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《Journal of Coordination Chemistry》2012,65(21):3367-3374
We present the synthesis, characterization and in vitro antiplasmodial and antitrypanosomal studies of iron(III) complexes of amodiaquine, trimethoprim and pyrimethamine. The complexes have been characterized by elemental analyses, electronic and IR spectroscopy and room temperature magnetic susceptibility measurements. The spectra are consistent with octahedral geometry around the metal ions. The complexes were tested for in vitro activity against cultures of Plasmodium falciparum, Tripanosoma brucei rhodosiense, L. donovani and Tripanosoma cruzi. One of the complexes showed enhanced activity of about 8.4 times more than chloroquine against the resistant strain of Plasmodium falciparum. 相似文献
3.
Modeling studies were performed on known inhibitors of the quadruple mutant Plasmodium falciparum dihydrofolate reductase (DHFR). GOLD was used to dock 32 pyrimethamine derivatives into the active site of DHFR obtained
from the x-ray crystal structure 1J3K.pdb. Several scoring functions were evaluated and the Molegro Protein-Ligand Interaction
Score was determined to have one of the best correlation to experimental pK
i
. In conjunction with Protein-Ligand Interaction scores, predicted binding modes and key protein-ligand interactions were
evaluated and analyzed in order to develop criteria for selecting compounds having a greater chance of activity versus resistant
strains of Plasmodium falciparum. This methodology will be used in future studies for selection of compounds for focused screening libraries. 相似文献
4.
《Magnetic resonance in chemistry : MRC》2002,40(7):477-479
We report the 1H NMR and 13C NMR chemical shifts and J(H,H), J(H,F) and J(C,F) coupling constants of 13 2,4‐diamino‐10‐methylpyrimido[4,5‐b]‐5‐quinolone derivatives, some of them with moderate activity against Plasmodium falciparum in vitro. They were characterized and assigned on the basis of 1H, 13C and 13C–1H (short‐ and long‐range) correlated spectra. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
5.
Total Synthesis and Biological Investigation of (−)‐Artemisinin: The Antimalarial Activity of Artemisinin Is not Stereospecific
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Johannes Krieger Toni Smeilus Dr. Marcel Kaiser Dr. Ean‐Jeong Seo Prof. Thomas Efferth Prof. Athanassios Giannis 《Angewandte Chemie (International ed. in English)》2018,57(27):8293-8296
Here, we describe an efficient and diversity‐oriented entry to both (?)‐artemisinin ( 1 ) and its natural antipode (+)‐artemisinin, starting from commercially and readily available S‐(+)‐ and R‐(?)‐citronellene, respectively. Subsequently, we answered the still open question regarding the specificity of artemisinins action. By using a drug‐sensitive Plasmodium falciparum NF54 strain, we showed that the antimalarial activity of artemisinin is not stereospecific. Our straightforward and biomimetic approach to this natural endoperoxide enables the synthesis of artemisinin derivatives that are not accessible through applying current methods and may help to address the problem of emerging resistance of Plasmodium falciparum towards artemisinin. 相似文献
6.
Boonyanoot Chaiyosang Kwanjai Kanokmedhakul Jaursup Boonmak Sujittra Youngme Veerapol Kukongviriyapan Kasem Soytong 《Natural product research》2016,30(9):1017-1024
A new rare lumazine peptide, penilumamide E (1), together with 13 known compounds (2–14) were isolated from the fungus Aspergillus terreus. Their structures were identified by spectroscopic techniques. The relative configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 10 exhibited antimalarial activity against Plasmodium falciparum with IC50 values of 2.83 μg/mL. Compounds 4 and 6 showed weak cytotoxicity against cholangiocarcinoma (CCA) cell lines. In addition, 4 and 11 exhibited weak cytotoxicity against human hepatoma cell line. 相似文献
7.
