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4-Aminoquinoline Compound

Luciana Maria Ribeiro Antinarelli, Isabela de Oliveira Souza, Nicolas Glanzmann, Ayla das Chagas Almeida, Gabriane Nascimento Porcino, Eveline Gomes Vasconcelos, Adilson David da Silva, Elaine Soares Coimbra
In this study, we have investigated the antileishmanial activity of ten 7-chloro-4-quinolinylhydrazone derivatives. Among the compounds tested, compounds 2a and 2j presented activity against promastigotes (IC50 values of 52.5 and 21.1 μM, respectively) and compounds 2a and 2c were active against intracellular amastigotes (IC50 of 8.1 and 15.6 μM, respectively) of Leishmania amazonensis. The majority of compounds did not show toxicity against murine macrophages. Compound 2a exhibited low cytotoxicity to human erythrocytes and induced an oxidative imbalance in promastigote forms, reflected by an increase in the formation of reactive oxygen species (ROS) and a reduction of mitochondrial membrane potential...
October 12, 2016: Experimental Parasitology
Runzhe Song, Zhaomeng Han, Qiuqin He, Renhua Fan
Dearomatization provides numerous possibilities for the development of new transformative modes of aromatic compounds. A conceptually novel metal-free multicomponent domino reaction of the dearomatized products of 2-alkynylanilines is developed. The reaction involves the secondary amine-mediated transimination with α-amino nitriles and subsequent aromatization-triggered cascade rearrangement, nucleophilic cyclization, and retro-Strecker reaction. This process provided a new practical method for the rapid synthesis of polyfunctionalized 4-aminoquinolines from readily available starting materials...
October 5, 2016: Organic Letters
Nicolas Chopin, Shinya Iikawa, Julien Bosson, Adeline Lavoignat, Guillaume Bonnot, Anne-Lise Bienvenu, Stéphane Picot, Jean-Philippe Bouillon, Maurice Médebielle
In this Letter we report on an efficient and short 2-3 steps synthesis of γ-hydroxy-γ-lactam derived-tetramates bearing a 7-chloro-4-aminoquinoline skeleton and their evaluation as potent antimalarials. These molecules were obtained through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of 7-chloro-4-aminoquinoline-derived amines. In vitro antimalarial activity of these new γ-lactams was evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and they were found to be active in the range of 14-827nM with generally good resistance index...
September 15, 2016: Bioorganic & Medicinal Chemistry Letters
Irene Sola, Albert Artigas, Martin C Taylor, F Javier Pérez-Areales, Elisabet Viayna, M Victòria Clos, Belén Pérez, Colin W Wright, John M Kelly, Diego Muñoz-Torrero
Current drugs against human African trypanosomiasis (HAT) suffer from several serious drawbacks. The search for novel, effective, brain permeable, safe, and inexpensive antitrypanosomal compounds is therefore an urgent need. We have recently reported that the 4-aminoquinoline derivative huprine Y, developed in our group as an anticholinesterasic agent, exhibits a submicromolar potency against Trypanosoma brucei and that its homo- and hetero-dimerization can result in to up to three-fold increased potency and selectivity...
November 1, 2016: Bioorganic & Medicinal Chemistry
Anatolii R Syniugin, Olga V Ostrynska, Maksym O Chekanov, Galyna P Volynets, Sergiy A Starosyla, Volodymyr G Bdzhola, Sergiy M Yarmoluk
In this article, the derivatives of 3-quinoline carboxylic acid were studied as inhibitors of protein kinase CK2. Forty-three new compounds were synthesized. Among them 22 compounds inhibiting CK2 with IC50 in the range from 0.65 to 18.2 μM were identified. The most active inhibitors were found among tetrazolo-quinoline-4-carboxylic acid and 2-aminoquinoline-3-carboxylic acid derivatives.
September 2, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
Darren J Creek, Hwa H Chua, Simon A Cobbold, Brunda Nijagal, James I Macrae, Benjamin K Dickerman, Paul R Gilson, Stuart A Ralph, Malcolm J McConville
High-throughput phenotypic screening of chemical libraries has resulted in the identification of thousands of compounds with potent antimalarial activity, although in most cases, the mechanism(s) of action of these compounds remain unknown. Here we have investigated the mode of action of 90 antimalarial compounds derived from the Malaria Box collection using high-coverage, untargeted metabolomics analysis. Approximately half of the tested compounds induced significant metabolic perturbations in in vitro cultures of P...
