Quinacrine: Mechanisms of Antimalarial Action

Dyke, Knox Van; Lantz, C.H.; Szustkiewicz, C.

doi:10.1126/science.169.3944.492

Cited by 41 publications

(17 citation statements)

References 19 publications

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“…The interaction of QA (Fig. 1 ) with DNA was firstly reported by Van Dyke et al [54]. They observed yellow-green fluorescence in nuclei of parasite P. falciparum in the presence of that acridine.…”

Section: Mechanisms Of Antimalarial Activitysupporting

confidence: 52%

Acridine and Acridinones: Old and New Structures with Antimalarial Activity

Valdés¹

2011

Open Med Chem J

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Since emergence of chloroquine-resistant Plasmodium falciparum and reports of parasite resistance to alternative drugs, there has been renewed interest in the antimalarial activity of acridines and their congeners, the acridinones. This article presents literature compilation of natural acridinone alkaloids and synthetic 9-substituted acridines, acridinediones, haloalcoxyacridinones and 10-N-substituted acridinones with antimalarial activity. The review also provides an outlook to antimalarial modes of action of some described compounds.

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Section: Mechanisms Of Antimalarial Activitysupporting

confidence: 52%

Acridine and Acridinones: Old and New Structures with Antimalarial Activity

Valdés¹

2011

Open Med Chem J

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“…Vinblastine (NSC49842) is used in the treatment of Hodgkin’s lymphoma [37], and in combination with cisplatin and bleomycin in the treatment of testicular and ovarian germ cell cancers [38]. Mepacrine (quinacrine, NSC14229), an inhibitor of NFκB [39] and topoisomerase activity [40], is primarily used as an antimalarial drug [41]. In oncology, it is most commonly used for the treatment of pleural effusions in advanced malignant diseases [42].…”

Section: Resultsmentioning

confidence: 99%

Identification of inhibitors of ovarian cancer stem-like cells by high-throughput screening

2012

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BackgroundOvarian cancer stem cells are characterized by self-renewal capacity, ability to differentiate into distinct lineages, as well as higher invasiveness and resistance to many anticancer agents. Since they may be responsible for the recurrence of ovarian cancer after initial response to chemotherapy, development of new therapies targeting this special cellular subpopulation embedded within bulk ovarian cancers is warranted.MethodsA high-throughput screening (HTS) campaign was performed with 825 compounds from the Mechanistic Set chemical library [Developmental Therapeutics Program (DTP)/National Cancer Institute (NCI)] against ovarian cancer stem-like cells (CSC) using a resazurin-based cell cytotoxicity assay. Identified sets of active compounds were projected onto self-organizing maps to identify their putative cellular response groups.ResultsFrom 793 screening compounds with evaluable data, 158 were found to have significant inhibitory effects on ovarian CSC. Computational analysis indicates that the majority of these compounds are associated with mitotic cellular responses.ConclusionsOur HTS has uncovered a number of candidate compounds that may, after further testing, prove effective in targeting both ovarian CSC and their more differentiated progeny.

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“…Although reports (16,48) (44), increases antibody production (3), increases interferon synthesis (32), and inhibits tumors (4,45 (21,39,46), the primary action (or characteristic side effects of these compounds) may stem from responses activated in host or pathogen rather than exclusively from the biocidal effects on the pathogen (19).…”

Section: Resulttsmentioning

confidence: 99%

Specificity of Deoxyribonucleic Acid Intercalating Compounds in the Control of Phenylalanine Ammonia Lyase and Pisatin Levels

Hadwiger

Schwochau

1971

Plant Physiol.

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Compounds with planar triple ring systems such as acridine orange, 9-amino acridine, 9-amino-1,2,3, 4-tetrahydroacridine (tacrine), 6,9-diamino-2-ethoxyacridine lactate monohydrate (DE-acridine), 6-chloro-9-(3'-diethylamino-2'-hydroxypropylamino)-2-methoxyacridine 2 HCI (CDM-acridine), quinacrine, 6-chloro-9-(4'-diethylamino-1'-methylbutylamino) .2-methoxy. 1, 10-diazaanthracene (CDM 1, 10-diazaanthracene), thionine, azure A, methylene blue, and pyronine Y when applied to excised pea pods were potent inducers of phenylalanine ammonia lyase or of pisatin, or of both. Compounds with an array of structural variation around the planar three-ring system were tested for their ability to induce these responses in pea tissue. In general, dimethylamino, diethylamnino, or amino substitutions at position 2 and 6 or an amino (with or without an aliphatic side chain) substitution at position 9 of the three-ring system augmented induction potential. Methyl green, methylene blue, 2, 7-diaminofluorene, nile blue, neutral red, pyrogallol red, ethidium bromide, nogalamycin, quinine, chloroquine, spermine, 8-azaguanine, gliotoxin, chromomycin A3, actinomycin D, and mitomycin C were also potent inducers.The inhibition of phenylalanine ammonia lyase induction by the application of actinomycin D (300 micrograms per milliliter) or 6-methylpurine (1 milligram per milliliter) within 1 hour after inducer application indicated that newly synthesized RNA is necessary for induction. Phenylalanine ammonia lyase induction was also inhibited by cycloheximide (150 micrograms per milliliter).Various chemicals with the potential to intercalate into DNA molecules have been used extensively to study DNA structure and mutagenic, antiviral, antimitotic, anticarcinogenic, antimalarial activity (1,30,37,48 Methods. Experiments quantitating pisatin production and PAL activity utilized 1 g of fresh immature pea pods (1-2 cm long, harvested while still enclosed in the blossom). The general procedure, which involved splitting the pods and administering 1.5 ml of the aqueous solutions of the inducer compounds to the exposed pea endocarp, has been described in detail previously (41).Standardized methods for the isolation and quantitation of pisatin (41)

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Quinacrine: Mechanisms of Antimalarial Action

Cited by 41 publications

References 19 publications

Acridine and Acridinones: Old and New Structures with Antimalarial Activity

Acridine and Acridinones: Old and New Structures with Antimalarial Activity

Identification of inhibitors of ovarian cancer stem-like cells by high-throughput screening

Specificity of Deoxyribonucleic Acid Intercalating Compounds in the Control of Phenylalanine Ammonia Lyase and Pisatin Levels

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