attained by a docking procedure of virtual compounds into ATP pockets of different kinases applying the 4SCan technology, variations of the adenine mimic resulted in the identification of promising scaffolds, giving rise to in vitro IC50 values in the nanomolar range on different kinases down to 63 nM.
- Tasler, Stefan,Mueller, Oliver,Wieber, Tanja,Herz, Thomas,Krauss, Rolf,Totzke, Frank,Kubbutat, Michael H.G.,Schaechtele, Christoph
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body text
p. 1349 - 1356
(2009/11/30)
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- 2-arylbenzothiazole analogues and uses thereof
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The present invention relates to compounds of the general formula (I) and salts, prodrugs, and stereoisomers thereof, wherein Y independently represents S, O, NR2, SO, SO2; A independently represents a fife- or six-membered aromatic carbocycle or heterocycle and wherein R1 to R20 in formula (I) represent independently of each other a variety of different substituents comprising alkyl, aryl, aralkyl, alkylaryl, heteroaryl groups and monofunctional moieties.
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Page/Page column 16
(2008/06/13)
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- 2-Arylbenzothiazole analogues and uses thereof in the treatment of cancer
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The present invention relates to anticancer compounds of the general formula (I) and salts and physiologically functional derivatives thereof, wherein Y independently represents S, O, NR 2 , SO, SO 2 ; A independently represents a five- or six-membered aromatic carbocycle or heterocycle and wherein R 1 in formula (I) represents one of the heteroaryl groups defined in the claims.
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Page/Page column 28
(2010/11/25)
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- SUBSTITUTED HETEROARYL- AND PHENYLSULFAMOYL COMPOUNDS
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The present invention is directed at substituted heteroaryl- and phenylsulfamoyl compounds, pharmaceutical compositions containing such compounds and the use of such compounds as peroxisome proliferator activator receptor (PPAR) agonists. PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans. The compounds are also useful for the treatment of negative energy balance (NEB) and associated diseases in ruminants.
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Page/Page column 128
(2010/02/14)
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- Antitumor benzothiazoles. Part 2. Formation of 2,2'-diaminobiphenyls from the decomposition of 2-(4-azidophenyl)benzazoles in trifluoromethanesulfonic acid
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Decomposition of 2-(2-azidophenyl)- and 2-(3-azidophenyl)-benzothiazoles in trifluoromethanesulfonic acid generates ?-carbocations.These reactive intermediates have been trapped by triflate anion with the nucleophile substituting para to the original azido group to yield triflate-substituted arylamines. 2-(4-Azidophenyl)-benzothiazoles and -benzoxazoles behave differently: triflate-substituted arylamines are accompanied by symmetrical or unsymmetrical benzazolyl-substituted 2,2'-diaminobiphenyls as major products.These biphenyls have been identified by their characteristic 1H and 13C NMR spectra. 2,2'-Diaminobiphenyls are formed by initial C-C coupling interactions between the ?-carbocations and undecomposed 2-(4-azidophenyl)benzazoles and not by benzidine-type rearrangements as originally proposed.Symmetrical 2,2'-diaminobiphenyls have been oxidized by (diacetoxyiodo) benzene to give novel benzazolyl-substituted benzocinnolines.
- Stevens, Malcolm F. G.,Shi, Dong-Fang,Castro, Angeles
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- Solvatochromism and Prototropism in 2-(Aminophenyl)benzothiazoles
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The absorption and fluorescence spectra of 2-(2-aminophenyl)-, 2-(3-aminophenyl)-, and 2-(4-aminophenyl)benzothiazoles (o-APBT, m-APBT, and p-APBT, respectively) have been studied in different solvents and at various acid/base concentrations.The ultraviol
- Dey, Krishna Joy,Dogra, Sneh K.
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p. 3142 - 3152
(2007/10/02)
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