Judith Johnson Edward F. Elslager Leslie M. Werbel 《Journal of heterocyclic chemistry》1979,16(6):1101-1104
Amination of 5-chloro-6-nitro-2,4-quinazolinediamine ( 2 ) afforded 6-nitro-2,4,5-quinazolinetriamine ( 3 ) which was hydrogenated catalytically to produce 2,4,5,6-quinazolinetetraamine ( 5 ). Condensation of 5 with the requisite diketones afforded 8,9,10,11-tetrahydropyrimido[5,4-a]-phenazine-1,3-diamine ( 6 ), several pyrazino[2,3-f]quinazoline-8,10-diamines ( 7–10,13 ) as well as two pyrimido[4,5-f]phenazinediamines ( 11,12 ). Amination of 2 in the presence of formamide at 120° led to the formation of 9-nitro-1H-pyrimido[4,5,6-de]quinazolin-5-amine ( 4 ). None of these compounds showed suppressive activity when tested parenterally against lethal Plasmodium berghei infections in mice. When tested against various bacteria in vitro, 7 and 10 exhibited activity against Streptococcus faecalis at a concentration below 2.5 μg./ml. 相似文献
8.
Summary. New derivatives of 4-aminobicyclo[2.2.2]octanones and -ols were prepared. Their structures were established by means of NMR experiments. All new compounds were tested for their activities against Plasmodium falciparum and Trypanosoma b. rhodesiense. One of the bicyclooctanols showed promising antitrypanosomal activity. 相似文献
9.
Leslie M. Werbel Edward F. Elslager Linda S. Newton 《Journal of heterocyclic chemistry》1987,24(2):345-349
A series of 2,4-diamino-6-[(N-alkylanilino)methyl]quinazolines were prepared by bromination of 2,4-dibenz-amido-6-methylquinazoline followed by treatment with secondary arylamines and deblocking with base. A variety of analogs demonstrated substantial activity against Plasmodium berghei infections in mice. 相似文献
10.
Daniel Reker Dr. Michael Seet Max Pillong Dr. Christian P. Koch Dr. Petra Schneider Dr. Matthias C. Witschel Dr. Matthias Rottmann Céline Freymond Prof. Dr. Reto Brun Dr. Bernd Schweizer Dr. Boris Illarionov Prof. Dr. Adelbert Bacher Prof. Dr. Markus Fischer Prof.Dr. François Diederich Prof. Dr. Gisbert Schneider 《Angewandte Chemie (International ed. in English)》2014,53(27):7079-7084
The discovery of pyrrolopyrazines as potent antimalarial agents is presented, with the most effective compounds exhibiting EC50 values in the low nanomolar range against asexual blood stages of Plasmodium falciparum in human red blood cells, and Plasmodium berghei liver schizonts, with negligible HepG2 cytotoxicity. Their potential mode of action is uncovered by predicting macromolecular targets through avant‐garde computer modeling. The consensus prediction method suggested a functional resemblance between ligand binding sites in non‐homologous target proteins, linking the observed parasite elimination to IspD, an enzyme from the non‐mevalonate pathway of isoprenoid biosynthesis, and multi‐kinase inhibition. Further computational analysis suggested essential P. falciparum kinases as likely targets of our lead compound. The results obtained validate our methodology for ligand‐ and structure‐based target prediction, expand the bioinformatics toolbox for proteome mining, and provide unique access to deciphering polypharmacological effects of bioactive chemical agents. 相似文献
11.
Sébastien Charneau Mariana Laundry de Mesquita Izabela Marques Dourado Bastos Jaime Martins Santana José Elias de Paula Philippe Grellier 《Natural product research》2016,30(11):1320-1326
The threatened Brazilian Cerrado biome is an important biodiversity hotspot but still few explored that constitutes a potential reservoir of molecules to treat infectious diseases. We selected eight Cerrado plant species for screening against the erythrocytic stages of Plasmodium falciparum, human intracellular stages of Trypanosoma cruzi and bloodstream forms of T. brucei gambiense, and for their cytotoxicity upon the rat L6-myoblast cell line. Bioassays were performed with 37 hexane, ethyl acetate and ethanol extracts prepared from different plant organs. Activities against parasites were observed for 24 extracts: 9 with anti-P. falciparum, 4 with anti-T. cruzi and 11 with anti-T. brucei gambiense activities. High anti-protozoal activity (IC50 values < 10 μg/mL) without obvious cytotoxicity to L6 cells was observed for eight extracts from plants: Connarus suberosus, Blepharocalyx salicifolius, Psidium laruotteanum and Myrsine guianensis. Overall, studies of plant extracts will contribute to increase the biodiversity knowledge essential for Cerrado conservation and sustainable development. 相似文献
12.