August 29, 2016: Antimicrobial Agents and Chemotherapy
Madhulata Kumari, Subhash Chandra, Neeraj Tiwari, Naidu Subbarao
BACKGROUND: The Plasmodium falciparum M18 Aspartyl Aminopeptidase (PfM18AAP) is only aspartyl aminopeptidase which is found in the genome of P. falciparum and is essential for its survival. The PfM18AAP enzyme performs various functions in the parasite and the erythrocytic host such as hemoglobin digestion, erythrocyte invasion, parasite growth and parasite escape from the host cell. It is a valid target to develop antimalarial drugs. In the present work, we employed 3D QSAR modeling, pharmacophore modeling, and molecular docking to identify novel potent inhibitors that bind with M18AAP of P...
2016: BMC Structural Biology
Guilherme Curty Lechuga, Júlio Cesar Borges, Claudia Magalhães Calvet, Humberto Pinheiro de Araújo, Aline Araujo Zuma, Samara Braga do Nascimento, Maria Cristina Machado Motta, Alice Maria Rolim Bernardino, Mirian Claudia de Souza Pereira, Saulo Cabral Bourguignon
Chagas disease is a neglected tropical disease caused by the flagellated protozoan Trypanosoma cruzi. The current drugs used to treat this disease have limited efficacy and produce severe side effects. Quinolines, nitrogen heterocycle compounds that form complexes with heme, have a broad spectrum of antiprotozoal activity and are a promising class of new compounds for Chagas disease chemotherapy. In this study, we evaluated the activity of a series of 4-arylaminoquinoline-3-carbonitrile derivatives against all forms of Trypanosoma cruzi in vitro...
July 14, 2016: International Journal for Parasitology, Drugs and Drug Resistance
Alba Montoya, Jairo Quiroga, Rodrigo Abonia, Marcos Derita, Maximiliano Sortino, Alfredo Ornelas, Susana Zacchino, Braulio Insuasty
Twenty-four new hybrid analogues (15-38) containing 7-chloro-4-aminoquinoline and 2-pyrazoline N-heterocyclic fragments were synthesized. Twelve of the new compounds were evaluated against 58 human cancer cell lines by the U.S. National Cancer Institute (NCI). Compounds 25, 30, 31, 36, and 37 showed significant cytostatic activity, with the most outstanding GI50 values ranging from 0.05 to 0.95 µM. The hybrid compounds (15-38) were also evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yao Chen, Yaoyao Bian, Yuan Sun, Chen Kang, Sheng Yu, Tingming Fu, Wei Li, Yuqiong Pei, Haopeng Sun
Inhibition of acetylcholinesterase (AChE) using small molecules is still one of the most successful therapeutic strategies in the treatment of Alzheimer's disease (AD). Previously we reported compound T5369186 with a core of quinolone as a new cholinesterase inhibitor. In the present study, in order to identify new cores for the designing of AChE inhibitors, we screened different derivatives of this core with the aim to identify the best core as the starting point for further optimization. Based on the results, we confirmed that only 4-aminoquinoline (compound 04 and 07) had cholinesterase inhibitory effects...
2016: PeerJ
Kunnigar Vongnam, Chawanphat Muangnoi, Pornchai Rojsitthisak, Mongkol Sukwattanasinitt, Paitoon Rashatasakhon
Three amidoquinoline-naphthalimide dyads are designed and synthesized in 67-73% overall yields in 3 steps from commercially available starting materials. Compounds with unsubstituted and nitro naphthalimide (1 and 2) show excellent selective fluorescent responses towards glucosamine with the enhancement of fluorescence quantum yields by 14 folds. The determination of HOMO-LUMO levels by linear sweep voltammetry suggests that the sensing mechanism likely involves the inhibition of photo-induced electron transfer (PET) between the aminoquinoline and naphthalimide moieties by glucosamine...
December 15, 2016: Biosensors & Bioelectronics
Thibaut Vausselin, Karin Séron, Muriel Lavie, Ahmed Atef Mesalam, Matthieu Lemasson, Sandrine Belouzard, Lucie Fénéant, Adeline Danneels, Yves Rouillé, Laurence Cocquerel, Lander Foquet, Arielle R Rosenberg, Czeslaw Wychowski, Philip Meuleman, Patricia Melnyk, Jean Dubuisson
UNLABELLED: Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, and some molecules of this family also exhibit antiviral properties. Here we tested several derivatives of 4-aminoquinolines and piperazines for their activity against hepatitis C virus (HCV). We screened 11 molecules from three different families of compounds, and we identified anti-HCV activity in cell culture for six of them. Of these, we selected a compound (B5) that is currently ending clinical phase I evaluation for neurodegenerative diseases...
October 1, 2016: Journal of Virology
Shailja Singh, Drishti Agarwal, Kumkum Sharma, Manish Sharma, Morten A Nielsen, Michael Alifrangis, Ashok K Singh, Rinkoo D Gupta, Satish K Awasthi
Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo...
