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Jurnal Natur Indonesia 15(1), Februari 2013: 57–62 Synthesis and antimalarial activity 57 Synthesis and Antimalarial Activity
of 2-Phenyl-1,10-Phenanthroline Derivative Compounds
Ruslin Hadanu1*), Mustofa2), and Nazudin1)
1)Department of Chemistry, Faculty of Teachership and Educational Science, Pattimura University, Poka, Ambon 97233 2)Department of Pharmacology and Toxicology, Faculty of Medicine, Gadjah Mada University, Sekip Utara, Yogyakarta Received 13-05-2011 Approved 29-03-2013 To develop new potential antimalarial drugs of 2-phenyl-1,10-phenanthroline 5 derivatives from 8-aminoquinoline as starting
material were synthesized in good yields. The synthesis of 2-phenyl-1,10-phenanthroline 5 derivatives compounds
with 8-aminoquinoline 4 as starting material through three steps has been carried out. The first step of reactions is aldol
condensation of benzaldehyde 1 with acetaldehyde 2. The result of reactions is cinnamaldehyde 3 (92.14%) in the form of
yellow solid. The second step of reactions was synthesized of 2-phenyl-1,10-phenanthroline 5 (brown solid, 54.63%)
through cyclization of 8-aminoquinoline 4 with cinnamaldehyde 3 compound. The third step of reactions is methylation and
ethylation of 2-phenyl-1,10-phenanthroline using dimethyl sulphate (DMS) and diethyl sulphate (DES) reagents that it was
refluxed for 17 and 19 h, respectively. The results of reactions are (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6
and (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 in yield from 90.62% and 89.70%, respectively. The results of
testing in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum FCR3 strain to 2-phenyl-1,10-
phenanthroline 5 derivatives obtained that (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 compound has higher
antimalarial activity (IC :0.13 ± 0.02 µM) than antimalarial activity of (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate
6 compound (IC :0.25 ± 0.01 µM) and 2-phenyl-1,10-phenanthroline 5 compound (IC :2.45 ± 0.09 µM). While, the results
of testing in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum D10 strain to 2-phenyl-1,10-
phenanthroline 5 derivatives obtained that (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6 compound has higher
antimalarial activity (IC :0.10± 0.04 µM) than antimalarial activity of (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate
7 (IC :0.18 ± 0.01 µM) and 2-phenyl-1,10-phenanthroline 5 compound (IC :0.55 ± 0.07 µM).
Keywords: 2-phenyl-1,10-phenanthroline derivatives, antimalarial activity, plasmodium, synthesis
Untuk mengembangkan obat baru antimalaria yang potensial dari senyawa turunan 2-fenil-1,10-fenantrolina 5 telah disintesis
dari 8-aminokuinolina sebagai bahan dasar. Sintesis senyawa turunan 2-fenil-1,10-fenantrolina 5 dari 8-aminokuinolina 4
telah dilakukan melalui tiga tahap reaksi. Langkah pertama adalah reaksi aldol kondensasi benzaldehida 1 dengan asetaldehida
2 menghasilkan senyawa sinnamaldehida 3 (92,14%) dalam bentuk padatan kuning. Langkah kedua adalah sintesis senyawa
2-fenil-1,10-fenantrolina 5 (padatan coklat, 54,63%) melalui siklisasi 8-aminokuinolina 4 dengan senyawa sinnamaldehida 3.
