- Discovery of a new potent inhibitor of mushroom tyrosinase (Agaricus bisporus) containing 4-(4-hydroxyphenyl)piperazin-1-yl moiety
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Tyrosinase (TYR, EC 1.14.18.1) plays a pivotal role in mammalian melanogenesis and enzymatic browning of plant-derived food. Therefore, tyrosinase inhibitors (TYRIs) can be of interest in cosmetics and pharmaceutical industries as depigmentation compounds
- Buemi, Maria Rosa,De Luca, Laura,Fais, Antonella,Gitto, Rosaria,Mirabile, Salvatore,Pintus, Francesca,Rapisarda, Antonio,Vittorio, Serena,Germanò, Maria Paola
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- Indoles and 1-(3-(benzyloxy)benzyl)piperazines: Reversible and selective monoamine oxidase B inhibitors identified by screening an in-house compound library
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The therapeutic indications for monoamine oxidases A and B (MAO-A and MAO-B) inhibitors that have emerged from biological studies on animal and cellular models of neurological and oncological diseases have focused drug discovery projects upon identifying
- ?akelj, Simon,Frlan, Rok,Gobec, Stanislav,Hrast, Martina,Knez, Damijan,Kos, Janko,Pi?lar, Anja
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- A new n-substituted 1h-isoindole-1,3(2h)-dione derivative— synthesis, structure and affinity for cyclooxygenase based on in vitro studies and molecular docking
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Isoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1H-isoindole-1,3(2H)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new
- Szkatu?a, Dominika,Krzy?ak, Edward,Stanowska, Paulina,Duda, Magdalena,Wiatrak, Benita
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- Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents
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(+)-Usnic acid, a product of secondary metabolism in lichens, has displayed a broad range of biological properties such as antitumor, antimicrobial, antiviral, anti-inflammatory, and insecticidal activities. Interested by these pharmacological activities and to tap into its potential, we herein present the synthesis and biological evaluation of new usnic acid enaminone-conjugated 1,2,3-triazoles 10-44 as antimycobacterial agents. (+)-Usnic acid was condensed with propargyl amine to give usnic acid enaminone 8 with a terminal ethynyl moiety. It was further reacted with various azides A1-A35 under copper catalysis to give triazoles 10-44 in good yields. Among the synthesized compounds, saccharin derivative 36 proved to be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 μM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 μM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl] and 29 (N-acylmorpholinyl) showing inhibitory concentrations of 41 and 90.7 μM, respectively, while they were inactive on the other tested bacterial strains. Overall, the study presented here is useful for converting natural (+)-usnic acid into antitubercular and antibacterial agents via incorporation of enaminone and 1,2,3-triazole functionalities.
- Bangalore, Pavan K.,Vagolu, Siva K.,Bollikanda, Rakesh K.,Veeragoni, Dileep K.,Choudante, Pallavi C.,Misra, Sunil,Sriram, Dharmarajan,Sridhar, Balasubramanian,Kantevari, Srinivas
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supporting information
p. 26 - 35
(2020/01/03)
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- Synthesis, anticancer evaluation and molecular docking studies of new benzimidazole- 1,3,4-oxadiazole derivatives as human topoisomerase types I poison
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In this study, some benzimidazole-oxadiazole derivatives were synthesised and tested for their in vitro anticancer activities on five cancer cell lines, including HeLa, MCF7, A549, HepG2 and C6. Their structures were elucidated by IR, 1H-NMR,
- Acar ?evik, Ulviye,Atl? Eklio?lu, ?zlem,Atl?d, ?zlem,Kaplanc?kl?, Zafer As?m,Karaduman, Abdullah Burak,Kaya ?avu?o?lu, Betül,Levent, Serkan,Osmaniye, Derya,Sa?l?k, Begüm Nurpelin
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p. 1657 - 1673
(2020/08/21)
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- Design and synthesis of C-19 isosteviol derivatives as potent and highly selective antiproliferative agents
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Six series of novel isosteviol derivatives; modified in the C-19 position; were synthesized; and their antiproliferative activity was evaluated against three human cancer cell lines (HCT-116; BEL-7402; HepG2) and the human L02 normal cell line in vitro. M
- Luan, Tian,Cao, Li-Hua,Deng, Hao,Shen, Qing-Kun,Tian, Yu-Shun,Quan, Zhe-Shan
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- Betulinic acid derivatives: a new class of α-glucosidase inhibitors and LPS-stimulated nitric oxide production inhibition on mouse macrophage RAW 264.7 cells
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Chemical manipulation studies were conducted on betulinic acid (1), twenty-one new rationally designed analogues of 1 with modifications at C-28 were synthesized for their evaluation of inhibitory effects on α-glucosidase and LPS-stimulated nitric oxide production in mouse macrophage RAW 264.7 cells. Compound 2 (IC50 = 5.4 μM) exhibited an almost 1.4-fold increase in α-glucosidase inhibitory activity on yeast α-glucosidase while analogues 5 (IC50 16.4 μM) and 11 (IC50 16.6 μM) exhibited a 2-fold enhanced inhibitory activity on NO-production than betulinic acid.
