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4-Aminoquinoline Compound

Shiv Shyam Maurya, Shabana I Khan, Aparna Bahuguna, Deepak Kumar, Diwan S Rawat
A series of novel N-substituted 4-aminoquinoline-pyrimidine hybrids have been synthesized via simple and economic route and evaluated for their antimalarial activity. Most compounds showed potent antimalarial activity against both CQ-sensitive and CQ-resistant strains with high selectivity index. All the compounds were found to be non-toxic to the mammalian cell lines. The most active compound 7b was analysed for heme binding activity using UV-spectrophotometer. Compound was found to interact with heme and a complex formation between compound and heme in a 1:1 stoichiometry ratio was determined using job plots...
February 15, 2017: European Journal of Medicinal Chemistry
Saulo Fehelberg Pinto Braga, Luan Carvalho Martins, Elany Barbosa da Silva, Policarpo Ademar Sales Júnior, Silvane Maria Fonseca Murta, Alvaro José Romanha, Wai Tuck Soh, Hans Brandstetter, Rafaela Salgado Ferreira, Renata Barbosa de Oliveira
Analogues of 8-chloro-N-(3-morpholinopropyl)-5H-pyrimido[5,4-b]indol-4-amine 1, a known cruzain inhibitor, were synthesized using a molecular simplification strategy. Five series of analogues were obtained: indole, pyrimidine, quinoline, aniline and pyrrole derivatives. The activity of the compounds was evaluated against the enzymes cruzain and rhodesain as well as against Trypanosoma cruzi amastigote and trypomastigote forms. The 4-aminoquinoline derivatives showed promising activity against both enzymes, with IC50 values ranging from 15 to 125µM...
February 9, 2017: Bioorganic & Medicinal Chemistry
P Linga Reddy, Shabana I Khan, Prija Ponnan, Mohit Tripathi, Diwan S Rawat
A novel series of 4-aminoquinoline-purine hybrids were synthesized and assessed for their antiplasmodial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. It was envisaged that linking of the 4-aminoquinoline pharmacophore (targeting heme-detoxification pathway of malarial parasite) with the purine functionality (targeting plasmodial HG(X)PRT enzyme) will produce a hybrid antiplasmodial agent with increased potency. The synthesized hybrids displayed good antiplasmodial activities against both the sensitive and resistant strains of P...
January 27, 2017: European Journal of Medicinal Chemistry
Srinivasarao Kondaparla, Awakash Soni, Ashan Manhas, Kumkum Srivastava, Sunil K Puri, S B Katti
In the present study we have synthesized a new class of 4-aminoquinolines and evaluated against Plasmodium falciparum in vitro (3D7-sensitive strain & K1-resistant strain) and Plasmodium yoelii in vivo (N-67 strain). Among the series, eleven compounds (5, 6, 7, 8, 9, 11, 12, 13, 14, 15 and 21) showed superior antimalarial activity against K1 strain as compared to CQ. In addition, all these analogues showed 100% suppression of parasitemia on day 4 in the in vivo mouse model against N-67 strain when administered orally...
November 23, 2016: Bioorganic Chemistry
Srinivasarao Kondaparla, Pooja Agarwal, Kumkum Srivastava, Sunil K Puri, Seturam B Katti
A series of novel bisquinoline compounds comprising N(1) -(7-chloroquinolin-4-yl) ethane-1,2-diamine and 7-chloro-N-(2-(piperazin-1-yl)ethyl)quinolin-4-amine connected with 7-chloro-4-aminoquinoline containing various amino acids is described. We have bio-evaluated the compounds against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum in vitro. Among the series, compounds 4 and 7 exhibited 1.8- and 10.6-fold superior activity as compared to chloroquine (CQ; IC50  = 0...
November 29, 2016: Chemical Biology & Drug Design
Filip Křemen, Martin Gazvoda, Stanislav Kafka, Karel Proisl, Anna Srholcová, Antonin Klasek, Damijana Urankar, Janez Košmrlj
An unprecedented reactivity of 3-aminoquinoline-2,4-diones is reported. Under basic conditions these compounds undergo molecular rearrangement to furnish 1,4-benzodiazepine-2,5-diones. The transformations take place under mild reaction conditions by using 1,1,3,3-tetramethylguanidine (TMG), NaOEt, or benzyltrimethylammonium hydroxide (Triton B) as a base. A proposed mechanism of the rearrangement and the conformational equilibrium of 1,4-benzodiazepine-2,5-dione rings are discussed.
October 27, 2016: Journal of Organic Chemistry
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...
December 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.
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 remains 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 Plasmodium falciparum In most cases, the metabolic profiles were highly correlated with known antimalarials, in particular artemisinin, the 4-aminoquinolines, or atovaquone...
November 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...
December 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...
July 27, 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
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