Access to new highly potent antileukemia, antiviral and antimalarial agents via hybridization of natural products (homo)egonol, thymoquinone and artemisinin
Hybridization of natural products has high potential to further improve their activities and may produce synergistic effects between linked pharmacophores. Here we report synthesis of nine new hybrids of natural products egonol, homoegonol, thymoquinone and artemisinin and evaluation of their activities against P. falciparum 3D7 parasites, human cytomegalovirus, sensitive and multidrug-resistant human leukemia cells. Most of the new hybrids exceed their parent compounds in antimalarial, antiviral and antileukemia activities and in some cases show higher in vitro efficacy than clinically used reference drugs chloroquine, ganciclovir and doxorubicin. Combined, our findings stress the high pot…
New efficient artemisinin derived agents against human leukemia cells, human cytomegalovirus and Plasmodium falciparum: 2nd generation 1,2,4-trioxane-ferrocene hybrids
Abstract In our ongoing search for highly active hybrid molecules exceeding their parent compounds in anticancer, antimalaria as well as antiviral activity and being an alternative to the standard drugs, we present the synthesis and biological investigations of 2nd generation 1,2,4-trioxane-ferrocene hybrids. In vitro tests against the CCRF-CEM leukemia cell line revealed di-1,2,4-trioxane-ferrocene hybrid 7 as the most active compound (IC50 of 0.01 μM). Regarding the activity against the multidrug resistant subline CEM/ADR5000, 1,2,4-trioxane-ferrocene hybrid 5 showed a remarkable activity (IC50 of 0.53 μM). Contrary to the antimalaria activity of hybrids 4–8 against Plasmodium falciparum …
Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities
New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC50 of 2.6 nM) possess superior antimalarial activity compared with its parent compound artesunic acid(3) (IC50 of 9.0 nM). Dimer5 and trimers6 and 7 disp…
Empirical calibration of the clumped isotope paleothermometer using calcites of various origins
We present the first universal calibration of the clumped isotope thermometer for calcites of various mineralizing types. These are an eggshell of an ostrich, a tropical bivalve, a brachiopod shell, cold seep carbonate, and three foraminifera samples that grew between 9 and 38 C. CaCO3 was digested at 90 C using a common acid bath. Considering a difference in phosphoric acid fractionation factors between reaction at 25 and 90 C of 0.069& (Guo et al., 2009), the function between growth temperature T and the excess of 13 C– 18 O bonds in the evolved CO2 is expressed by a linear regression between 1/T 2 and absolute D47 (R 2 = 0.9915):
Synthesis of Thymoquinone–Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents
[Image: see text] A series of hybrid compounds based on the natural products artemisinin and thymoquinone was synthesized and investigated for their biological activity against the malaria parasite Plasmodium falciparum 3D7 strain, human cytomegalovirus (HCMV), and two leukemia cell lines (drug-sensitive CCRF-CEM and multidrug-resistant subline CEM/ADR5000). An unprecedented one-pot method of selective formation of C-10α-acetate 14 starting from a 1:1 mixture of C-10α- to C-10β-dihydroartemisinin was developed. The key step of this facile method is a mild decarboxylative activation of malonic acid mediated by DCC/DMAP. Ether-linked thymoquinone–artemisinin hybrids 6a/b stood out as the most…
CCDC 1816140: Experimental Crystal Structure Determination
Related Article: Aysun Çapcı Karagöz, Christoph Reiter, Ean-Jeong Seo, Lisa Gruber, Friedrich Hahn, Maria Leidenberger, Volker Klein, Frank Hampel, Oliver Friedrich, Manfred Marschall, Barbara Kappes, Thomas Efferth, Svetlana B. Tsogoeva|2018|Bioorg.Med.Chem.|26|3610|doi:10.1016/j.bmc.2018.05.041
CCDC 1816139: Experimental Crystal Structure Determination
Related Article: Aysun Çapcı Karagöz, Christoph Reiter, Ean-Jeong Seo, Lisa Gruber, Friedrich Hahn, Maria Leidenberger, Volker Klein, Frank Hampel, Oliver Friedrich, Manfred Marschall, Barbara Kappes, Thomas Efferth, Svetlana B. Tsogoeva|2018|Bioorg.Med.Chem.|26|3610|doi:10.1016/j.bmc.2018.05.041
CCDC 994084: Experimental Crystal Structure Determination
Related Article: Christoph Reiter, Tony Fröhlich, Maen Zeino, Manfred Marschall, Hanife Bahsi, Maria Leidenberger, Oliver Friedrich, Barbara Kappes, Frank Hampel, Thomas Efferth, Svetlana B. Tsogoeva|2015|Eur.J.Med.Chem.|97|164|doi:10.1016/j.ejmech.2015.04.053
CCDC 994085: Experimental Crystal Structure Determination
Related Article: Christoph Reiter, Tony Fröhlich, Maen Zeino, Manfred Marschall, Hanife Bahsi, Maria Leidenberger, Oliver Friedrich, Barbara Kappes, Frank Hampel, Thomas Efferth, Svetlana B. Tsogoeva|2015|Eur.J.Med.Chem.|97|164|doi:10.1016/j.ejmech.2015.04.053