Langkah ketiga adalah reaksi metilasi dan etilasi terhadap senyawa 2-fenil-1,10-fenantrolina 5 menggunakan reagen dimetil
sulfat (DMS) dan dietil sulfat (DES) yang direfluks masing-masing selama 17 dan 19 jam. Hasil reaksi alkilasi tersebut adalah
(1)-N-metil-9-fenil-1,10-phenanthrolinium sulfat 6 dan (1)-N-etil-9-fenil-1,10-phenanthrolinium sulfat 7 dengan rendemen
berturut-turut sebesar 90,62% dan 89,70%. Hasil pengujian aktivitas antiplasmodial in vitro pada chloroquine-resistant
Plasmodium falciparum strain
FCR3 terhadap turunan 2-fenil-1,10-fenantrolin 5 diperoleh bahwa senyawa (1)-N-etil-9-
fenil-1,10-phenanthrolinium sulfat 7 memiliki aktivitas antimalaria yang lebih tinggi (IC : 0,13 ± 0,02 µM) dibandingkan
dengan aktivitas antimalaria dari senyawa (1)-N-metil-9-fenil-1,10-phenanthrolinium sulfat 6 (IC : 0,25 ± 0,01 µM) dan
senyawa 2-fenil- 1,10-fenantrolina 5 (IC : 2,45 ± 0,09 µM). Sementara, hasil pengujian aktivitas antiplasmodial in vitro pada
chloroquine-sensitive P. falciparum strain D10 terhadap senyawa 2-fenil-1,10-fenantrolina 5 diperoleh bahwa senyawa (1)-
N-metil-9-fenil-1,10-fenantrolina sulfat 6 memiliki aktivitas antimalaria yang lebih tinggi (IC : 0,10 ± 0,04 µM) dibandingkan
58 Jurnal Natur Indonesia 15(1): 57–62 Hadanu, et al. dengan aktivitas antimalaria dari senyawa (1)-N-etil-9-fenil-1,10-phenanthrolinium sulfat 7 (IC : 0,18 ± 0,01 M) dan senyawa
2-fenil-1,10-fenantrolina 5 (IC : 0,55 ± 0,07 pM).
Kata Kunci: aktivitas antimalaria, plasmodium, sintesis, turunan 2-fenil-1,10-fenantrolina
The halofantrine as new anti malaria has good Malaria is the most important parasitic disease in the therapeutic effects (Basco et al. 1994). Halofantrine as more world. Its etiological agents are protozoa of the genus active against strains of P. falciparum that are resistant to Plasmodium. Plasmodium falciparum is the most virulent chloroquine, pyrimethamine, and quine (Rang et al. 2003).
among the four species infecting humans and is responsible However, halofantrine is known to have some unwanted for most of mortality. In 2008, among 3.3 billion people at side effects, such as abdominal pain, nausea, vomiting, risk, there were 243 million malaria cases, causing an diarrhea, orthostatic, hypertension, prolongation of QTc estimated 863,000 deaths, mostly of children under five years.
intervals, pruritus, rash, and hepatotoxic (Karbwang et al. From 109 countries endemic for malaria, 45 were within the 1991; Bassi et al. 2006). The 1,10-phenanthroline derivatives World Health Organization (WHO 2009) Especially in African are similar to halofantrine as antimalarial drug which its added Region (Fernández et al. 2011; Fidock et al. 2004; Olumese at heterocyclic with two nitrogen atoms. (In 2000, Yapi 2005; Kayembe et al. 2010). Malaria remains one of the most reported) that the 1,10-phenanthroline ring system appeared important diseases of the developing world, killing 1–3 as new class of potential antimalarial compound (Yapi et al. million people and causing disease in 300–500 million people annually (Fidock et al. 2004; Olumese 2005, Kayembe et al. Now, part of our research was concerning the synthesis 2010). Malaria endemic areas include Africa, South East Asia, and biological activity of 1,10-phenanthroline derivatives.
India and South America; however, the disease is spreading In this program continuation of these studies, we report in to new areas, such as Central Asia, and Eastern Europe.
this paper our results concerning the synthesis and the Local transmission of malaria in the United States, unheard determination of the biological activity of compound type of in the era between World War II and 1980, now accounts for an increasing number of cases (Molyneux et al. 1989).
(Widjayanti et al. 2006). Yapi et al. (2006) have synthesized Clinical cases in the US now average 1,300 per year diaza-analogs of phenanthrene by substituting the two (Wernsdorfer 1991). Worldwide, the majority of deaths occur nitrogen atoms in the phenanthrene skeleton. Antiplasmodial in children; other high risk groups include pregnant women, activity of series of diaza-analogs of phenanthrene derived refugees, migrant workers, and non immune travelers-over from 3-amino-, 5-amino-, 6-amino-, 8-aminoquinoline and 20 million Western tourists at risk annually (fact sheets from 5-isoquinoline showed that among the molecules evaluated Malaria Foundation International). Although four species the 1,10-phenanthroline skeleton was the most active of the genus Plasmodium cause human malaria, compound in vitro on both chloroquine-resistant (FcB1) P. falciparum is the deadliest and will be the subject of this and chloroquine-sensitive (Nigerian) strain with an IC of about 0.13 μM. Based on the skeleton, (Mustofa et al. 2003) The traditional remedies are no longer effective and have also synthesized thirteen derivatives of 1,10- the incidence of malarial by P. falciparum, the most phenanthroline and evaluated the in vitro antiplasmodial dangerous species of parasite, continues to grow, while some activity (Yapi et al. 2000) and their Quantitative Structure traditional drugs such as chloroquine and its congeners are Activity Relationship (QSAR) Mustofa et al. 2003. The losing their activity due to the increasing multi drug resulting of the QSAR analysis found the best theoretical resistance (Yapi et al. 2000; Yapi et al. 2006). Therefore, it is activity of six new compounds and its was synthesized and essential to find new drugs of anti malaria having a evaluated their in vitro antiplasmodial activity through pharmacological activity higher than of currently available experiment in laboratory.