- Gundoju, Narayanarao,Bokam, Ramesh,Yalavarthi, Nageswara Rao,Azad, Rajaram,Ponnapalli, Mangala Gowri
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p. 2618 - 2622
(2018/04/30)
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- Design, synthesis, in vitro and in vivo evaluation of novel pyrrolizine-based compounds with potential activity as cholinesterase inhibitors and anti-Alzheimer's agents
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Novel series of pyrrolizine based compounds (4–6 and 9–11) were designed, synthesized and evaluated as potential anti-Alzheimer agents. Most of the tested compounds showed selectivity to hAChE over hBChE and effectively inhibited self–induced amyloid beta
- El-Sayed, Nehad Abou-Elmagd,Farag, Awatef El-Said,Ezzat, Manal Abdel Fattah,Akincioglu, Hulya,Gül?in, ?lhami,Abou-Seri, Sahar Mahmoud
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- New thiazolidine-2,4-dione derivatives combined with organometallic ferrocene: Synthesis, structure and antiparasitic activity
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Favourable physicochemical properties of an organometallic ferrocene and antiplasmodial potency of compounds containing the thiazolidine-2,4-dione framework (TZD-4) prompted us to explore compounds containing both the thiazolidine-2,4-dione core and the ferrocenyl unit with the primary aim of identifying compounds with promising antiprotozoal activities. Thus, a new series of rationally designed ferrocene-based thiazolidine-2,4-dione derivatives, containing a selection of secondary cyclic amines, was synthesised and fully characterised using standard spectroscopic techniques. The resulting compounds were screened for their antiplasmodial and antitrypanosomal activities against both the chloroquine-resistant (Dd2) strain of Plasmodium falciparum and the Nagana Trypanosoma brucei brucei 427. The general trend that emerged indicated that the target compounds were more selective towards T. b. brucei compared to the P. falciparum parasite. Moreover, the analogues bearing methylpiperazine (8a) and piperidine (8b) rings were more active against T. b. brucei compared to hit compound TZD-4. Except compound 8b, which appeared promising, none of the synthesised compounds showed better activity than TZD-4 against the P. falciparum parasite. All the synthesised compounds were non-toxic and often showed >90% viability of the HeLa cell line screened.
- Oderinlo, Ogunyemi O.,Tukulula, Matshawandile,Isaacs, Michelle,Hoppe, Heinrich C.,Taylor, Dale,Smith, Vincent J.,Khanye, Setshaba D.
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- Containing substituted piperazinyl such Thienopyridine tenuifoliae derivatives and process for their preparation and use
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The invention belongs to the technical field of anti-platelet aggregation drugs and provides substituent piperazinyl-containing thienopyridine ester derivatives. The molecular formula of the derivatives are as shown in the specification, wherein n1 can be
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Paragraph 0041-0044
(2017/02/24)
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- Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2
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Following a structure-based virtual screening, a series of 2,4 thiazolidinediones was synthesized in order to explore structure activity relationships for inhibition of the Plasmodium falciparum cysteine protease falcipain-2 (FP-2) and of whole cell antiparasitic activity. Most compounds exhibited low micromolar antiplasmodial activities against the P. falciparum drug resistant W2 strain. The most active compounds of the series were tested for in vitro microsomal metabolic stability and found to be susceptible to hepatic metabolism. Subsequent metabolite identification studies highlighted the metabolic hot spots. Molecular docking studies of a frontrunner inhibitor were carried out to determine the probable binding mode of this class of inhibitors in the active site of FP-2.
