- New Anti-Seizure (Arylalkyl)azole Derivatives: Synthesis, In Vivo and In Silico Studies
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(Arylalkyl)azoles are a class of antiepileptic compounds including nafimidone, denzimol, and loreclezole (LRZ). Nafimidone and denzimol are thought to inhibit voltage-gated sodium channels (VGSCs) and enhance γ-aminobutyric acid (GABA)-mediated response. LRZ, a positive allosteric modulator of A-type GABA receptors (GABAARs), was reported to be sensitive to Asn265 of the β2/β3 subunit. Here, we report new N-[1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethylidene]hydroxylamine esters showing anticonvulsant activity in animal models, including the 6-Hz psychomotor seizure test, a model for therapy-resistant partial seizure. We performed molecular docking studies for our active compounds using GABAAR and VGSC homology models. They predicted high affinity to the benzodiazepine binding site of GABAAR in line with the experimental results. Also, the binding mode and interactions of LRZ in its putative allosteric binding site of GABAAR is elucidated.
- Sari, Suat,Dalkara, Sevim,Kaynak, Filiz Betül,Reynisson, Jóhannes,Sara?, Selma,Karakurt, Arzu
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- Imidazolylacetophenone oxime-based multifunctional neuroprotective agents: Discovery and structure-activity relationships
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Alzheimer's disease (AD) possesses a complex pathogenetic mechanism. Nowadays, multitarget agents are considered to have potential in effectively treating AD via triggering molecules in functionally complementary pathways at the same time. Here, based on the screening (~1400 compounds) against neuroinflammation, an imidazolylacetophenone oxime ether (IOE) was discovered as a novel hit. In order to obtain SARs, a series of imidazolylacetophenone oxime derivatives were constructed, and their C=N bonds were confirmed as the Z configuration by single crystals. These derivatives exhibited potential multifunctional neuroprotective effects including anti-neuroin?ammatory, antioxidative damage, metal-chelating, inhibition of acetylcholinesterase (AChE) properties. Among these derivatives, compound 12i displayed the most potent inhibitory activity against nitric oxide (NO) production with EC50 value of 0.57 μM 12i can dose-dependently suppress the expression of iNOS and COX-2 but not change the expression of HO-1 protein. Moreover, 12i exhibited evidently neuroprotective effects on H2O2-induced PC12 cells damage and ferroptosis without cytotoxicity at 10 μM, as well as selectively metal chelating properties via chelating Cu2+. In addition, 12i showed a mixed-type inhibitory effect on AChE in vitro. The structure-activity relationships (SARs) analysis indicated that dioxolane groups on benzene ring and rigid oxime ester can improve the activity. Parallel artificial membrane permeation assay (PAMPA) also verified that 12i can overcome the blood-brain barrier (BBB). Overall, this is the ?rst report on imidazolylacetophenone oxime-based multifunctional neuroprotective effects, suggesting that this type of compounds might be novel multifunctional agents against AD.
- Ren, Bo,Guo, Cong,Liu, Run-Ze,Bian, Zhao-Yuan,Liu, Rong-Chun,Huang, Lan-Fang,Tang, Jiang-Jiang
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- Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies
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In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.
- Zhou, You,Lu, Xin,Du, Chenxi,Liu, Yijun,Wang, Yifan,Hong, Kwon Ho,Chen, Yao,Sun, Haopeng
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- BuChE-IDO1 inhibitor as well as preparation method and application thereof
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The invention relates to the field of medicines, and particularly discloses a BuChE-IDO1 inhibitor as well as a preparation method and application thereof. The 7-chlorine-3-substituted benzothiophene part of sertaconazole is chemically modified, the influence of the 7-chlorine-3-substituted benzothiophene part of sertaconazole on the in-vitro inhibitory activity of AChE, BuChE and IDO1 is explored, the target compound is further optimized, and the technical problems that an existing BuChE-IDO1 inhibitor is poor in pertinence and safety are solved. What is explored is that an appropriate substituent group introduced to a 2-benzothiazole ring can form additional interaction with surrounding amino acids and heme iron, so that the binding affinity of the analogue with BuChE and IDO1 is increased, and a new idea is broadened for more efficient and targeted treatment of advanced AD diseases.
