- Design, synthesis and evaluation of XZH-5 analogues as STAT3 inhibitors
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Inhibition of the signaling pathways of signal transducer and activator of transcription 3 (STAT 3) has shown to be a promising strategy to combat cancer. In this paper we report the design, synthesis and evaluation of a novel class of small molecule inhibitors, that is, XZH-5 and its analogues, as promising leads for further development of STAT3 inhibitors. Preliminary SARs was established for XZH-5 and its derivatives; and the binding modes were predicted by molecular docking. Lead compounds with IC50 as low as 6.5 μM in breast cancer cell lines and 7.6 μM in pancreatic cancer cell lines were identified.
- Daka, Philias,Liu, Aiguo,Karunaratne, Chamini,Csatary, Erika,Williams, Cameron,Xiao, Hui,Lin, Jiayuh,Xu, Zhenghu,Page, Richard C.,Wang, Hong
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- Novel metal chelating molecules with anticancer activity. Striking effect of the imidazole substitution of the histidine-pyridine-histidine system
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Previously we have reported a metal chelating histidine-pyridine-histidine system possessing a trityl group on the histidine imidazole, namely HPH-2Trt, which induces apoptosis in human pancreatic adenocarcinoma AsPC-1 cells. Herein the influence of the imidazole substitution of HPH-2Trt was examined. Five related compounds, HPH-1Trt, HPH-2Bzl, HPH-1Bzl, HPH-2Me, and HPH-1Me were newly synthesized and screened for their activity against AsPC-1 and brain tumor cells U87 and U251. HPH-1Trt and HPH-2Trt were highly active among the tested HPH compounds. In vitro DNA cleavage assay showed both HPH-1Trt and HPH-2Trt completely disintegrate pUC19 DNA. The introduction of trityl group decisively potentiated the activity.
- Ali, Taha F.S.,Iwamaru, Kana,Ciftci, Halil Ibrahim,Koga, Ryoko,Matsumoto, Masahiro,Oba, Yasunori,Kurosaki, Hiromasa,Fujita, Mikako,Okamoto, Yoshinari,Umezawa, Kazuo,Nakao, Mitsuyoshi,Hide, Takuichiro,Makino, Keishi,Kuratsu, Jun-Ichi,Abdel-Aziz, Mohamed,Abuo-Rahma, Gamal El-Din A.A.,Beshr, Eman A.M.,Otsuka, Masami
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- NITROGEN-CONTAINING COMPOUND, METHOD FOR MANUFACTURING THE SAME, AND OPTICAL FUNCTIONAL MATERIAL INCLUDING THE SAME
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PROBLEM TO BE SOLVED: To provide a novel nitrogen-containing compound having luminescence property. SOLUTION: A nitrogen-containing compound represented by the following formula (I) in which RA, RB, R1, R2, R3, R4, and X are either one of the following (1) and (2). SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
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Paragraph 0085-0086
(2021/08/21)
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- NOVEL PYRROLO-LACTONE AND PYRROLE COMPOUNDS INDUCING CELLULAR GLUTATHIONE RECOVERY EFFECT AGAINST REACTIVE OXYGEN SPECIES, AND METHOD FOR PREPARING THE SAME
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The present invention provides: a novel pyrrolo-lactone compound, which can be used as an improved pain therapeutic agent containing various substituents by using glucose and ribose as reducing sugars and conducting a reaction with various kinds of natural and unnatural amino acids; and novel pyrrolo compounds produced during a process of manufacturing the same. The novel pyrrolo-lactone and pyrrole compounds are substances which can be used as improved pain therapeutic agent by having increased restoration ability of glutathione in living cells against reactive oxygen species.COPYRIGHT KIPO 2019
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Paragraph 0143; 0167-0171
(2019/05/10)
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- Histidine–dialkoxyanthracene dyad for selective and sensitive detection of mercury ions
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Histidine-dialkoxyanthracene (HDA) was synthesised as a turn off type fluorescent sensor for fast and sensitive detection of mercury ions (Hg2+) in aqueous media. The two histidine moieties act as ‘claws’ to selectively complex Hg2+. The binding ratio of HDA to Hg2+ was 1:1 (metal-to-ligand ratio). The association constant for Hg2+ towards the receptor HDA obtained from Benesi–Hildebrand plot was found to be 3.22?×?104?M?1 with detection limit as low as 4.7?nM (0.94?μg/L).
- Patil, Sachin,Belhajjame, Widad,Moosa, Basem,Khashab, Niveen M.
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p. 345 - 350
(2017/12/26)
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- Exciton-Coupled Circular Dichroism Characterization of Monotopically Binding Guests in Host?Guest Complexes with a Bis(zinc porphyrin) Tweezer
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A stiff-stilbene-linked bisporphyrin tweezer with inherent helicity was used for exciton-coupled circular dichroism (ECCD) characterization of a series of monotopically binding amine guest molecules. CD signals were observed for a variety of monoamines at relatively low tweezer/amine (host/guest) ratios between 1 : 10 to 1 : 70. For the amines producing the most intense CD signals, a binding stoichiometry of 1 : 2 was found. A likely explanation is the presence of guest-guest interactions in the complexes. This is supported by the correlation observed between CD signal intensity and magnitude of possible noncovalent binding between the guests, which can be divided into three groups showing no, moderate and strong response, respectively. Further support for this rationalization comes from molecular modelling.