- Sharma, Rajni Kant,Younis, Yassir,Mugumbate, Grace,Njoroge, Mathew,Gut, Jiri,Rosenthal, Philip J.,Chibale, Kelly
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p. 507 - 518
(2015/02/19)
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- Chloroquinoline-acetamide hybrids: A promising series of potential antiprotozoal agents
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In an endeavour to develop efficacious antiprotozoal agents 2-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]acetamide derivatives were synthesized and screened in vitro against the HM1:IMSS strain of E. histolytica and 3D7 strain of P. falciparum. Among the twenty-seven synthesized compounds, eleven evinced propitious anti-amoebic activity with IC50 values ranging from 0.41 to 1.80 μM) lower than the standard drug metronidazole (IC50 1.80 μM). All the compounds inhibited the in vitro growth of P. falciparum (IC50 range: 0.30-33.52 μM). Compounds A22 and A25 were found to be the most active antimalarial derivatives, and compound A16 the most active in inhibiting β-haematin formation; however compound A25 displayed the more favourable safety profile. The crystal structure for the compounds A7, A8, A12 and A21 was also determined. The molecular docking of crystal resolved inhibitors with PfDHFR allowed identification of stabilizing interactions within enzyme active sites. These compounds affirm the potential for further derivatives to enhance antiprotozoal activity whilst retaining their safety profile.
- Inam, Afreen,Van Zyl, Robyn L.,Van Vuuren, Natasha J.,Chen, Chien-Teng,Avecilla, Fernando,Agarwal, Subhash M.,Azam, Amir
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p. 48368 - 48381
(2015/06/16)
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- Molecular design and synthesis of 1,4-disubstituted piperazines as α1-adrenergic receptor blockers
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A new series of 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide and 3,5,6,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin- 4-one derivatives were designed, synthesized, their binding and functional properties as α1-adrenorec
- Abou El-Ella, Dalal A.,Hussein, Mohammed M.,Serya, Rabah A.T.,Abdel Naby, Rana M.,Al-Abd, Ahmed M.,Saleh, Dalia O.,El-Eraky, Wafaa I.,Abouzid, Khaled A.M.
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- Bioconjugatable azo-based dark-quencher dyes: Synthesis and application to protease-activatable far-red fluorescent probes
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We describe the efficient synthesis and one-step derivatization of novel, nonfluorescent azo dyes based on the Black Hole Quencher-3 (BHQ-3) scaffold. These dyes were equipped with various reactive and/or bioconjugatable groups (azido, α-iodoacetyl, keton
- Chevalier, Arnaud,Massif, Cédrik,Renard, Pierre-Yves,Romieu, Anthony
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p. 1686 - 1699
(2013/04/10)
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- NOVEL PYRAZOLYLMETHYLAMINE COMPOUNDS AS CALCIUM CHANNEL MODULATORS AND PREPARATION METHOD THEREOF
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The present invention relates to pyrazolylmethylamine-piperazine derivatives and their pharmaceutically acceptable salts effective as calcium channel modulators and a method of manufacturing the same. The present invention also relates to the medicinal us
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Page/Page column 10
(2010/04/30)
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- Synthesis of triazole-linked glycoconjugates by copper(I)-catalyzed regiospecific cycloaddition of alkynes and azides
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Several 1,2,3-triazole-linked glycoconjugates were efficiently synthesized via a Cu(I)-mediated 1,3-dipolar cycloaddition with high regiospecificity and yield (≥85%), providing a simple and efficient route to synthesize protected and unprotected neoglycoconjugates. Introduction of a spacer between glycosyl moieties and other compounds reduces steric hindrance, promotes yield, and expands the varieties of glycoconjugates to satisfy various needs of biological events. The structures of all the synthesized glycoconjugates were clearly confirmed by infrared(IR), 1H NMR, 13C NMR, elemental analysis (EA), or MS. Copyright Taylor & Francis Group, LLC.