drugs of anti malaria. In this connection, quantitative This study were synthesized of 2-phenyl-1,10- structure-activity relationship (QSAR) analysis plays an phenanthroline 5 derivatives from 8-aminoquinoline 4 as
important role to minimize trial and error in designing new starting material were obtained two compounds of 2-phenyl- antimalarial drugs.
1,10-phenanthroline 5 derivatives i.e. (1)-N-methyl-9-phenyl-

Synthesis and antimalarial activity 59 1,10-phenanthrolinium sulphate 6 and (1)-N-ethyl-9-phenyl-
500 MHz. MS spectrum were recorded on GC-MS Shimadzu 1,10-phenanthrolinium sulphate 7 which were synthesized
through 3 stages reaction. The reactions condition and the Procedure. Synthesis of Cinnamaldehyde (3). Ethanol
results of synthesis of 2-phenyl-1,10-phenanthroline 5
(15 mL) was transferred into a 125-mL Erlenmeyer flask, and derivative compounds were described in Figure 1.
20 mL of 10% NaOH solution. Using a thermometer, cool the solution to 20ºC. In a medium size tube, mix 2 mL of MATERIALS AND METHODS
benzaldehyde with 15 drops of acetaldehyde, and leave it at Materials. The 8-aminoquinoline p.a. (Merck),
room temperature for 5 minutes. Then, add the mixture to the dymethyl sulphate (DMS) p.a. (Merck), dymethyl sulphate ethanol-NaOH solution in small portions and stir with (DES) p.a. (Merck), H SO 70% p.a. (Merck), acetaldehyde magnetic stirrer for 30 minutes. Cool the mixture using the p.a. (Merck), benzaldehyde p.a. (Merck), HCl p.a. (Merck), ice-water bath. The product was filtrated and hand-dried to NaOH p.a. (Merck), NaI p.a. (Merck), KOH p.a. (Merck), collect the yellow oils to give of the cinnamaldehyde 3
Na SO anhydrous p.a. (Merck), HBr p.a. (Merck), NaHCO product (6.09 g; 92.04%). The product was characterized by p.a. (Merck), acetone p.a. (Merck), CH Cl p.a. (Merck), CHCl means of spectrum. IR spectrum (KBr) ύ (cm-1): 3062.7-3031.9 p.a. (Merck), CCl p.a. (Merck), dimethyl sulfoxide (DMSO) (HC=), 2927.7 (-C-H), 1685.7 (C=O), 1600.8 and 1462.8 (C=C p.a. (Merck), gas N , Na SO p.a. (Merck), TLC plat, silica aromatic); NMR spectrum (60 MHz, DMSO-d , TMS) gel, hexane p.a. (Merck), benzene p.a. (Merck).
δ (ppm): 10.1 (1H, s, CHO), 8.2-7.9 (3H, m, H Instruments. The melting point of compound were
7.3 (4H, m, H ). MS spectrum (EI) m/z: 132 (M), 131 (M- determined with melting point electro thermal 9100. The .H), 103 (131-C=O), 77 (103-C H ), and 51 (77- C H ).
spectrum of structures compound measurements were taken Synthesis of 2-phenyl-1,10-phenanthroline (5). The
using the instruments: Shimadzu FTIR-8201 PC; 1H-NMR cinnamaldehyde 3 compound (2.64 g; 20 mmol) was added
JEOL 60 MHz, JEOL 500 MHz and GC-MS Shimadzu QP over 5 h to a stirred solution of the 8-aminoquinoline 4
5000. In general, the melting point of compounds were (1.73 g; 10 mmol) and NaI (12 mmol) in H SO 70% (5 mL) at determined on melting point electro thermal 9100 and are 110oC. After 1 h at 110oC the dark brown reaction mixture was not corrected. The spectrum of structures compound cooled to room temperature, poured into 1 M Na CO measurements were taken using the following instruments: (50 mL) and extracted with CH Cl (3 x 50 mL). The FTIR spectrum were taken on Shimadzu FTIR-8201 PC; 1H- combination of organic layers were extracted with CH Cl .