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Paragraph 0070-0072; 0100-0101
(2021/04/26)
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- One pot synthesis of α-N-heteroaryl ketone derivatives from aryl ketones using aqueous NaICl2
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A simple and efficient method for the synthesis of α-heteroaryl ketones from aryl ketones and amine using aqueous sodium dichloroiodate is established. This method is mild, operationally simple, has a short reaction time, and easy workup procedure to afford the corresponding α-N-heteroaryl ketone derivatives in moderate to good yield.
- Ghodse, Shrikant M.,Hatvate, Navnath T.,Telvekar, Vikas N.
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supporting information
(2021/12/08)
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- Diaryl-containing imidazole compound and preparation method and medical application thereof
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The invention discloses a diaryl-containing imidazole compound. The invention further discloses application of the diaryl-containing imidazole compound to preparation of drugs for preventing or treating Alzheimer's disease. The inventor screens butyrylcholine esterase and IDO1 as carriers for inhibiting the activity to evaluate the effect of the diaryl imidazole compound to treat Alzheimer's disease, and finds that the diaryl imidazole compound has good in vitro activity, and can be further developed as a precursor substance for performing the Alzheimer's disease resistant effect by inhibitingthe activity of cholinesterase. (The formula is shown in the description).
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Paragraph 0075;0078; 0079
(2019/02/21)
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- New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies
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Azole antifungals are potent inhibitors of fungal lanosterol 14α demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design, synthesis, and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125?μg/mL against Candida albicans. Additionally, some of our compounds, such as 19 (MIC: 0.25?μg/mL), were potent against resistant C.?glabrata, a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action, we performed computational analysis utilizing molecular docking and dynamics simulations on the C.?albicans and C.?glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19.
- Do?an, ?nci Selin,Sara?, Selma,Sari, Suat,Kart, Didem,E?siz G?khan, ?ebnem,Vural, ?mran,Dalkara, Sevim
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p. 124 - 138
(2017/03/02)
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- Discovery of in vitro antitubercular agents through in silico ligand-based approaches
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The development of new anti-tubercular agents represents a constant challenge mostly due to the insurgency of resistance to the currently available drugs. In this study, a set of 60 molecules were selected by screening the Asinex and the ZINC collections and an in house library by means of in silico ligand-based approaches. Biological assays in Mycobacterium tuberculosis H37Ra ATCC 25177 strain highlighted (±)-1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethyl-4-(3,4-dichlorophenyl)piperazine-1-carboxylate (5i) and 3-(4-chlorophenyl)-5-(2,4-dimethylpyrimidin-5-yl)-2-methylpyrazolo[1.5-a]pyrimidin-7(4H)-one (42) as the most potent compounds, having a Minimum Inhibitory Concentration (MIC) of 4 and 2 μg/4g/mL respectively. These molecules represent a good starting point for further optimization of effective anti-TB agents.
- De Vita, Daniela,Pandolfi, Fabiana,Cirilli, Roberto,Scipione, Luigi,Di Santo, Roberto,Friggeri, Laura,Mori, Mattia,Fiorucci, Diego,Maccari, Giorgio,Christopher, Robert Selwyne Arul,Zamperini, Claudio,Pau, Valentina,De Logu, Alessandro,Tortorella, Silvano,Botta, Maurizio
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p. 169 - 180
(2016/06/09)
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- Substituted imidazole-1-vinyl compound and use thereof
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The invention relates to a substituted imidazole-1-ethylene compound as well as a preparation and an application thereof. The substituted imidazole-1-ethylene compound is a compound shown as a formula I, or salts thereof formed with medicinal acids or bases. According to the antifungal activity test performed on eight clinical fungi by the compound provided in the invention, a good fungus killing effect is achieved. The compound can serve as a novel broad-spectrum antifungal activity compound and is developed into antifungal medicines, disinfectants or feed additives.