- Olsson, Sandra,Sch?fer, Clara,Blom, Magnus,Gogoll, Adolf
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p. 1169 - 1178
(2019/01/04)
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- Discovery of a Membrane-Active, Ring-Modified Histidine Containing Ultrashort Amphiphilic Peptide That Exhibits Potent Inhibition of Cryptococcus neoformans
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The new structural classes of ultrashort peptides that exhibit potent microbicidal action have potential as future drugs. Herein, we report that C-2 arylated histidines containing tripeptides His(2-Ar)-Trp-His(2-Ar) exhibit potent antifungal activity against Cryptococcus neoformans with high selectivity. The most potent peptide 12f [His(2-biphenyl)-Trp-His(2-biphenyl)] displayed high in vitro activity against C. neoformans (IC50 = 0.35 μg/mL, MIC = MFC = 0.63 μg/mL) with a selectivity index of >28 and 2 times higher potency compared to amphotericin B. Peptide 12f exhibited proteolytic stability, with no apparent hemolytic activity. The mechanism of action study of 12f by confocal laser scanning microscopy and electron microscopy indicates nuclear fragmentation and membrane disruption of C. neoformans cells. Combinations of 12f with fluconazole and amphotericin B at subinhibitory concentration were synergistic against C. neoformans. This study suggests that 12f is a new structural class of amphiphilic peptide with rapid fungicidal activity caused by C. neoformans.
- Sharma, Krishna K.,Maurya, Indresh Kumar,Khan, Shabana I.,Jacob, Melissa R.,Kumar, Vinod,Tikoo, Kulbhushan,Jain, Rahul
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p. 6607 - 6621
(2017/08/17)
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- Unveiling and tackling guanidinium peptide coupling reagent side reactions towards the development of peptide-drug conjugates
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Peptide coupling reagents and especially uronium/guanidinium salts have been extensively utilized in solid-phase peptide synthesis. However, the impact of these reagents in solution phase synthesis, normally used in the formation of peptide-drug conjugates (PDCs), has not been fully explored. Herein, we identified that when guanidinium salts are used in classical peptide coupling conditions, besides leading to the formation of amide bonds, a uronium derivative can also be installed on specific amino acid scaffolds. The formation of this side product depends on the reaction conditions, as also on the nucleophilicity of the susceptible groups. Conditions to avoid this side product formation and a putative reaction mechanism describing its formation are reported.
- Vrettos, Eirinaios I.,Sayyad, Nisar,Mavrogiannaki, Eftychia M.,Stylos, Evgenios,Kostagianni, Androniki D.,Papas, Serafim,Mavromoustakos, Thomas,Theodorou, Vassiliki,Tzakos, Andreas G.
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p. 50519 - 50526
(2017/11/10)
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- Rational design of a highly selective fluorescent sensor for l-histidine detection in aqueous solution
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Computational studies in combination with experimental research were used to design a new rapid, selective and sensitive "turn-on" fluorescent sensor (H3) for l-histidine, which can be first quenched by Ni2+ and then recovered upon addition of His.
- Qiao, Yan,Chen, Bin,Yang, Yangyang,Wang, Xin,Xu, Yufang,Li, Honglin
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supporting information
p. 1310 - 1314
(2016/02/03)
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- SILOXANE POLYMERS WITH A CENTRAL POLYSILOXANE POLYMER BLOCK WITH TERMINAL ORGANOFUNCTIONAL RADICALS COMPRISING UREA AND/OR CARBAMATE GROUPS AND AMINO ACID RADICALS
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The invention relates to siloxane polymer comprising a central polysiloxane polymer block B with organofunctional radicals, which are terminal or bonded laterally on the polymer block, comprising IPDI and amino acid derivatives which are covalently bonded via a hydrophobic or hydrophilic linker group Q1′, Q2′, and to compositions comprising these siloxanes. Furthermore, processes for their preparation and their use are disclosed.
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Page/Page column
(2015/02/05)
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- Cysteine as a sustainable sulfur reagent for the protecting-group-free synthesis of sulfur-containing amino acids: Biomimetic synthesis of l-ergothioneine in water
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Biomass-derived cysteine was used as a sustainable sulfur source for the synthesis of rare sulfur-containing amino acids, such as l-ergothioneine (4), which might be a new vitamin, and various l- or d-2-thiohistidine compounds. Key in this simple, one-pot two-step procedure in water is a bromine-induced regioselective introduction of cysteine followed by a novel thermal cleavage reaction in the presence of thiols, a safer alternative to hazardous red phosphorus. Besides avoiding hazardous sulfur reagents, the new protecting-group-free approach reduces drastically the total number of steps, compared to described procedures. The main drawback, i.e. handling of liquid bromine as an activating and oxidizing reagent in water, was addressed by evaluating four alternative methods using in situ generation of bromine or HOBr, and first encouraging results are described.