Metal complexes of the antimalarials trimethoprim (TMP), chloroquine (CQ), and pyrimethamine (pyrm) formulated as [Mn(TMP)Cl2(CH3OH)], [Co(TMP)2Cl2(CH3OH)], [Pt(CQ)2Cl2] and [Cu(pyrm)2(CH3COO)2] have been synthesized and characterized by elemental analysis, magnetic susceptibility measurements, IR and UV-Vis spectroscopy.
The IR and electronic spectra are consistent with the proposed geometry for the complexes. The Mn(II) and Pt(II) complexes
are four coordinate while the Cu(II) and Co(II) have octahedral geometry. The complexes were tested for in vitro activity
against cultures of Trypanosoma
cruzi, L. donovani, T. b. rhodesiense and the resistant strains of Plasmodium falciparum to determine their antiprotozoal activities and for their cytotoxicity with L-6 cells. The Pt(II) complex of chloroquine
showed enhanced activity against the resistant strain of Plasmodium falciparum. 相似文献
13.
Werner Seebacher Reto Brun Robert Saf Dietmar Kr?pfl Robert Weis 《Monatshefte für Chemie / Chemical Monthly》2004,31(6):313-322
New derivatives of 4-aminobicyclo[2.2.2]octanones and -ols were prepared. Their structures were established by means of NMR experiments. All new compounds were tested for their activities against Plasmodium falciparum and Trypanosoma b. rhodesiense. One of the bicyclooctanols showed promising antitrypanosomal activity. 相似文献
14.
Patricia Mollinedo José L. Vila Hugo Arando Michel Sauvain Eric Deharo 《Natural product research》2016,30(22):2594-2597
The search for anti-infective activity in the antipyretic plant Senecio smithioides was conducted. Petroleum ether (PE), dichloromethane (CH2Cl2), ethyl acetate (EtOAc) and hydroethanolic (96% EtOH) extracts, and compounds 9-oxoeuryopsin (1), epoxydecompostin (2) and senecionine (3) were obtained from the aerial parts. All extracts and 1 were tested against chloroquine-resistant strain of Plasmodium falciparum (ref. chloroquine), Trypanosoma cruzi (ref. nifurtimox), Leishmania braziliensis, Leishmania amazonensis and Leishmania donovani (ref. pentamidine), Staphylococcus aureus and Escherichia coli (ref. gentamicin) and, Neurospora crassa and Candida albicans (ref. ketoconazole). The PE extract exhibited the strongest in vitro activity against Plasmodium falciparum IC50 < 1.0 μg/mL. 1 was established as a potent antiplasmodial compound with an IC50 = 1.2 μg/mL, 5.2 μM. Other antiparasitic activities were recorded for all extracts and 1. Antibacterial and antifungal activity was negligible. 相似文献
15.
Edward F. Elslager S. C. Perricone Donald F. Worth 《Journal of heterocyclic chemistry》1970,7(3):543-553
Various 2-alkoxy 7-chloro-10-[[[(dialkylamino)alkyl]amino]]benzo[b][1,5]naphthyridines (XI) and N-oxides (XV, XVII, XVIII, XXII), 4-[(2-alkoxy-7-chlorobenzo[b][1,5]naphthyridin-10-yl)-amino]-α-(diethylamino)-o-cresol derivatives (XII-XIV, XXI) and N-oxides (XIX, XX, XXV), 2-butoxy-8-[[[(dialkylamino)alkyl]amino]]-1,5-naphthyridines (XXVIa and b), and 2-butoxy-8–[[3-[(diethylamino)methyl]-p-anisidino]]-1,5-naphthyridine (XXVII) were synthesized for antifilarial and antimalarial evaluation. The compounds were obtained in 13–91% yield by the condensation of 2-alkoxy-7,10-dichlorobenzo[b][1,5]naphthyridines, 2-alkoxy-7,10-dichlorobenzo[b][1,5]naphthyridine 5-oxides, and 2-butoxy-8-chloro-1,5-naphthyridine with the appropriate diamine in phenol, or by perbenzoic acid oxidation of the parent 10-amino-7-chlorobenzo-[b][1,5] naphthyridines in chloroform. Among them, eight compounds killed adult Litomosoides carinii in gerbils when administered in daily gavage doses of 25–400 mg./kg. for 5 days. Azacrine 5-oxide (XVII), the most active compound, was equipotent with amodiaquine (1a), azacrine (IX), and quinacrine 10-oxide (VI). Twelve substances were active orally against Plasmodium berghei in mice at doses ranging from 3.8–155 mg./kg./day for 6 days. 7-Chloro-10-[[-3-[(diethylamino)-methyl]-p-anisidino]]-2-methoxybenzo[b][1,5]naphthyridine 5-oxide dihydrochloride (XX) was approximately 12 times as potent as quinine against P. berghei, but was highly cross-resistant with chloroquine (IV). Structure-activity relationships are discussed. 相似文献
16.