NMR spectrum were obtained on JEOL 60 MHz and JEOL Removal of the solvent in vacuo afforded the appropriate 1,10-phenanthroline skeleton. The products were purified by filtration through silica gel using CH Cl as solvent to give brown solid compound of 2-phenyl-1,10-phenanthroline 5 (2.80 g, 54.63%, m.p.: 145-148oC. The product was
characterized by means of spectrum. IR spectrum (KBr) ύ (cm-1): 3409.9 (O-H hydrogen bonding), 3028.0 (HC=), 2900.0- 2854.5 (-C-H), 1596.9 and 1462.8 (C=C aromatic); NMR spectrum (500 MHz, DMSO-d6, TMS) δ (ppm): 8.30-6.43 (12H, m, Ph); MS spectrum (EI) m/z: 256 (M), 230 (M-C H ), 204 (230-C H ), 179 (204-C H ), 127 (179-NC H ), 101 (127- .C H) and 77 (102-.C H).
rolinium sulphate (6). The 2-phenyl-1,10-phenanthroline 5
(0.51 g; 2 mmol) and DMS (1.26 g, 20 mmol) in acetone (20 mL) was refluxed for 17 h. The resulting mixture was then cooled. The precipitate which formed was filtered, and Recrystalization Figure 1 Synthesis of 2-phenyl-1,10-phenanthroline 5 derivatives
dichloromethane:diethyl ether (1:1). The precipitate which 60 Jurnal Natur Indonesia 15(1): 57–62 Hadanu, et al. formed was filtered and washed with acetone to give brown The parasite control in the presence without chemicals solid compound (0.58 g; 90.62%) of (1)-N-methyl-6-nitro- (mean of the corresponding wells was referred to as 100%).
1,10-phenanthrolinium sulphate 6; m.p.: 188-190oC. The
Concentrations inhibiting 50% of the parasite (IC ) were product was characterized by spectroscopy method. IR
determined by SPPS 13.0 software. The IC that indicated spectrum (KBr) ύ (cm-1): 3429.2 (O-H hydrogen bonding), antiplasmodial activity of chemicals compound to determine 2950.9; 2923.9; and 2866.0 (-C-H), 1600.8 and 1500.0 (C=C by probit analysis method with percentage of concentration aromatic); 1365.5 (CH ); NMR spectrum (500 MHz, DMSO-
inhibition versus chemical doses.
d , TMS) δ (ppm): 9.37 (1H, d, H ), 9.10 (1H, d, H ), 8.75-8.74 (1H, t, H ), 8.58-8.54 (1H, d, H ), 7.94-7.93 (1H, d, H ), 7.83- RESULTS AND DISCUSSION
7.82 (1H, d, H ), 7.76-7.72 (1H, d, H ), 7.68-7.64 (1H, s, H ), The synthesis of 2-phenyl-1,10-phenanthroline 5
7.50-7.30 (1H, t, H ), 7.21-7.13 (1H, t, H ), 6.94-6.92 (1H, t, derivate was carried out through three steps (Figure 1). The H ), 6.80-6.75 (1H, t, H ), 4.78 (3H, s, CH ), and 3.57-3.49
first step is synthesis of cinnamaldehyde 3 compound by
(H O, s; hydrogen bonding).