October 21, 2016: European Journal of Medicinal Chemistry
Jeffrey S Derrick, Richard A Kerr, Kyle J Korshavn, Michael J McLane, Juhye Kang, Eunju Nam, Ayyalusamy Ramamoorthy, Brandon T Ruotolo, Mi Hee Lim
The complex and multifaceted pathology of Alzheimer's disease (AD) continues to present a formidable challenge to the establishment of long-term treatment strategies. Multifunctional compounds able to modulate the reactivities of various pathological features, such as amyloid-β (Aβ) aggregation, metal ion dyshomeostasis, and oxidative stress, have emerged as a useful tactic. Recently, an incorporation approach to the rational design of multipurpose small molecules has been validated through the production of a multifunctional ligand (ML) as a potential chemical tool for AD...
May 16, 2016: Inorganic Chemistry
Rita C C Carvalho, Wagner A Martins, Tayara P Silva, Carlos R Kaiser, Mônica M Bastos, Luiz C S Pinheiro, Antoniana U Krettli, Núbia Boechat
Cerebral malaria is caused by Plasmodium falciparum. Atorvastatin (AVA) is a pentasubstituted pyrrole, which has been tested as an adjuvant in the treatment of cerebral malaria. Herein, a new class of hybrids of AVA and aminoquinolines (primaquine and chloroquine derivatives) has been synthesized. The quinolinic moiety was connected to the pentasubstituted pyrrole from AVA by a linker group (CH2)n=2-4 units. The activity of the compounds increased with the size of the carbons chain. Compound with n=4 and 7-chloroquinolinyl has displayed better activity (IC50=0...
April 15, 2016: Bioorganic & Medicinal Chemistry Letters
Sean Ekins, Joel S Freundlich, Alex M Clark, Manu Anantpadma, Robert A Davey, Peter Madrid
The search for small molecule inhibitors of Ebola virus (EBOV) has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs) with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries...
2015: F1000Research
Supriya Sahu, Surajit Kumar Ghosh, Junmoni Kalita, Mayurakhi Dutta, Hans Raj Bhat
Existing antifolate antimalarial drugs have shown resistance due to the mutations at some amino acid positions of Plasmodium falciparum DHFR-TS. In the present study, to overcome this resistance, a new series of hybrid 4-aminoquinoline-triazine derivatives were designed and docked into the active site of Pf-DHFR-TS (PDB i.d. 1J3K) using validated CDOCKER protocol. Binding energy was calculated by applying CHARMm forcefield. Binding energy and the pattern of interaction of the docked compounds were analysed...
April 2016: Experimental Parasitology
David M Plouffe, Melanie Wree, Alan Y Du, Stephan Meister, Fengwu Li, Kailash Patra, Aristea Lubar, Shinji L Okitsu, Erika L Flannery, Nobutaka Kato, Olga Tanaseichuk, Eamon Comer, Bin Zhou, Kelli Kuhen, Yingyao Zhou, Didier Leroy, Stuart L Schreiber, Christina A Scherer, Joseph Vinetz, Elizabeth A Winzeler
Preventing transmission is an important element of malaria control. However, most of the current available methods to assay for malaria transmission blocking are relatively low throughput and cannot be applied to large chemical libraries. We have developed a high-throughput and cost-effective assay, the Saponin-lysis Sexual Stage Assay (SaLSSA), for identifying small molecules with transmission-blocking capacity. SaLSSA analysis of 13,983 unique compounds uncovered that >90% of well-characterized antimalarials, including endoperoxides and 4-aminoquinolines, as well as compounds active against asexual blood stages, lost most of their killing activity when parasites developed into metabolically quiescent stage V gametocytes...
January 13, 2016: Cell Host & Microbe
Natasa Terzić, Jelena Konstantinović, Mikloš Tot, Jovana Burojević, Olgica Djurković-Djaković, Jelena Srbljanović, Tijana Štajner, Tatjana Verbić, Mario Zlatović, Marta Machado, Inês S Albuquerque, Miguel Prudêncio, Richard J Sciotti, Stevan Pecic, Sarah D'Alessandro, Donatella Taramelli, Bogdan A Šolaja
The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 μM and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P...
January 14, 2016: Journal of Medicinal Chemistry
G Franci, G Manfroni, R Cannalire, T Felicetti, O Tabarrini, A Salvato, M L Barreca, L Altucci, V Cecchetti
OBJECTIVES: A number of previous studies has provided evidence that the well-known anti-bacterial quinolones may have potential as anti-cancer drugs. The aim of this study was to evaluate potential anti-tumour activity and selectivity of a set of 6-aminoquinolones showing some chemical similarity to naphthyridone derivative CX-5461, recently described as innovative anti-cancer agent. MATERIALS AND METHODS: In-house quinolones 1-8 and ad hoc synthesized derivatives 9-13 were tested on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and mesenchymal progenitor (MePR2B) cell lines, analysing their effects on the cell cycle and cell death using FACS methodology...
December 2015: Cell Proliferation
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