5407-57-8Relevant articles and documents
Application of multi-component reactions to antimalarial drug discovery. Part 1: Parallel synthesis and antiplasmodial activity of new 4-aminoquinoline Ugi adducts
Musonda, Chitalu C.,Taylor, Dale,Lehman, Julie,Gut, Jiri,Rosenthal, Philip J.,Chibale, Kelly
, p. 3901 - 3905 (2004)
The synthesis of a new class of Ugi adducts incorporating the 4-aminoquinoline moiety is described. The novel compounds are active against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with the best compound showing
Design, synthesis and antiplasmodial activity of novel imidazole derivatives based on 7-chloro-4-aminoquinoline
Kondaparla, Srinivasarao,Manhas, Ashan,Dola, Vasantha Rao,Srivastava, Kumkum,Puri, Sunil K.,Katti
, p. 204 - 211 (2018)
A series of short chain 4-aminoquinoline-imidazole derivatives have been synthesized in one pot two step multicomponent reaction using van leusen standard protocol. The diethylamine function of chloroquine is replaced by substituted imidazole derivatives containing tertiary terminal nitrogen. All the synthesized compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (K1) strains of Plasmodium falciparum. Some of the compounds (6, 8, 9 and 17) in the series exhibited comparable activity to CQ against K1 strain of P. falciparum. All the compounds displayed resistance factor between 0.09 and 4.57 as against 51 for CQ. Further, these analogues were found to form a strong complex with hematin and inhibit the β-hematin formation, therefore these compounds act via heme polymerization target.
Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain
Iwaniuk, Daniel P.,Whetmore, Eric D.,Rosa, Nicholas,Ekoue-Kovi, Kekeli,Alumasa, John,de Dios, Angel C.,Roepe, Paul D.,Wolf, Christian
, p. 6560 - 6566 (2009)
We report the synthesis and in vitro antimalarial activity of several new 4-amino- and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of Plasmodium falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11-15 and 24 proved to be more potent against Dd2 than chloroquine. Branching of the side chain structure proved detrimental to the activity against the CQR strain.
Synthesis and preliminary biological evaluation of a small library of hybrid compounds based on Ugi isocyanide multicomponent reactions with a marine natural product scaffold
Avilés, Edward,Prudhomme, Jacques,Le Roch, Karine G.,Franzblau, Scott G.,Chandrasena, Kevin,Mayer, Alejandro M.S.,Rodríguez, Abimael D.
, p. 5339 - 5343 (2015)
A mixture-based combinatorial library of five Ugi adducts (4-8) incorporating known antitubercular and antimalarial pharmacophores was successfully synthesized, starting from the naturally occurring diisocyanide 3, via parallel Ugi four-center three-compo
Synthesis and biological activity of novel 4-aminoquinoline/1,2,3-triazole hybrids against Leishmania amazonensis
Glanzmann, Nícolas,Antinarelli, Luciana Maria Ribeiro,da Costa Nunes, Isabelle Karine,Pereira, Henrique Marcelo Gualberto,Coelho, Eduardo Antonio Ferraz,Coimbra, Elaine Soares,da Silva, Adilson David
, (2021)
Quinoline and 1,2,3-triazoles are well-known nitrogen-based heterocycles presenting diverse pharmacological properties, although their antileishmanial activity is still poorly exploited. As an effort to contribute with studies involving these interesting chemical groups, in the present study, a series of compounds derived from 4-aminoquinoline and 1,2,3-triazole were synthetized and biological studies using L. amazonensis species were performed. The results pointed that the derivative 4, a hybrid of 4-aminoquinoline/1,2,3-triazole exhibited the best antileishmanial action, with inhibitory concentration (IC50) values of ~1 μM against intramacrophage amastigotes of L. amazonensis, and being 16-fold more active to parasites than to the host cell. The mechanism of action of derivative 4 suggest a multi-target action on Leishmania parasites, since the treatment of L. amazonensis promastigotes caused mitochondrial membrane depolarization, accumulation of ROS products, plasma membrane permeabilization, increase in neutral lipids, exposure of phosphatidylserine to the cell surface, changes in the cell cycle and DNA fragmentation. The results suggest that the antileishmanial effect of this compound is primarily altering critical biochemical processes for the correct functioning of organelles and macromolecules of parasites, with consequent cell death by processes related to apoptosis-like and necrosis. No up-regulation of reactive oxygen and nitrogen intermediates was promoted by derivative 4 on L. amazonensis -infected macrophages, suggesting a mechanism of action independent from the activation of the host cell. In conclusion, data suggest that derivative 4 presents selective antileishmanial effect, which is associated with multi-target action, and can be considered for future studies for the treatment against disease.