aldol condensation reaction. This reaction used sodium hydroxide (NaOH) as base catalyst. The condensation of linium sulphate (7). The 2-phenyl-1,10-phenanthroline 5
acetaldehyde with benzaldehyde to give cinnamaldehyde 3
(0.51 g; 2 mmol) and DES (0.51 g; 20 mmol) in acetone compound as product of reaction (6.09 g; 92.04%). The (25 mL) was refluxed for 19 h. The resulting mixture was then second step is synthesis of 2-phenyl-1,10-phenanthroline 5
cooled. The precipitate which formed was filtered, and from 8-aminoquinoline 4 and cinnamaldehyde 3 through
washed with acetone. Recrystalization with dichloromethane: cyclization reaction. The third step is synthesis of the (1)-N- diethyl ether (1:1). The precipitate which formed was filtered alkyl-9-phenyl-1,10-phenanthrolinium salts compound from and washed with acetone to give brown solid compound 2-phenyl-1,10-phenanthroline 5 using DMS and DES reagent
(0.61 g; 89.70%) of (1)-N-ethyl-6-nitro-1,10-phenan- as donor of (1)-N-methyl-9-phenyl-1,10-phenanthrolinium throlinium sulphate 7; m.p.: 188-190oC. The product was
characterized by means of spectroscopic. IR spectrum (KBr)
sulphate 7 compounds (Figure 1).
ύ (cm-1): 3438.8 (O-H hydrogen bonding), 3058.9 (C -H), Synthesis of (1)-N-methyl-9-phenyl-1,10 phenanthro- 2989.5 and 2879.5 (-C-H), 1625.9 and 1525.6 (C=C aromatic); linium sulphate 6 was conducted from 2-phenyl-1,10-
1438.8 (CH ), and 1357.8 (CH ); NMR spectrum (500 MHz,
phenanthroline 5 by DMS reagent in acetone which refluxing
DMSO-d , TMS) δ (ppm): 9.20-8.20 (12H, H ), 2.49 (3H, m, 17 hours. The structure of (1)-N-methyl-9-phenyl-1,10- ) and 1.1 (3H, t, H phenanthrolinium sulphate 6 was determined by FTIR and
Biological Activity. Parasites were cultured according
1H-NMR spectrum. The FTIR spectrum showed typical to method described by Trager and Jensen (1976) with spectra at 1357.8 cm-1 that to indicate the presence of methyl modification. FCBr3 was considered as a chloroquine group, while the 1H-NMR spectrum showed one singlet at resistant strain and D10 were considered as a chloroquine 4.78 (3H), assigned to the methyl group. Treatment of (1)-N- sensitive strain. Culture medium was replaced daily and the ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 compound
cultures were synchronized by 5% D-sorbitol lysis (Merk, with DES in acetone which refluxing for 19 hours gave the Darmstadt, Germany). The method used for in vitro salt compound. The product of ethylation of reaction antimalarial activity testing was adapted from visual method.
washing with acetone and the structure was determined by The molecules were tested 3 times in triplicate in 96-well FTIR and 1H-NMR spectrum. Similarly, the FTIR spectrum plates (TPP, Switzerland) with cultures at ring stage at 0.5-1.0% parasitemia (hematocrit 1%). For each test, the showed typical spectrum at 1438.8 and 1357.8 cm-1, parasite cultures were incubated with the chemicals respectively, assigned to the methyl and methylene groups, at decreasing concentrations for 24 and 72 h. The first while the 1H-NMR spectrum of (1)-N-ethyl-9-phenyl-1,10- dilution of the product (10 mg/mL) was perfomed with phenanthrolinium sulphate 7 compounds showed one triplet
dimethylsulfoxide (DMSO, Merck), and the following with at 2.49 (3H, m, H ) and 1.1 (3H, t, H ), respectively, RPMI 1640. Parasites growth was estimated by coloring with that indicated the presence of methyl and methylene groups.
giemsa (10%) for 30 second and calculated by β-caunter.
Widjayanti et al. (2006) reported the activities of 8 new Synthesis and antimalarial activity 61 Table 1 Parasite growth inhibition and IC of 2-phenyl-1,10-phenanthroline on FCR-3 strain % Inhibition (mean ± SD) Compound of 5
Compound of 6
Compound of 7
Table 2 Parasite growth inhibition and IC of 2-phenyl-1,10-phenanthroline on D10 strain Concentration (ng/mL) % Inhibition (mean ± SD) Compound of 5
Compound of 6
Compound of 7
ND : Not Determined compounds of N-alkyl- and N-benzyl-1,10-phenanthrolinium tively. The result of antiplasmodium evaluation to all 2- derivatives: 1) (1)-N-methyl-1,10-phenanthrolinium sulphate, phenyl-1,10-phenanthroline derivatives toward FCR 3 and 2) (1)-N-ethyl-1,10-phenanthrolinium sulphate, 3) (1)- D10 strain of P. falciparum were presented in Table 1 and 2, N-t-buthyl-1,10-phenanthrolinium chloride, 4) (1)-N- completely. Based on the Table 1 and 2 showed having the benzyl-1, 10-phenanthrolinium chloride, 5) (1)-N-benzyl-1, highest antiplasmodial activity in FCR3 strain is (1)-N- 10-phenanthrolinium bromide, 6) (1)-N-benzyl-1,10- ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 to equal
phenanthrolinium iodide, 7) (1)-N-(4-methoxybenzyl-1,10- 0.13 ± 0.02 µM, while in the D10 strain having the highest phenanthrolinium chloride, and 8) (1)-N-(4-benzyloxy-3- antiplasmodial activity is (1)-N-methyl-9-phenyl-1,10- phenanthrolinium sulfate 6 to equal 0.10 ± 0.04 µ M.