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Paragraph 0056; 0148-0151
(2016/10/27)
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- Structural basis for rational design of inhibitors targeting Trypanosoma cruzi Sterol 14α-demethylase: Two regions of the enzyme molecule potentiate its inhibition
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Chagas disease, which was once thought to be confined to endemic regions of Latin America, has now gone global, becoming a new worldwide challenge with no cure available. The disease is caused by the protozoan parasite Trypanosoma cruzi, which depends on the production of endogenous sterols, and therefore can be blocked by sterol 14α-demethylase (CYP51) inhibitors. Here we explore the spectral binding parameters, inhibitory effects on T. cruzi CYP51 activity, and antiparasitic potencies of a new set of β-phenyl imidazoles. Comparative structural characterization of the T. cruzi CYP51 complexes with the three most potent inhibitors reveals two opposite binding modes of the compounds ((R)-6, EC50 = 1.2 nM, vs (S)-2/(S)-3, EC50 = 1.0/5.5 nM) and suggests the entrance into the CYP51 substrate access channel and the heme propionate-supporting ceiling of the binding cavity as two distinct areas of the protein that enhance molecular recognition and therefore could be used for the development of more effective antiparasitic drugs.
- Friggeri, Laura,Hargrove, Tatiana Y.,Rachakonda, Girish,Williams, Amanda D.,Wawrzak, Zdzislaw,Di Santo, Roberto,De Vita, Daniela,Waterman, Michael R.,Tortorella, Silvano,Villalta, Fernando,Lepesheva, Galina I.
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p. 6704 - 6717
(2014/09/29)
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- Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors
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Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of immune responses and therefore an important therapeutic target for the treatment of diseases that involve pathological immune escape, such as cancer. Here, we describe a robust and sensitive high-throughput screen (HTS) for IDO1 inhibitors using the Prestwick Chemical Library of 1200 FDA-approved drugs and the Maybridge HitFinder Collection of 14,000 small molecules. Of the 60 hits selected for follow-up studies, 14 displayed IC50 values below 20 μM under the secondary assay conditions, and 4 showed an activity in cellular tests. In view of the high attrition rate we used both experimental and computational techniques to identify and to characterize compounds inhibiting IDO1 through unspecific inhibition mechanisms such as chemical reactivity, redox cycling, or aggregation. One specific IDO1 inhibitor scaffold, the imidazole antifungal agents, was chosen for rational structure-based lead optimization, which led to more soluble and smaller compounds with micromolar activity.
- R?hrig, Ute F.,Majjigapu, Somi Reddy,Chambon, Marc,Bron, Sylvian,Pilotte, Luc,Colau, Didier,Van Den Eynde, Beno?t J.,Turcatti, Gerardo,Vogel, Pierre,Zoete, Vincent,Michielin, Olivier
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p. 284 - 301
(2014/08/05)
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- Synthesis and biological evaluation of novel azole derivatives as selective potent inhibitors of brassinosteroid biosynthesis
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Brassinosteroids (BRs) are phytohormones that control several important agronomic traits, such as flowering, plant architecture, seed yield, and stress tolerance. To manipulate the BR levels in plant tissues using specific inhibitors of BR biosynthesis, a series of novel azole derivatives were synthesized and their inhibitory activity on BR biosynthesis was investigated. Structure-activity relationship studies revealed that 2RS, 4RS-1-[4-(2- allyloxyphenoxymethyl)-2-(4-chlorophenyl)-[1,3]dioxolan-2-ylmethyl]-1H-[1,2,4] triazole (G2) is a highly selective inhibitor of BR biosynthesis, with an IC50 value of approximately 46 ± 2 nM, which is the most potent BR biosynthesis inhibitor observed to date. Use of gibberellin (GA) biosynthesis mutants and BR signaling mutants to analyze the mechanism of action of this synthetic series indicated that the primary site of action is BR biosynthesis. Experiments feeding BR biosynthesis intermediates to chemically treated Arabidopsis seedlings suggested that the target sites of this synthetic series are CYP90s, which are responsible for the C-22 and/or C-23 hydroxylation of campesterol.
