Trioxane dimers have potent antimalarial, antiproliferative and antitumor activities in vitro

Posner, Gary H.; Ploypradith, Poonsakdi; Hapangama, Whitney; Wang, Dasong; Cumming, Jared N.; Dolan, Patrick; Kensler, Thomas W.; Klinedinst, Donna; Shapiro, Theresa A.; Zheng, Qun Yi; Murray, Christopher K.; Pilkington, Lynn G.; Jayasinghe, Lalith; Bray, Jeff; Daughenbaugh, Randy

doi:10.1016/s0968-0896(97)00079-5

Cited by 52 publications

(49 citation statements)

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“…S -Oxidation of the arylthiotrioxanes 610 affords the corresponding arylsulfonyl trioxanes 611, which exhibit potent antimalarial activity 520,530 . Hydroxyl functions in substituents at positions 4 and 9 of tricyclic trioxanes 607 were utilized for tethering with bis(electrophiles), yielding antimalarial, antiproliferative and antitumor active trioxane dimers 471 . The cyclic enol ether 612, bearing highly sensitive styryl substituent at the ketone tether, was used for the synthesis of tetracyclic trioxane 613 (Scheme 173) 524 .…”

Section: B Peroxyacetalization Of Carbonyl Functions With Strained Ementioning

confidence: 99%

Synthesis of Cyclic Peroxides

Korshin

Bachi

2009

Patai's Chemistry of Functional Groups

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Section: B Peroxyacetalization Of Carbonyl Functions With Strained Ementioning

confidence: 99%

Synthesis of Cyclic Peroxides

Korshin

Bachi

2009

Patai's Chemistry of Functional Groups

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“…5). The first generation C-10 acetal derivatives, even though very simple in their synthesis had the disadvantage of being easily hydrolysed in water [64,65]. To overcome this problem of instability, Posner and coworkers have subsequently succeeded in converting C-10 acetate directly into C-10 non-acetal trioxane dimers [66].…”

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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“…Further investigation of the mechanism of this transformation by treatment of the hydroperoxide 151, derived from methyl ester of artemisinic acid, with the Cu(II) catalyst in the presence of oxygen suggests that a thermally labile, ring-cleaved enol 152 is a key intermediate (Scheme 53) [107]. The diastereoisomeric alcohols 154, derived from dihydroartemisinic acid 153, are transformed into the ring D-contracted artemisinin analogues 155 on reaction in turn with singlet oxygen followed by Cu(II)(OTf) 2 Two series of dimers 149 and 150, derived from either tricylic trioxanes or dihydroartemisin, have been prepared by conventional chemistry and found to exhibit antipoliferative and antitumour as well as antimalarial activity [106]. Artemisitene 161, which is also extracted in significant quantities from A. annua, readily undergoes TiCl 4 -catalysed coupling with allyltrimethylsilane, or trimethylsilyl cyanide or trimethylsilyl enol ethers under Mukaiyama conditions affording some new artemisinin derivatives 162 (usually as a mixture of isomers) in which the C-9 side chain is modified (Scheme 57) [111].…”

Section: Scheme 44mentioning

confidence: 99%

Recent Advances in the Chemistry of Cyclic Peroxides

McCullough¹,

Nojima

2001

COC

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The well-known antimalarial properties of naturally occurring cyclic peroxides artemisinin (qinghaosu), yingzhaosu A and yingzhaosu C have stimulated the development of new strategies for the synthesis of cyclic peroxides with diverse structures, and the investigation of the chemical transformations and properties of such compounds. In this review, recent progress in the chemistry of mono-and polycyclic organic peroxides with ring sizes of five or greater is highlighted and discussed.

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Trioxane dimers have potent antimalarial, antiproliferative and antitumor activities in vitro

Cited by 52 publications

References 20 publications

Synthesis of Cyclic Peroxides

Synthesis of Cyclic Peroxides

The Use of Anticancer Drugs in Antiparasitic Chemotherapy

Recent Advances in the Chemistry of Cyclic Peroxides

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