- Zhang, Xiaoru,Yang, Xiaohui,Zhang, Shusheng
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experimental part
p. 830 - 844
(2009/08/08)
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- Structurally constrained hybrid derivatives containing octahydrobenzo[g or f]quinoline moieties for dopamine D2 and D3 receptors: Binding characterization at D2/D3 receptors and elucidation of a pharmacophore model
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A series of structurally constrained analogues based on hybrid compounds containing octahydrobenzo[g or f]quinoline moieties were designed, synthesized, and characterized for their binding to dopamine D2 and D3 receptors expressed in HEK-293 cells. Among the newly developed constrained molecules, trans-octahydrobenzo[f]quinolin-7-ol (8) exhibited the highest affinity for D2 and D3 receptors, the (-)-isomer being the eutomer. Interestingly, this hybrid constrained version 8 showed significant affinity over the corresponding nonhybrid version 1 (representing a constrained version of the aminotetralin structure only) when assayed under same conditions (Ki of 49.1 and 14.9 nM for 8 vs 380 and 96.0 nM for 1 at D2 and D3, respectively). Similar results were found with other lead hybrid compounds, indicating a contribution of the piperazine moiety in the observed enhanced affinity. On the basis of the data of new lead constrained derivatives and other lead hybrid derivatives developed by us, a unique pharmacophore model was proposed consisting of three pharmacophoric centers, two with aromatic/hydrophobic and one with cationic features.
- Brown, Dennis A.,Kharkar, Prashant S.,Parrington, Ingrid,Reith, Maarten E. A.,Dutta, Aloke K.
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experimental part
p. 7806 - 7819
(2009/12/07)
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- Bioisosteric heterocyclic versions of 7-{[2-(4-phenyl-piperazin-1-yl)ethyl] propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol: Identification of highly potent and selective agonists for dopamine D3 receptor with potent in vivo activity
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In the current report, we extend the SAR study on our hybrid structure 7-{[2-(4-phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen- 2-ol further to include heterocyclic bioisosteric analogues. Binding assays were carried out with HEK-29
- Biswas, Swati,Hazeldine, Stuart,Ghosh, Balaram,Parrington, Ingrid,Kuzhikandathil, Eldo,Reith, Maarten E. A.,Dutta, Aloke K.
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experimental part
p. 3005 - 3019
(2009/04/06)
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- NO-donors. Part 171: Synthesis and antimicrobial activity of novel ketoconazole-NO-donor hybrid compounds
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Novel hybrid compounds combining the antifungal drug ketoconazole with a diazen-1-ium-1,2-diolate or an organic nitrate moiety and the corresponding NO-donors without ketoconazole were synthesized and their activities against a broad variety of fungal strains were tested. Hybridization modifies the spectrum of antimicrobial activities and generally, the ketoconazole-NO-donor hybrids are more potent than ketoconazole. The NO-donors alone show insufficient effectiveness.
- Konter, Joerg,Moellmann, Ute,Lehmann, Jochen
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p. 8294 - 8300
(2008/12/23)
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- Substituted uracil derivatives as potent inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)
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A new class of PARP-1 inhibitors, namely substituted fused uracil derivatives were synthesised. Starting from a derivative with an IC50=2 μM the chemical optimisation program led to compounds with more than a 100-fold increase in potency (ICsu
- Steinhagen, Henning,Gerisch, Michael,Mittendorf, Joachim,Schlemmer, Karl-Heinz,Albrecht, Barbara
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p. 3187 - 3190
(2007/10/03)
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- Synthesis of new 5-substituted 1,2,4-triazole-3-thione derivatives
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In the present paper we describe the preparation of series of new derivatives of 1,2,4-triazole-3-thiol. As starting materials methyl 3-acyldithiocarbazates were used, which on reaction with amines gave the corresponding 4,5-disubstituted 1,2,4-triazole-3-thiol derivatives (3). Into the 4-position of the 1,2,4-triazole-3-thiol system a β-hydroxyetlhyl substituent was introduced (compounds 4). These compounds were alkylated with methyl iodide to from 6, with N-substituted amides of chloroacetic acid (products 7 and 8), and aminomethylated with formation of Mannich bases (10). Some of the thiols 4 were desulfurized to 9. The new compounds were tested for their circulatory activity, but found not pharmacologically active.
- Foks, Henryk,Czarnocka-Janowicz, Anna,Rudnicka, Waleria,Trzeciak, Henryk
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- Synthesis and serotonergic activity of arylpiperazide derivatives of serotonin: Potent agonists for 5-HT(1D) receptors
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A series of new arylpiperazide derivatives of serotonin has been prepared and evaluated as 5-HT(1D) receptor agonists. Binding experiments at cloned human 5-HT(1Dα), 5-HT(1Dβ), and 5-HT(1A) receptors show that all the compounds are very potent and selecti
- Perez,Fourrier,Sigogneau,Pauwels,Palmier,John,Valentin,Halazy
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p. 3602 - 3607
(2007/10/03)
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