Property-Based Design and Synthesis of New Chloroquine Hybrids via Simple Incorporation of 2-Imino-thiazolidin-4-one or 1H-Pyrrol-2,5-dione Fragments on the 4-Amino-7-chloroquinoline Side Chain
Rojas, Fernando A.,Kouznetsov, Vladimir V.
, p. 1774 - 1781 (2011)
In the present work, the syntheses of new 4-amino-7-chloroquinoline N-derivatives were performed by selective modification of the side chain amino group of N-(7-chloroquinolin-4-yl)alkyldiamines, basis framework of chloroquine (CQ) drug through the incorporation of heterocyclic 2-imino-thiazolidin-4-one and 1H-pyrrol-2,5-dione systems. These potential activity modulators were selected thanks to their characteristic properties, and evaluated by virtual screening employing the OSIRIS and Molinspirations platforms. Designed and synthesized quinolinic derivatives could increase the antimalarial activity of CQ analogues without affecting the lipophilicity as described in literature, suggesting them as candidates for further biological assessments. ?2011 Sociedade Brasileira de Qui?mica.
Synthesis, antimalarial activity, heme binding and docking studies of N-substituted 4-aminoquinoline-pyrimidine molecular hybrids
Maurya, Shiv Shyam,Khan, Shabana I.,Bahuguna, Aparna,Kumar, Deepak,Rawat, Diwan S.
, p. 175 - 185 (2017)
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. The interaction of these hybrids was also investigated by the molecular docking studies in the binding site of wild type Pf-DHFR-TS and quadruple mutant Pf-DHFR-TS. The pharmacokinetic property analysis of best active compounds was also studied by ADMET prediction.
Synthesis, Cytotoxicity, Molecular Docking, Molecular Simulation and ADME Properties of Cinnamoylated Chloroquine Hybrid Analogues as Corona Virus Protease Inhibitors
Hemapriya, K.,Jayanthi, K. R.,Ravi, Subban
, p. 163 - 171 (2022/03/16)
In an attempt to challenge COVID-19, molecular docking of cinnamoylated chloroquine compounds 1–15 against main protease (Mpro) enzyme of SARS-CoV-2 was undertaken. To study the stability of the complex formed between the drug and the receptor, suitable docking possesses were selected and put into molecular dynamics studies. Further ADME properties were determined using SWISS ADME software. In the docking studies compounds 5, 9, 14 and 15 exhibited encouragable binding with the Mpro crystal structure with docking scores of -8.1, -7.9, -7.8 and -7.9 Kcal/mole respectively. It was observed that CYS145 and GLU166 played a significant role during the interaction of molecules with the active site of COVID-19 Mpro. Among compounds 5, 9, 14 and 15, compound 5 had stable interactions with the protein, which might be the reason for the optimum RMSD, RMSF, radius of gyration and protein–ligand contacts (hydrogen bonding) values. The compound 5 was synthesised and tested for its cytotoxic activity against fibroblast L929 cell line. The above study indicated that the compound 5 as a promising agent, and during the drug discovery process it could be taken as a starting point for lead optimization.
Anti-SARS-CoV-2 Inhibitory Profile of New Quinoline Compounds in Cell Culture-Based Infection Models
Herrmann, Lars,Hahn, Friedrich,Wangen, Christina,Marschall, Manfred,Tsogoeva, Svetlana B.
supporting information, (2022/01/06)
The presently ongoing pandemic of human SARS-CoV-2 infections (COVID-19) presents an enormous challenge in surveillance, vaccine and antiviral drug development. Here we report the synthesis of new bioactive quinoline-morpholine hybrid compounds and their