- Erdelmeier, Irene,Daunay, Sylvain,Lebel, Remi,Farescour, Laurence,Yadan, Jean-Claude
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supporting information; scheme or table
p. 2256 - 2265
(2012/09/08)
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- Structure-stability correlations for imine formation in aqueous solution
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Imine formation between 25 aldehydes and 13 amines in aqueous solution in the pH range 7-11 was studied by 1H NMR spectroscopy. A three-parameter linear equation correlating logarithms of imine formation constants with pKa and HOMO energies of amines and LUMO energies of aldehydes is proposed. In view of the widespread occurrence of imine-forming processes in both chemistry and biology, the data presented are of significance for physical organic chemistry and of particular interest for dynamic combinatorial chemistry. Copyright
- Godoy-Alcantar,Yatsimirsky, Anatoly K.,Lehn
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p. 979 - 985
(2007/10/03)
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- Functionalized derivatives of hyaluronic acid, formation of hydrogels in situ using same, and methods for making and using same
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Methods for chemical modification of hyaluronic acid, formation of amine or aldehyde functionalized hyaluronic acid, and the cross-linking thereof to form hydrogels are provided. Functionalized hyaluronic acid hydrogels of this invention can be polymerized in situ, are biodegradable, and can serve as a tissue adhesive, a tissue separator, a drug delivery system, a matrix for cell cultures, and a temporary scaffold for tissue regeneration.
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- N-benzoyl amino acids as LFA-1/ICAM inhibitors 1: Amino acid structure-activity relationship
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The association of ICAM-1 with LFA-1 plays a critical role in several autoimmune diseases. N-2-Bromobenzoyl L-tryptophan, compound 1, was identified as an inhibitor to the formation of the LFA-1/ICAM complex. The SAR of the amino acid indicates that the carboxylic acid is required for inhibition and that L-histidine is the most favored amino acid.
- Burdick, Daniel J.,Paris, Ken,Weese, Kenneth,Stanley, Mark,Beresini, Maureen,Clark, Kevin,McDowell, Robert S.,Marsters Jr., James C.,Gadek, Thomas R.
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p. 1015 - 1018
(2007/10/03)
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- Synthesis and evaluation of deglycobleomycin A2 analogues containing a tertiary N-methyl amide and simple ester replacement for the L-histidine secondary amide: Direct functional characterization of the requirement for secondary amide metal complexation
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The synthesis and comparative examination of 3-5, analogues of deglycobleomycin A2 (2) which address the inferred importance of the L-histidine secondary amide directly, are detailed. The agent 3 lacks only the L-histidine β-hydroxy group of deglycobleomycin A2 and the corresponding agents 4 and 5 incorporate a tertiary N-methyl amide and simple ester in place of the L-histidine secondary amide. The DNA cleavage properties of 3 proved essentially indistinguishable from those of deglycobleomycin A2 (2) confirming that the distinctions between bleomycin A2 (1) and deglycobleomycin (2) are due to the removal of the disaccharide and not the introduction of the L-histidine free β-hydroxy group. The agents 4 and 5 containing a tertiary N-methyl amide and ester in place of the L-histidine secondary amide were found to cleave duplex DNA but to do so in a nonsequence selective fashion with a substantially reduced efficiency and a diminished double to single strand cleavage ratio that are only slightly greater than that of free iron itself. These latter observations establish the functional requirement for the L-histidine secondary amide and are consistent with the proposals that the L-histidine deprotonated secondary amide is required for functional metal chelation and activity.
- Boger, Dale L.,Teramoto, Shuji,Cai, Hui
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p. 179 - 193
(2007/10/03)
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- Synthesis of potent inhibitors of histidinol dehydrogenase
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Novel inhibitors of histidinol dehydrogenase are described. The most potent inhibitors, compounds 18 (K(i)* = 4.4 nM) and 19 (K(i)* = 2.9 nM) exploit a hitherto unreported lipophilic binding pocket adjoining the active site. Preliminary SAR data for this pocket are detailed. The electrophilic ketone 6 designed to bind to an active site nucleophile was a considerably weaker inhibitor (IC50 ~ 20 μM).
- Dancer, Jane E.,Ford, Mark J.,Hamilton, Kenneth,Kilkelly, Michael,Lindell, Stephen D.,O'Mahony, Mary J.,Saville-Stones, Elizabeth A.
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p. 2131 - 2136
(2007/10/03)
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- Five-membered ring systems with bonded imidazolyl ring substituents
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A class of 5-membered heterocyclic compounds having at least one heteroatom, substituted on the heterocyclic ring by an imidazolyl moiety, are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal or dependence; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; movement disorders; and presenile and senile dementia.
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- 4,5,6,7-TETRAHYDRO-1H-IMIDAZO(4,5-C)PYRIDINE-6-CARBOXYLIC ACID ANALOGS HAVING ANTIHYPERTENSIVE ACTIVITY
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This invention relates to novel substituted derivatives of 4,5, 6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid and analogs thereof, which are useful for the treatment of hypertension, as well as, novel pharmaceutical compositions and methods of use.
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