- Yamada, Kazuhiro,Yajima, Osamu,Yoshizawa, Yuko,Oh, Keimei
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p. 2451 - 2461
(2013/06/27)
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- Imidazole incorporated semicarbazone derivatives as a new class of anticonvulsants: Design, synthesis and in-vivo screening
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A series of novel imidazole incorporated semicarbazones was synthesized using an appropriate synthetic route and characterized by spectral analysis (IR, 1H NMR, 13C NMR and Mass). The anticonvulsant activity of the synthesized compounds was determined using doses of 30, 100, and 300 mg kg-1 against maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ) induced seizure and minimal neurotoxicity test. Six compounds exhibited protection in both models and 2-(1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethylidene)-N-p- tolylsemicarbazone emerged as the most active compound of the series without any neurotoxicity and significant CNS depressant effect. Liver enzyme estimations (SGOT, SGPT, Alkaline phosphatase) of the compound also showed no significant change in the enzymes levels. Moreover, it caused 80% elevation of γ-amino butyric acid (GABA) levels in the whole mice brain, thus indicating that it could be a promising candidate in designing of a potent anticonvulsant drug.
- Amir, Mohammad,Ali, Israr,Hassan, Mohd. Zaheen
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p. 571 - 580
(2013/07/28)
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- Synthesis and antifungal activity of a new series of 2-(1H-imidazol-1-yl)- 1-phenylethanol derivatives
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A new series of aromatic ester and carbamate derivatives of 2-(1H-imidazol-1-yl)-1-phenylethanol were synthesized and evaluated for their antifungal activity towards Candida albicans and non-albicans Candida species strains. The aromatic biphenyl ester derivatives 6a-c were more active than the reference compound fluconazole. 6c possesses a MIC mean values of 1.7 ± 1.4 μg mL-1 vs C. albicans and 1.9 ± 2.0 μg mL -1 vs non-albicans Candida species strains. The racemic mixtures of 6a, b were purified to afford the pure enantiomers. The (-) isomers were up to 500 times more active than (+) isomers. (-)-6a and (-)-6b were thirty and ninety times more active than fluconazole towards C. krusei strain respectively. The racemates of 6a-c showed low cytotoxicity against human monocytic cell line (U937) with 6a demonstrating a CC50 greater than 128 μg mL -1.
- De Vita, Daniela,Scipione, Luigi,Tortorella, Silvano,Mellini, Paolo,Di Rienzo, Barbara,Simonetti, Giovanna,D'Auria, Felicia Diodata,Panella, Simona,Cirilli, Roberto,Di Santo, Roberto,Palamara, Anna Teresa
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body text
p. 334 - 342
(2012/04/10)
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- Anti-Plasmodium activity of imidazolium and triazolium salts
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We have previously reported that tetrazolium salts were both potent and specific inhibitors of Plasmodium replication, and that they appear to interact with a parasite component that is both essential and conserved. The use of tetrazolium salts in vivo is limited by the potential reduction of the tetrazolium ring to form an inactive, neutral acyclic formazan. To address this issue imidazolium and triazolium salts were synthesized and evaluated as Plasmodium inhibitors. Many of the imidazolium and triazolium salts were highly potent with active concentrations in the nanomolar range in Plasmodium falciparum cultures, and specific to Plasmodium with highly favorable therapeutic ratios. The results corroborate our hypothesis that an electron-deficient core is required so that the compound may thereby interact with a negatively charged moiety on the parasite merozoite; the side groups in the compound then form favorable interactions with adjacent parasite components and thereby determine both the potency and selectivity of the compound.
- Vlahakis, Jason Z.,Lazar, Carmen,Crandall, Ian E.,Szarek, Walter A.
