4-Aminoquinoline Compound

BACKGROUND: Polypharmacology means drugs having interactions with multiple targets of a unique disease or many disease pathways. This concept has been greatly appreciated against complex diseases, such as oncology, CNS disorders, and anti-infectives. METHODS: The integration of diverse compounds available on public databases initiates polypharmacological drug discovery research. Immunocompromised patients may suffer from complex diseases. Multiple-component drug formulations may produce side effects and resistance issues due to unintended drug-target interactions...

In this study, new 7-chloro-4-aminoquinoline-benzimidazole compounds were synthesized and characterized by NMR, MS, and elemental analysis. These novel hybrids differ in the type of linker and in the substituent on the benzimidazole moiety. Their antiproliferative activities were evaluated on one non-tumor (MDCK1) and seven selected tumor (CaCo-2, MCF-7, CCRF-CEM, Hut78, THP-1, and Raji) cell lines by MTT test and flow cytometry analysis. The compounds with different types of linkers and an unsubstituted benzimidazole ring, 5d , 8d , and 12d, showed strong cytotoxic activity (the GI50 ranged from 0...

Herein a series of 4-aminoquinolines were synthesized in an attempt to optimize and study the structural features related to LABIO-17 biological activity, a Mycobacterium tuberculosis NADH-dependent enoyl-acyl carrier protein reductase (MtInhA) inhibitor previously identified by a virtual-ligand-screening approach. Structure-activity relationships led to novel submicromolar inhibitors of MtInhA and potent antitubercular agents. The lead compound is 87-fold more potent as enzymatic inhibitors and 32-fold more potent against M...

A library of quinoline-based hydrazones bearing 1H-1,2,3-triazole core was designed, synthesized and evaluated for their antiplasmodial activity against the drug-resistant Plasmodium falciparum W2 strain. The inclusion of pyrazine-2-carboxylic acid with a flexible propyl spacer afforded the most active scaffold with an IC50 value of 0.26 μM. Mechanistically, the compound inhibited heme to hemozoin formation, as demonstrated by UV-vis and mass spectral studies.

Receptor-interacting protein kinase 2 (RIPK2) is an essential protein kinase mediating signal transduction by NOD1 and NOD2, which play an important role in regulating immune signalling. In this study, we designed and synthesised a novel series of 4-aminoquinoline-based derivatives as RIPK2 inhibitors. In vitro , compound 14 exhibited high affinity (IC50 = 5.1 ± 1.6 nM) and excellent selectivity to RIPK2 showing in a dendrogram view of the human kinome phylogenetic tree. Bearing favourable lipophilicity and eligible lipophilic ligand efficiency (LipE), compound 14 was selected to investigate cellular anti-inflammatory effect and was identified as a potent inhibitor to reduce the secretion of MDP-induced TNF-α with a dose-dependent manner...

BACKGROUND: Amodiaquine is a 4-aminoquinoline used extensively for the treatment and prevention of malaria. Orally administered amodiaquine is largely converted to the active metabolite desethylamodiaquine. Amodiaquine can cause bradycardia, hypotension, and electrocardiograph (ECG) QT interval prolongation but the relationship of these changes to drug concentrations is not well-characterised. METHODS: We conducted a secondary analysis of a pharmacokinetic study of the cardiac safety of amodiaquine (10mg base/kg/day over 3 days) in 54 Kenyan adults (≥18 years) with uncomplicated malaria...

A series of novel 4- N -phenylaminoquinoline derivatives containing a morpholine group were designed and synthesized, and their anti-cholinesterase activities and ABTS radical-scavenging activities were tested. Among them, compounds 11a, 11g , 11h , 11j , 11l, and 12a had comparable inhibition activities to reference galantamine in AChE. Especially, compound 11g revealed the most potent inhibition on AChE and BChE with IC50 values of 1.94 ± 0.13 μM and 28.37 ± 1.85 μM, respectively. The kinetic analysis demonstrated that both the compounds 11a and 11g acted as mixed-type AChE inhibitors...

Quick and precise recovery of palladium (Pd) from electronic waste remains a serious task, owing to the strong acid and complexity of chemical compounds in leachate. Here, bioinspired construction of magnetic nano stirring rod with radially aligned dual mesopores and abundant 8-aminoquinoline (MNSR-DM-AQ) is proposed for selective and rapid extraction of Pd(II) from highly acidic sample solutions. Benefit from the unique dual mesoporous (12.4 nm and 3.6 nm) and the stirring motion under an external magnetic field, MNSR-DM-AQ possesses enhanced adsorption capacity and kinetics, achieving 11...

In the search of new antiplasmodial agents, a multitargeted approach was used in the synthesis of triazolopyrimidine- and 4-aminoquinolines-based hybrids. In vitro antiplasmodial evaluation on chloroquine-sensitive (3D7) and -resistant (W2) P. falciparum strains identified triazolopyrimidine-4-aminoquinoline hybrids to be the most potent in the series, outperforming bis-triazolopyrimidines. The active compounds were subjected to mechanistic studies with the plausible and expected targets including heme, PfCRT, and PfDHODH, that eventually validated the biological data...

The azo-coupling reaction between 8-aminoquinoline and 3,5-dimethoxyphenol produces 2,6-dimethoxycyclohexa-2,5-diene-1,4-dione 1-[2-(quinolin-8-yl)hydrazone], C17 H15 N3 O3 . Crystallization from methanol and strong alkaline solutions produced nonsolvated and solvated crystals, respectively. The crystal structure analysis and 1 H NMR spectroscopy studies revealed that the compound exists only as the hydrazone form. A UV-Vis spectroscopic titration study revealed that the hydrazone compound has a relatively high pKa value of 10...

