Disease relevance of quinolin-4-amine

• OBJECTIVE: To assess the clinical and molecular response of patients with recurrent high-grade vulvar, vaginal, or cervical intraepithelial neoplasia treated with topical 1-2(2-methylpropyl)-1H-imidazo [4,5-c] quinolin-4-amine (imiquimod) cream 5%, an immune response modifier with known efficacy in the treatment of external genital warts [1].
• Amodiaquine (AQ) (2) is a 4-aminoquinoline antimalarial that can cause adverse side effects including agranulocytosis and liver damage [2].
• The 4-aminoquinoline drug hydroxychloroquine (HCQ) is reported to be as active as chloroquine (CQ) against falciparum malaria, and less toxic [3].
• The development and clinical use of 4-aminoquinoline antimalarial agents such as amodiaquine have been limited by toxicity to neutrophils [4].
• These results suggest that certain undetermined factors, present in febrile patients with malaria, predispose to 4-aminoquinoline-induced pruritus [5].

High impact information on quinolin-4-amine

• Dichlorquinazine (alpha 4-aminoquinoline) effective in vitro against chloroquine-resistant Plasmodium falciparum [6].
• However, other reports suggest that 4-aminoquinoline drugs can be taken safely during pregnancy, even in dosages used to control systemic connective tissue diseases [7].
• Two main haplotypes, CVIET and SVMNT, of the Plasmodium falciparum chloroquine-resistance transporter gene (Pfcrt) are linked to 4-aminoquinoline resistance [8].
• The in vitro activity of piperaquine, a new Chinese synthetic drug belonging to the bisquinolines, was evaluated in 103 fresh clinical isolates of P. falciparum in Cameroon, Central Africa, and compared with that of other 4-aminoquinoline and Mannich base derivatives and dihydroartemisinin [9].
• It is a synthetic hybrid that contains the 4-aminoquinoline substructure of one anti-Alzheimer drug, tacrine, and a carbobicyclic moiety resembling that of another AChE inhibitor, (-)-huperzine A [10].

Chemical compound and disease context of quinolin-4-amine

• Mutagenic activities of 4-aminopyridine (4AP), 4-aminoquinoline (4AQ), 9-aminoacridine (9AA) and harman (HM) were examined by the Salmonella test system in the presence of cobalt(II) chloride (CoCl2), which itself is non-mutagenic in this system [11].
• Hydroxychloroquine (HCQ) is a 4-aminoquinoline antimalarial drug used for the treatment of autoimmune diseases [12].

Biological context of quinolin-4-amine

• Structure-activity relationships in 4-aminoquinoline antiplasmodials. The role of the group at the 7-position [13].
• No DNA damage was induced by the noncarcinogenic 4-aminoquinoline 1-oxide (4AQO) [14].
• 4-Aminoquinoline antimalarials enhance UV-B induced c-jun transcriptional activation [15].
• Effects of 4-aminoquinoline on action potentials of the frog sinus venosus [16].
• Pharmacokinetics and cellular uptake of 4-aminoquinoline antimalarials [17].

Anatomical context of quinolin-4-amine

• Slow m.e.p.p.s were induced in vivo by paralysing the extensor digitorum longus muscle of the rat with botulinum toxin type A or in vitro by the application of 4-aminoquinoline to the mouse diaphragm nerve-muscle preparation [18].
• Differential effects of 4-aminoquinoline-containing antimalarial drugs on hemoglobin digestion in Plasmodium falciparum-infected erythrocytes [19].
• Examination of spontaneous miniature endplate potentials (MEPPs) in murine skeletal muscle has revealed that in conditions such as botulinum poisoning, during nerve terminal regeneration or in the presence of the drug 4-aminoquinoline, two types of acetylcholine release are responsible for the MEPPs [20].
• The prodrugs were prepared by linking bioreversibly a GR inhibitor to a 4-aminoquinoline moiety which is known to concentrate in the acidic food vacuole of parasites [21].
• The 4-aminoquinoline antimalarial drugs also provide effective treatment, possibly by lysis of affected liver cells [22].

Associations of quinolin-4-amine with other chemical compounds

• Tebuquine (5) is a 4-aminoquinoline that is significantly more active than amodiaquine (2) and chloroquine (1) both in vitro and in vivo [23].
• The 4-aminoquinoline chloroquine and its analogue hydroxychloroquine are endowed with anti-HIV-1 activity both in vitro and in vivo [24].
• Two markers for 4-aminoquinoline resistance, P. falciparum chloroquine resistance transporter 76T and P. falciparum multidrug resistance 1, were fixed in the population and two markers for pyrimethamine resistance, dihydrofolate reductase (dhps) 59R and 108N, were found at moderate to high levels, overall 60% and 75%, respectively [25].
• A new class of 4-aminoquinoline derivatives based on the natural product isatin scaffold were designed and synthesized for biological evaluation against three strains of the malaria parasite Plasmodium falciparum [26].
• Three series of 4-aminopyridine-and 4-aminoquinoline based symmetrical bivalent acetylcholinesterase (AChE) inhibitors were prepared and compared to previously synthesized dimers of 9-amino-1,2,3,4-tetrahydroacridine (tacrine) [27].

Gene context of quinolin-4-amine

• To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized [28].
• The 4-aminoquinoline radical containing antimalarial drugs are also used in the management of various connective tissue diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis [29].
• Screening of the Roche compound library led to the identification of 4-aminoquinoline 4 as structurally novel NR1/2B subtype selective NMDA receptor antagonist [30].

Analytical, diagnostic and therapeutic context of quinolin-4-amine

• However, it was concluded that BoTx m.e.p.p.s do not originate from the Schwann cells because denervation of BoTx-paralysed frogs abolishes all m.e.p.p.s and the drug 4-aminoquinoline affects BoTx m.e.p.p.s and Schwann m.e.p.p.s in opposite ways, increasing the frequency of the former while almost eliminating the latter [31].
• The electrophysiological effects of 4-aminoquinoline (4-AQ), a drug structurally related to 4-aminopyridine, were studied on the sinus venosus of the frog Caudiverbera caudiverbera with standard microelectrode techniques [16].

References