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experimental part
p. 6184 - 6196
(2010/09/14)
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- Heme oxygenase inhibition by 1-Aryl-2-(1H-imidazol-1-yl/1H-1,2,4-triazol-1- yl)ethanones and their derivatives
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Previous studies by our research group have been concerned with the design of selective inhibitors of heme oxygenases (HO-1 and HO-2). The majority of these were based on a four-carbon linkage of an azole, usually an imidazole, and an aromatic moiety. In the present study, we designed and synthesized a series of inhibition candidates containing a shorter linkage between these groups, specifically, a series of 1-aryl-2-(1H-imidazol-1-yl/1H-1,2,4-triazol-1-yl) ethanones and their derivatives. As regards HO-1 inhibition, the aromatic moieties yielding best results were found to be halogen-substituted residues such as 3-bromophenyl, 4-bromophenyl, and 3,4-dichlorophenyl, or hydrocarbon residues such as 2-naphthyl, 4-biphenyl, 4-benzylphenyl, and 4-(2-phenethyl)phenyl. Among the imidazole-ketones, five (36-39, and 44) were found to be very potent (IC5050 in favor of HO-1. In the case of the azole-dioxolanes, two of them (80 and 85), each possessing a 2-naphthyl moiety, were found to be particularly potent and selective HO-1 inhibitors. Three non-carbonyl analogues (87, 89, and 91) of 1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanone were found to be good inhibitors of HO-1. For the first time in our studies, two azole-based inhibitors (37 and 39) were found to exhibit a modest selectivity index in favor of HO-2. The present study has revealed additional candidates based on inhibition of heme oxygenases for potentially useful pharmacological and therapeutic applications.
- Roman, Gheorghe,Vlahakis, Jason Z.,Vukomanovic, Dragic,Nakatsu, Kanji,Szarek, Walter A.
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experimental part
p. 1541 - 1555
(2011/11/29)
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- 2-Aryl-3-(1H-azol-1-yl)-1H-indole derivatives: A new class of antimycobacterial compounds - Conventional heating in comparison with MW-assisted synthesis
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2-Aryl-3-(1H-imidazol-1-yl and 1H-1,2,4-triazol-1-yl)-1H-indole derivatives were synthesized and tested for their in-vitro antifungal and antimycobacterial activities. These indole derivatives were devoid of antifungal activity against the tested strains of Candida spp. Yet, they exhibited an interesting antitubercular activity against Mycobacterium tuberculosis reference strain H37Rv.
- Zampieri, Daniele,Mamolo, Maria Grazia,Laurini, Erik,Scialino, Giuditta,Banfi, Elena,Vio, Luciano
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scheme or table
p. 716 - 722
(2010/07/04)
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- Antifungal and antimycobacterial activity of 1-(3,5-diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives
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1-(3,5-Diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives were synthesized and tested for their in vitro antifungal and antimycobacterial activities. These imidazole derivatives showed an excellent antifungal activity against a clinical strain of Candida albicans and an interesting antitubercular activity againstMycobacterium tuberculosis H37Rv reference strain.
- Zampieri, Daniele,Mamolo, Maria Grazia,Laurini, Erik,Scialino, Giuditta,Banfi, Elena,Vio, Luciano
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p. 4516 - 4522
(2008/09/21)
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- A new series of miconazole analogs: Synthesis and in vitro antifungal and antimycobacterial activities
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The synthesis and antimicrobial activity of new miconazole analogs are reported. All compounds showed good antimycobacterial activity; some of them were also active against some strains of Candida albicans and Candida sp.. Of the synthesized compounds, two showed good activity both against some strains of Mycobacterium and some strains of Candida. Structure-activity relationships are discussed.
- Fioravanti, Rossella,Biava, Mariangela,Porretta, Giulio Cesare,Lampis, Giorgio,Deidda, Delia,Pompei, Raffaello
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p. 162 - 175
(2007/10/03)
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- Synthesis and antifungal activity of novel (1-aryl-2-heterocyclyl)ethylideneaminooxymethyl-substituted dioxolanes
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A novel series of (1-aryl-2-heterocyclyl)ethylideneaminooxymethyl-substituted dioxolanes IIIa-n were synthesized by condensation of substituted 1,3-dioxolan-4-ylmethyl p-toluenesulfonates 4 with 1-(hydroxyimino)-1-aryl-2-heterocyclylethanes 5.Compounds IIIa-n were found to have effective in vitro antifungal activity when evaluated against the pathogenic fungi Candida albicans, Aspergillus flavus and Fusarium solani with MIC (minimum inhibitory concentration values of 10 μg*ml-1 for IIIa-l and 5 μg*ml-1 for IIIm,n. antifungal activity / 1,3-dioxolane / ethylideneaminooxy / imidazole / 1,2,4-triazole
- Baji, H.,Flammang, M.,Kimny, T.,Gasquez, F.,Compagnon, P. L.,Delcourt, A.