Aiming to discover novel antifungal agents, a series of 2‑substituted‑4‑amino-quinolines and -quinazoline were prepared and characterized using IR, 1 H NMR, 13 C NMR, and HRMS spectroscopic techniques. Their antifungal activities against four invasive fungi were evaluated, and the results revealed that some of the target compounds exhibited moderate to excellent inhibitory potencies. The most promising compounds III11 , III14 , III15, and III23 exhibited potent and broad-spectrum antifungal activities with MIC values of 4-32 μg/mL...

Considering that acetylcholinesterase (AChE) inhibition is the most important mode of action expected of a potential drug used for the treatment of symptoms of Alzheimer's disease (AD), our previous pilot study of 4-aminoquinolines as potential human cholinesterase inhibitors was extended to twenty-two new structurally distinct 4-aminoquinolines bearing an adamantane moiety. Inhibition studies revealed that all of the compounds were very potent inhibitors of AChE and butyrylcholinesterase (BChE), with inhibition constants ( Ki ) ranging between 0...

Chloroquine (CQ) and hydroxychloroquine (HCQ) have long been used worldwide to treat and prevent human malarias. However, these 4-aminoquinolines have also shown promising potential in treating chronic illnesses with an inflammatory component, including neurological diseases. Given the current demand for serum avoidance during pharmacological testing and modeling of some pathologies, we compared cytotoxicities of CQ and HCQ in both serum-deprived and -fed murine BV-2 microglia. Furthermore, we assessed the anti-neuroinflammatory potential of both compounds in serum-deprived cells...

There is a wide variety of neurodegenerative diseases, among which frontotemporal dementia stands out. These are the second most frequent cause of dementia in the world and demand the search for an effective treatment. This disease is linked to the abnormal behavior of proteins, which group together to form insoluble aggregates. It has been shown that the tau protein and TDP-43 are the main proteins involved in these pathologies. This article details 11 compounds already used in different neuropathologies, which may serve as potential drugs against these proteins...

Acetylcholinesterase (AChE) has proven to be an effective drug target in the treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's and dementia. We developed a novel QSAR regression model for estimating potency to inhibit AChE, p K i , on a set of 75 structurally different compounds including oximes, N-hydroxyiminoacetamides, 4-aminoquinolines and flavonoids. Although the model included only three simple descriptors, the valence molecular connectivity index of the zero-order, 0 χv , the number of 10-membered rings (nR10) and the number of hydroxyl groups (nOH), it yielded excellent statistics ( r  = 0...

Tuberculosis remains a global health problem that affects millions of people around the world. Despite recent efforts in drug development, new alternatives are required. Herein, a series of 27 N -(4-(benzyloxy)benzyl)-4-aminoquinolines were synthesized and evaluated for their ability to inhibit the M. tuberculosis H37Rv strain. Two of these compounds exhibited minimal inhibitory concentrations (MICs) similar to the first-line drug isoniazid. In addition, these hit compounds were selective for the bacillus with no significant change in viability of Vero and HepG2 cells...

Background: Alzheimer's disease (AD) is thought to be a complex, multifactorial syndrome with many related molecular lesions contributing to its pathogenesis. Thus, multi-target-directed ligands are considered an effective way of treating AD. This study sought to evaluate 8-aminoquinoline-melatonin derivatives as effective multifunctional agents for AD. Methods: Thioflavin-T fluorescence assays were used to detect the inhibitory potency of 8-aminoquinoline-melatonin hybrids (a1-a5, b1-b5, and c1-c5) on self- and acetylcholinesterase (AChE)-induced amyloid-β (Aβ) aggregation...

This paper reports a series of nine hybrid compounds of 7-substituted-4-aminoquinoline and cinnamic acid as antiplasmodial agents. 1 H-NMR and 13 C-NMR spectroscopic analysis and mass spectrometry studies were used to confirm the structures. The synthesized compounds were moderately active, with IC50 values ranging from 1.8 to 16 µM against the Pf3D7 chloroquine sensitive strain in vitro. Compound C11 showed to be the most potent in this investigation, with an IC50 value of 1.8 µM. Molecular docking studies revealed that compounds C14 and C17, with binding energies (ΔG°) of -7...

In the search for new anti-HIV-1 agents, two forms of phenylamino-phenoxy-quinoline derivatives have been synthesized, namely, 2-phenylamino-4-phenoxy-quinoline and 6-phenylamino-4-phenoxy-quinoline. In this study, the binding interactions of phenylamino-phenoxy-quinoline derivatives and six commercially available drugs (hydroxychloroquine, ritonavir, remdesivir, S-217622, N3, and PF-07321332) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro ) were investigated using molecular docking and the ONIOM method...

With its strong effect on vector-borne diseases, and insecticidal effect on mosquito vectors of malaria, inhibition of sporogonic and blood-stage development of Plasmodium falciparum, as well as in vitro and in vivo impairment of the P. berghei development inside hepatocytes, ivermectin (IVM) continues to represent an antimalarial therapeutic worthy of investigation. The in vitro activity of the first-generation IVM hybrids synthesized by appending the IVM macrolide with heterocyclic and organometallic antimalarial pharmacophores, against the blood-stage and liver-stage infections by Plasmodium parasites prompted us to design second-generation molecular hybrids of IVM...