2699-11-8Relevant academic research and scientific papers
Synthesis and evaluation of the antimalarial, anticancer, and caspase 3 activities of tetraoxane dimers
Amewu, Richard K.,Chadwick, James,Hussain, Afthab,Panda, Somnath,Rinki, Rinki,Janneh, Omar,Ward, Stephen A.,Miguel, Candel,Burrell-Saward, Hollie,Vivas, Livia,O'Neill, Paul M.
, p. 7392 - 7397 (2013)
The synthesis of a range of mono spiro and dispiro 1,2,4,5-tetraoxane dimers is described. Selected molecules were examined in in vitro assays to determine their antimalarial and anticancer potential. Our studies reveal that several molecules possess potent nanomolar antimalarial and single digit micromolar antiproliferative IC50s versus colon (HT29-AK and leukemia (HL60) cell lines.
Synthesis and antileishmanial activity of 1,2,4,5-tetraoxanes against leishmania donovani
Cabral, Lília I.L.,Pomel, Sébastien,Cojean, Sandrine,Amado, Patrícia S.M.,Loiseau, Philippe M.,Cristiano, Maria L.S.
, (2020)
A chemically diverse range of novel tetraoxanes was synthesized and evaluated in vitro against intramacrophage amastigote forms of Leishmania donovani. All 15 tested tetraoxanes displayed activity, with IC50 values ranging from 2 to 45 μm. The most active tetraoxane, compound LC140, exhibited an IC50 value of 2.52 ± 0.65 μm on L. donovani intramacrophage amastigotes, with a selectivity index of 13.5. This compound reduced the liver parasite burden of L. donovani-infected mice by 37% after an intraperitoneal treatment at 10 mg/kg/day for five consecutive days, whereas miltefosine, an antileishmanial drug in use, reduced it by 66%. These results provide a relevant basis for the development of further tetraoxanes as effective, safe, and cheap drugs against leishmaniasis.
A new method for the synthesis of bishydroperoxides based on a reaction of ketals with hydrogen peroxide catalyzed by boron trifluoride complexes
Terent'ev, Alexander O.,Kutkin, Alexander V.,Platonov, Maxim M.,Ogibin, Yuri N.,Nikishin, Gennady I.
, p. 7359 - 7363 (2003)
A reaction of cycloalkanone, alkanone and alkyl aryl ketone ketals with H2O2 catalyzed by boron trifluoride etherate and boron trifluoride-methanol complexes was studied. A new versatile method for the synthesis of bishydroperoxides and their derivatives, viz. 1,1′ -dihydroperoxyperoxides and 1,2,4,5-tetraoxacyclohexanes, was developed based on this reaction.
Synthesis of Non-symmetrical Dispiro-1,2,4,5-Tetraoxanes and Dispiro-1,2,4-Trioxanes Catalyzed by Silica Sulfuric Acid
Amado, Patrícia S. M.,Coelho, Jaime A. S.,Cristiano, Maria L. S.,Frija, Luís M. T.,O'neill, Paul M.
, p. 10608 - 10620 (2021/07/31)
A novel protocol for the preparation of non-symmetrical 1,2,4,5-tetraoxanes and 1,2,4-trioxanes, promoted by the heterogeneous silica sulfuric acid (SSA) catalyst, is reported. Different ketones react under mild conditions with gem-dihydroperoxides or peroxysilyl alcohols/β-hydroperoxy alcohols to generate the corresponding endoperoxides in good yields. Our mechanistic proposal, assisted by molecular orbital calculations, at the ωB97XD/def2-TZVPP/PCM(DCM)//B3LYP/6-31G(d) level of theory, enhances the role of SSA in the cyclocondensation step. This novel procedure differs from previously reported methods by using readily available and inexpensive reagents, with recyclable properties, thereby establishing a valid alternative approach for the synthesis of new biologically active endoperoxides.
Synthesis, Antimalarial Activity Evaluation and Molecular Docking Studies of Some New Substituted Spiro-1,2,4,5-Tetraoxane Derivatives
Chetia, Dipak,Kumawat, Mukesh Kumar
, p. 814 - 820 (2021/11/26)
Eight new substituted spiro-1,2,4,5-tetraoxane derivatives were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were subsequently screened for in vitro antimalarial activity against chloroquine sensitive (3D7) and chloroquine resistant (RKL-9) strains of Plasmodium falciparum. These substituted spiro-1,2,4,5-tetraoxane derivatives were studied by molecular docking analysis in the active site of Falcipain-2 as a putative protein. Most of the synthesized compounds exhibited moderate to very good activity toward the parasite in comparison to the standard drug, chloroquine. Three compounds showed potent antimalarial activity against chloroquine sensitive strain of P. falciparum (3D7). One compound 5b (3-ethyl-3-methyl-1,2,4,5-tetraoxa-spiro[5.5]undecane) showed a very good activity against both chloroquine sensitive strain (3D7) with MIC = 1.95 ± 0.06 μg/mL and IC50 = 1.95 ± 0.06 μg/mL compared to chloroquine (MIC = 0.4 ± 0.10 μg/mL, IC50 = 0.04 ± 0.01 μg/mL) as well as chloroquine-resistant strain of P. falciparum (RKL-9) with MIC = 15.63 ± 0.70 μg/mL and IC50 = 3.90 ± 0.09 μg/mL compared to chloroquine (MIC = 25.00 ± 0.20 μg/mL, IC50 = 0.39 ± 0.02 μg/mL). The top scored compounds having low binding energy interact with the active site of Falcipain-2 in molecular docking studies.