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p. 617 - 626
(2007/10/02)
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- Research on antibacterial and antifungal agents. X. Synthesis and antimicrobial activities of 1-phenyl-2-(1H-azol-1-yl) ethane derivatives. Anticonvulsant activity of 1-(4-methylphenyl)-2-(1H-imidazol-1-yl) ethanol.
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The synthesis and antimicrobial activity of new phenylazolylethane derivatives are reported.Antimicrobial data in comparison with those obtained with miconazole, fluconazole, enilconazole, imazalil sulfate, pipemidic acid and minocycline showed that tested compounds generally possessed poor or weak activity.Toxicity and anticonvulsant activity of 1-(4-methylphenyl)-2-(1H-imidazol-1-yl)ethanol and structural likeness to Denzimol were also tested.The obtained results showed interesting anticonvulsant activity but only on the supraspinal region. azoles / antifungal / anticonvulsant agent
- Porretta, G. C.,Fioravanti, R.,Biava, M.,Cirilli, R.,Simonetti, N.,et al.
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p. 749 - 760
(2007/10/02)
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- Synthesis and 13C NMR Spectra of cis- and trans-methyl>>-1,3-dioxolane-4-methanols
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Syntheses and 13C nmr spectra of a number of cis and trans 2-(haloaryl)-2--4-(hydroxymethyl)-1,3-dioxolanes are described.The haloaryl groups are 2,4-dichloro, 2,4-difluoro-, 4-chloro- and 4-bromophenyl.In these series, some of the cis compounds become available through crystalline bromo benzoates 5.Separations of some trans isomers are achieved through fractional crystallizations of imidazolyl benzoate nitrates 6.Stereochemical assignments are based primarily on one major 13C chemical shift difference, namely that of C-4 of the 1,3-dioxolane ring, the chemical shift of the trans isomers being 1.0-2.5 ppm downfield from that of the cis isomers.
- Chapman, David R.,Bauer, Ludwig
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p. 2053 - 2061
(2007/10/02)
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- Substituted 3,5-diphenyl-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidines
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Substituted 3,5-diphenyl-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidines in which hydrogens of their phenyl rings may be replaced by halogen, lower alkoxy or lower alkyl groups are useful as antifungal agents.
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- Process for the stereospecific preparation of imidazolyl oximes
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1-Aryl-2-(1H-imidazol-1-yl)-ethanone oxime ethers are known to exist as a mixture of isomers corresponding to the formulae: STR1 To prepare such an isomer in a stereospecifically pure form, the pure stereoisomer of the corresponding ethanone oxime is first converted into an alkali salt in a polar solvent, such as acetone or dimethylformamide, using an alkali in an amount somewhat less than the equimolar amount with respect to the said ethanone oxime, and is then converted to the desired ether by reacting it at a temperature not higher than 40° C. with a halogen compound capable of forming the desired ether. Isolation of the ether product is obtained as the free base or by precipitating it as an acid addition salt upon addition of a suitable organic or mineral acid, preferably nitric acid. A stereospecific ethanone oxime in either its trans- or cis-isomer form corresponding to the formula: STR2 can be stereospecifically synthesized from the corresponding 2-halogen ethanone having the formula A--CO--CH2 --Hal (IV) which, in making the cis oxime (IIc), is first converted with imidazole or a suitably substituted derivative thereof and subsequently oximated by reaction with hydroxylamine in the presence of a molar excess of an alkali at an elevated temperature; or which, in preparing the trans oxime (IIt), is first oximated by reaction with hydroxyl-amine under mild conditions and subsequently converted in the cold with imidazole or a suitably substituted derivative thereof. The products are effective fungicides or bactericides and consequently useful as thermotherapeutic agents in combatting undesirable lower plant organisms in the fields of human as well as veterinary medicine and also as fungicides in agriculture and horticulture.
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