Antimalarial and antiproliferative evaluation of Bis-Steroidal tetraoxanes

Opsenica, Dejan; Angelovski, Goran; Pocsfalvi, Gabriella; Juranić, Zorica D.; Zizak, Zeljko; Kyle, Dennis E.; Milhous, Wilbur K.; Šolaja, Bogdan A.

doi:10.1016/s0968-0896(03)00224-4

Cited by 43 publications

(42 citation statements)

References 22 publications

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“…Furthermore we showed that steroidal tetraoxanes inhibit cancer cell proliferation at micromolar and submicromolar levels through an apoptotic mechanism [6,13,14]. This was determined by morphological observation of treated cells.…”

Section: Introductionmentioning

confidence: 87%

Mixed steroidal tetraoxanes induce apoptotic cell death in tumor cells

et al. 2008

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In this study we investigated the antiproliferative activity of six mixed steroidal tetraoxanes against various tumor cell lines, the toxicity against normal peripheral blood mononuclear cells (PBMC), and the mode of HeLa cell death induced by these compounds. Investigated tetraoxanes exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. Treatment of HeLa cells for 24 h with all tetraoxanes induced apoptosis, as confirmed by morphological analysis and by the appearance of a typical ladder pattern in the DNA fragmentation assay.

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Section: Introductionmentioning

confidence: 87%

Mixed steroidal tetraoxanes induce apoptotic cell death in tumor cells

et al. 2008

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“…A series of such cis and trans bis-steroidal tetraoxane compounds have now been synthesised and evaluated for both antimalarial and antiproliferative activities [75,76]. Only submicromolar concentrations are sufficient to kill P. falciparum cultures in vitro.…”

Section: Inhibitors From Plantsmentioning

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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“…[74,77] enzyme inhibitors signal transduction oxindole derivatives glycolysis 5-fluoroorotate, actinonin, gossypol derivatives [121] amino acid biosynthesis glyphosate heme-polymerization (hemedetoxification) [11,64,76,161] chloroquine, amodiaquine, halofantrine [66], lumefantrine [67] pyronaridine [78,79] tafenoquine [67,80] new quinolines [62,63,65,81,162,163] hemoglobin uptake from host cell quinine, mefloquine [11,161] artemisinin, dihydroartemisinin, artemether, arteether, artesunate ? [82,104] artemisinin analogs [82,96,97], (trioxanes [99,100], trioxolanes [101], trioxaquines [104], trioxalaquines tetraoxanes [102,103] …”

Section: Chemotherapies Of Toxoplasmosismentioning

confidence: 99%

“…Therefore, considerable efforts have been devoted to the design of the second-generation artemisinin derivatives with improved hydrophilicity, stability and bioavailability [67,82]. The simplification of the artemisinin core led to the development of several peroxides [96][97][98], trioxanes [99,100], trioxolanes [101], and tetraoxanes [102,103], some of which demonstrated remarkable antimalarial activity higher than that of artesunate, artemether, chloroquine and mefloquine. Promising drug hybrids or prodrugs as a covalent combination of a peroxidic moiety with an aminoquinoline entity (as in trioxaquines [104] 3 and trioxalaquines [82]) have also been reported.…”

Section: Artemisinin Derivativesmentioning

confidence: 99%

Quinolone-Based Drugs Against Toxoplasma gondii and Plasmodium spp

Anquetin

Greiner²,

Vierling³

2005

CDTID

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Owing to the rapid emergence of multi-resistant strains of Plasmodium spp. (the causative agents of malaria) and the limitations of drugs used against Toxoplasma gondii (an important opportunistic pathogen associated with AIDS and congenital birth defects), the discovery of new therapeutical targets and the development of new drugs are needed. The presence of the prokaryotic-like organelle in apicomplexan parasites (i.e. plastids), which comprise these major human pathogens, may represent a unique target for antibiotics against these protozoa. Quinolones which are known to be highly potent against bacteria were also found to specifically disrupt these parasites. They inhibit DNA replication by interacting with two essential bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. There are some clues that quinolones act on plastids with a similar mechanism of action. After a brief presentation of plasmodium and toxoplasma dedicated to their life cycle, the chemotherapies presently used in clinics to fight against these protozoa and the potential new targets and drugs, we will focus our attention on their plastid which is one of these promising new targets. Then, we will present the various drugs and generations of quinolones, the leading molecules, and their inhibitory effects against these parasites together with their pharmacological properties that have been established from in vitro and in vivo studies. We will also discuss their possible mode of action.

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Antimalarial and antiproliferative evaluation of Bis-Steroidal tetraoxanes

Cited by 43 publications

References 22 publications

Mixed steroidal tetraoxanes induce apoptotic cell death in tumor cells

Mixed steroidal tetraoxanes induce apoptotic cell death in tumor cells

The Use of Anticancer Drugs in Antiparasitic Chemotherapy

Quinolone-Based Drugs Against Toxoplasma gondii and Plasmodium spp

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