Charles W. Jefford Javier A. Velarde Grald Bernardinelli Dorothy H. Bray David C. Warhurst Wilbur K. Milhous 《Helvetica chimica acta》1993,76(8):2775-2788
Two sets of tricyclic 1,2,4-trioxanes containing the ABC ( 10 , 11 ) and ACD ring portions ( 21 , 22 , 32 , 33 , 37 , and 38 ) of artemisinin ( 1 ) were synthesized by successive photo-oxygenation of appropriate enol-ether precursors to 1,2-dioxanes and inter- and intramolecular reaction with a carbonyl compound or oxo-substituted side-chain. The structures of 10 , 21 , and 22 were determined by X-ray analysis. The anti-malarial activity of all trioxanes, except 37 and 38 , was evaluated in vitro against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum parasites. Trioxanes 11 and 21 were as active as artemisinin ( 1 ). It was found that neither the lactone function nor rings B and D of 1 were essential for activity. A possible pharmacophore for artemisinin-like activity, which embodies a spirocyclopentane group attached to C(3) of 1,2,4-trioxane, was proposed. 相似文献
17.
Watchara Sangsopha Florian T. Schevenels Kwanjai Kanokmedhakul Somdej Kanokmedhakul 《Natural product research》2020,34(4):482-488
AbstractTwo new ceanothane triterpenes, 3,7-O,O-dibenzoyl ceanothic acid methylester (1) and 3-O-acetyl-7-O-benzoyl ceanothic acid methylester (2), along with nine known compounds (3–11), were isolated from the roots of Colubrina asiatica. The isolated compounds were identified by spectroscopic evidence. Compounds 1 and 2 showed antimalarial activity against Plasmodium falciparum with IC50 values of 4.67 and 3.07?µg/mL, respectively. Compound 2 also showed antimycobacterial activity against Mycobacterium tuberculosis (MIC 6.25?µg/mL). In addition, compounds 1, 2, 10 and 11 showed cytotoxicity against three cancer cell lines (KB, NCI-H187 and MCF-7) with IC50 values ranging from 8.32 to 46.72?µg/mL. 相似文献
18.
Watchara Sangsopha Kwanjai Kanokmedhakul Somdej Kanokmedhakul 《Natural product research》2018,32(10):1176-1179
Sixteen compounds were isolated from a Thai medicinal plant, Colubrina asiatica. The isolated compounds were elucidated on the basis of spectroscopic methods (IR, 1D and 2D NMR) as six triterpene acids (1–6), five steroids (7–11), one benzoic acid derivative (12), two peptides (13 and 14), one sesquiterpenoid (15) and one jujubogenin (16). Compounds 3 and 10 showed antimalarial activity against Plasmodium falciparum. Compound 5 showed antimycobacterial activity. Moreover, compounds 3, 5, 6, 10 and 14 exhibited weak cytotoxicity against cancer cell lines. Compounds 1–15 have been isolated for the first time from this plant. 相似文献
19.
We isolated four steroidal bitter principles from the rhizome of Tacca plantaginea Hance. The structures of taccalonolides A (1) and B (2) were elucidated by spectral and chemical methods, as a new type of pentacyclic steroidal γ-lactone. Taccalonolide A shows cytotoxic activity against P-388 leukemia in cell culture and antimalarial activity to Plasmodium berghai. 相似文献
20.
Werner Seebacher Reto Brun Robert Saf Robert Weis 《Monatshefte für Chemie / Chemical Monthly》2003,17(9):1411-1420
4-Aminobicyclo[2.2.2]octanones were converted to their N-oxides and to 4-aminobicyclo[2.2.2]octanes. Furthermore, the 6,7-bis-(4-methoxyphenyl) analogues were synthesized. All products were screened for their activities against Trypanosoma b. rhodesiense and Plasmodium falciparum. The pharmacological results were compared with those of formerly tested bicyclo[2.2.2]octanones and bicyclo[2.2.2]octanols. Structure-activity relationships are discussed. 相似文献