Tetroxanes as New Agents against Leishmania amazonensis
Almeida, Raquel M.,Antolínez, Isabel V.,Baldaia, Almodvar,Barbosa, Luiz C. A.,Borgati, Tatiane F.,Ferreira, Sebasti?o R.,Fujiwara, Ricardo T.
, (2020/05/25)
Leishmaniasis is a neglected disease, caused by a parasite of Leishmania genus and widespread in the tropical and subtropical areas of the world. Currents drugs are limited due to their toxicity and parasite resistance. Therefore, the discovery of new treatment, more effective and less toxic, is urgent. In this study, we report the synthesis of six gem-dihydroperoxides (2a–2f), with yields ranging from 10 % to 90 %, utilizing a new methodology. The dihydroperoxides were converted into ten tetroxanes (3a–3j), among which six (3b, 3c, 3d, 3g, 3h and 3j) showed activity against intracellular amastigotes of Leishmania amazonensis. The cytotoxicity of all compounds was also evaluated against canine macrophages (DH82), human hepatoma (HepG2) and monkey renal cells (BGM). Most compounds were more active and less toxic than potassium antimonyl tartrate trihydrate, used as positive control. Amongst all tetroxanes, 3b (IC50=0.64 μm) was the most active, being more selective than positive control in relation to DH82, HepG2 and BGM cells. In summary, the results revealed a hit compound for the development of new drugs to treat leishmaniasis.
Perhydrolysis in Ethereal H2O2 Mediated by MoO2(acac)2: Distinct Chemoselectivity between Ketones, Ketals, and Epoxides
An, Xiaosheng,Zha, Qinghong,Wu, Yikang
supporting information, p. 1542 - 1546 (2019/02/26)
Ketones, ketals, and epoxides were converted into corresponding hydroperoxides in high yields by reaction with ethereal H2O2 in the presence of a catalytic amount of MoO2(acac)2 with distinct (to date unattainable) chemoselectivity.
Di(hydroperoxy)alkane Adducts of Phosphine Oxides: Safe, Solid, Stoichiometric, and Soluble Oxidizing Agents
Ahn, Shin Hye,Bhuvanesh, Nattamai,Blümel, Janet
, p. 16998 - 17009 (2017/10/12)
The di(hydroperoxy)alkane adducts of phosphine oxides 1–9, Ph3PO?(HOO)2CMe2, Cy3PO?(HOO)2CMe2, Ph3PO? (HOO)2CMeEt, Cy3PO?(HOO)2CMeEt, Cy3PO?(HOO)2CEt2, Cy3PO? (HOO)2C(CH2)5, Cy3PO?(HOO)2CMePh, (Ph2P(O)CH2CH2P(O)Ph2)? ((HOO)2CEt2)2, and Ph2P(O)CH2P(O)Ph2?(HOO)2CMe2, respectively, are synthesized and fully characterized by 1H, 13C, and 31P NMR, and IR spectroscopies. Single crystal X-ray structures are reported for 3–9. Different one-pot synthetic pathways, starting from R3P, R3PO, R3PO?H2O, and R3PO?H2O2 are explored and discussed and a mechanism for the formation of the di(hydroperoxy)alkane adducts of phosphine oxides is suggested. The longevity of the adducts is tested by monitoring the oxidation of Ph3P with quantitative NMR. The solubilities of the adducts in organic solvents are presented, and their applicability as stoichiometric oxidizing agents for the selective oxidation of sulfides to sulfoxides is reported.
Heteropoly acid/NaY zeolite as a reusable solid catalyst for highly efficient synthesis of gem-dihydroperoxides and 1,2,4,5-Tetraoxanes
Khosravi, Kaveh,Zendehdel, Mojgan,Naserifar, Shirin,Tavakoli, Fatemeh,Khalaji, Kobra,Asgari, Atefeh
, p. 744 - 749 (2016/12/30)
Gem-Dihydroperoxides and 1,2,4,5-Tetraoxanes were synthesised from aldehydes and ketones catalysed by heteropoly acid/NaY zeolite (HPA/NaY) as a new, effective and reusable solid catalyst using 30% aqueous hydrogen peroxide at room temperature. The reactions proceeded with high rates and excellent yields.
Synthesis, antimalarial activity evaluation and docking studies of some novel tetraoxaquines
Kumawat, Mukesh Kumar,Parida, Pratap,Chetia, Dipak
, p. 1993 - 2004 (2016/10/03)
Tetraoxaquines, molecular hybrids of 1,2,4,5-tetraoxane and 4-aminoquinoline, were designed via molecular docking analysis against Falcipain-2. Among the studied compounds, 11 top scoring analogues showing low binding energy were further selected for synthesis and evaluated for their in vitro antimalarial activity. In inhibitory assay, five compounds showed significant activity against chloroquine-resistant strain of P. falciparum-RKL-9 with IC50 values of 3.906, 3.942, 4.272, 3.906, 4.814 μg/ml.
