Structure-activity relationships and inhibitory effects of various purine derivatives on the in vitro growth of Plasmodium falciparum11Abbreviations: CDK, cyclin-dependent kinase; CDK1, cyclin-dependent kinase 1; and PfPK, Plasmodium falciparum protein kinase.

Harmse, Leonie; Zyl, Robyn L. van; Gray, Nathanael S.; Schultz, Peter G.; Leclerc, Sophie; Meijer, Laurent; Doerig, Christian; Havlík, I.

doi:10.1016/s0006-2952(01)00644-x

Cited by 52 publications

(25 citation statements)

References 21 publications

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“…In order to introduce structural diversity within the amino side chain, aziridines 1 were connected to different classes of aromatic azaheterocycles such as adenine [44], thymine and 1,2,4-triazole en route to the corresponding 2-(aminomethyl)aziridines 2a-h (Scheme 1, Table 1). In addition, also diethylamine was used for the preparation of 2-(N,Ndiethylaminomethyl)aziridines 2i-k in order to evaluate the difference between the presence of an aromatic azaheterocyclic moiety and a simple acyclic amino group in 1,2,3-triaminopropanes with regard to their biological activity.…”

Section: Results and Discussion -Synthesismentioning

confidence: 99%

Synthesis of 2-(aminomethyl)aziridines and their microwave-assisted ring opening to 1,2,3-triaminopropanes as novel antimalarial pharmacophores

D’hooghe

Kenis

Vervisch

et al. 2011

European Journal of Medicinal Chemistry

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A variety of 2-(aminomethyl)aziridines was prepared and converted into the corresponding 1,2,3-triaminopropanes through a novel, microwave-assisted and regioselective ring opening by diethylamine in acetonitrile. Antiplasmodial assays revealed antimalarial activity for 2-[(1,2,4-triazol-1-yl)methyl]aziridines and 2-(N,N-diethylaminomethyl)aziridines, as well as for the corresponding 1-(diethylamino)propanes obtained through ring opening, pointing to the relevance of both the 2-(aminomethyl)aziridine and the 1,2,3-triaminopropane unit as novel antimalarial pharmacophores.

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Section: Results and Discussion -Synthesismentioning

confidence: 99%

Synthesis of 2-(aminomethyl)aziridines and their microwave-assisted ring opening to 1,2,3-triaminopropanes as novel antimalarial pharmacophores

D’hooghe

Kenis

Vervisch

et al. 2011

European Journal of Medicinal Chemistry

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“…Since aminopurvalanol A inhibits parasite growth, CK1 inhibitors are potential leads for antiparasitic agents. Interestingly, the cell-impermeable purvalanol B displays activity against P. falciparum [66], and affinity chromatography on the immobilised inhibitor identified PfCK1 as a putative target [67]. The inhibitors tri-substituted pyrrole and imidazopyrine exhibit in vivo efficacy against PKG in Eimeria tenella in chickens and T. gondii in mice, but also inhibit apicomplexan CDPK1 and CK1 [68].…”

Section: The Ck1 Groupmentioning

confidence: 99%

The kinomes of apicomplexan parasites

Miranda‐Saavedra

Gabaldón

Barton

et al. 2012

Microbes and Infection

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Protein phosphorylation plays a fundamental role in the biology and invasion strategies of apicomplexan parasites. Many apicomplexan protein kinases are substantially different from their mammalian orthologues, and thus constitute a landscape of potential drug targets. Here, we integrate genomic, biochemical, genetic and evolutionary information to provide an integrated and up-to-date analysis of twelve apicomplexan kinomes. All kinome sequences are available through the Kinomer database.2

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“…These are known to inhibit growth of human tumour cell lines [42], but one of them, purvalanol B specifically prevented parasite growth in the low micromolar range [43]. This highly potent CDK inhibitor does not affect human cell lines because of the presence of a carboxyl group, preventing its entry into the cell.…”

Section: Protein Kinase Inhibitorsmentioning

confidence: 99%

The Use of Anticancer Drugs in Antiparasitic Chemotherapy

Klinkert¹,

Heussler

2006

MRMC

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Though the selection and administration of cytotoxic drugs is usually restricted to specialist units, all doctors should be aware of both the available treatment and its associated problems. This review concerns new cytotoxic drugs and some new applications of current drugs. It is largely confined to drugs marketed in the United Kingdom in the past five years and drugs from abroad that are currently used in the United Kingdom, although some mention is made of those still undergoing clinical trial which may be more widely used in the future. Many new drugs are analogues: they are the product of a search for a compound related to an existing cytotoxic drug that will retain or surpass its efficacy with a simultaneous reduction in toxicity. Current drugs and their analogues ALKYLATING AGENTS Alkylating agents-for instance, busulphan, cyclophospha-mide, melphalan, and mustine-prevent replication of nucleic acids by cross linking base pairs. Doses of all alkylating agents are limited by myelosuppression and gastrointestinal disturbance; haemorrhagic cystitis is dose limiting for cyclophosphamide. ANALOGUES OF ALKYLATING AGENTS Ifosfamide (Mitoxana) is structurally related to cyclophos-phamide. It may have better activity against non-small cell lung cancer and soft tissue sarcoma, but otherwise there is no convincing evidence of superiority over cyclophosphamide. Gastrointestinal side effects and haemorrhagic cystitis seem to be more severe than after cyclophosphamide but this may be related to differences in dose rather than in biological activity. Disturbances of consciousness have been reported after ifosfamide. Treosulfan (Treosulfan Leo) is a derivative of busulphan used to treat ovarian cancer. Like busulphan it is myelo-suppressive and causes skin pigmentation. NEW DEVELOPMENTS WITH ALKYLATING AGENTS The oxazophosphorenes (cyclophosphamide and ifosfamide) cause haemorrhagic cystitis because an inactive metabolite,

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Structure-activity relationships and inhibitory effects of various purine derivatives on the in vitro growth of Plasmodium falciparum11Abbreviations: CDK, cyclin-dependent kinase; CDK1, cyclin-dependent kinase 1; and PfPK, Plasmodium falciparum protein kinase.

Cited by 52 publications

References 21 publications

Synthesis of 2-(aminomethyl)aziridines and their microwave-assisted ring opening to 1,2,3-triaminopropanes as novel antimalarial pharmacophores

Synthesis of 2-(aminomethyl)aziridines and their microwave-assisted ring opening to 1,2,3-triaminopropanes as novel antimalarial pharmacophores

The kinomes of apicomplexan parasites

The Use of Anticancer Drugs in Antiparasitic Chemotherapy

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