In another compound, Hadanu et al. (2007) reported the This treatment with 2-phenyl-1,10-phenanthroline activities of 1 new compound of (1)-N-(4-methoxybenzyl- derivative compounds significantly inhibited parasitemia of 1,10-phenanthrolinium bromide. All compounds tested P. falciparum FCR3 strain D10 strain (Table 1 and 2).
antiplasmodial activities, the compound of (1)-N-benzyl-1,10- Although the suppression of parasitemia was never phenanthrolinium bromide had the highest activities (0.10 ± complete (100% inhibition of parasite growth), the results 0.13 µM) against P. falciparum strain FCR3 and the (1)-N- indicated antiplasmodial potency. In the P. falciparum FCR3 benzyl-1,10-phenanthrolinium bromide had highest activity strain, the (1)-N-ethyl-9-phenyl-1,10-phenantrolinium sulfate (IC : 0.33 ± 0.34 µM) on P. falciparum strain D10.
7 compound have higher activity than (1)-N-methyl-9-
In this research, the result of evaluation antiplasmodial phenyl-1,10-phenanthrolinium sulphate 6 and 2-phenyl-1,10-
activities using chloroquine-resistant FCR3 strain is phenanthroline 5 compound, but in the P. falciparum D10
summarized in Table 1. While, the result of investigation antiplasmodial activities using chloroquine sensitive D10 sulphate 6 compound have higher activity than (1)-N-ethyl-
strains is summarized in Table 2. In this study, the 9-phenyl-1,10-phenanthrolinium sulphate 7 and 2-phenyl-
antiplasmodial activity of 1,10-phenanthroline derivatives 1,10-phenanthroline 5 compound.
showed that 2-phenyl-1,10-phenanthroline 5, (1)-N-methyl-
9-phenyl-1,10-phenantrolinium sulphate 6, and (1)-N-ethyl-
9-phenyl-1,10-phenantrolinium sulphate 7 were active
The 1,10-phenanthroline derivative compounds i.e. 2- against P. falciparum FCR3 with an IC 2.45 ± 0.09, 0.25 ± 0.01 and 0.13 ± 0.02 µM, respectively, and D10 strains with phenanthrolinium sulphate 6 and (1)-N-ethyl-9-phenyl-1,10-
an IC 0.55 ± 0.07, 0.10 ± 0.04, and 0.18 ± 0.01 µM, respec- phenanthrolinium sulphate 7 were synthesized,
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Kazadi, T.K. 2010. In vitro anti-malarial activity of 20


Advances in diagnostic and therapeutic ultrasound imaging

C H A P T E R 3 3-D US Imaging of the Carotid Arteries Aaron Fenster, Grace Parraga, Anthony Landry, Bernard Chiu, Michaela Egger,and J. David Spence Determining the severity of carotid atherosclerotic stenosis has been an importantstep in establishing patient management pathways and identifying patients who canbenefit from carotid endarterectomy versus those who should be treated using life-style and pharmaceutical interventions. Recently a number of research groups havedeveloped phenotypes other than carotid stenosis using noninvasive imaging. Mon-itoring carotid plaque progression/regression and identifying vulnerable orhigh-risk plaques that can lead to thrombogenic events using noninvasive imagingtools now involve multiple disciplines and multiple modalities, including imageprocessing.

Technology Innovation Management Review TIM Lecture Series The Expanding Cybersecurity Threat It used to be that not a month would go by without some new data breach being reported. Then it seemed not a week would go by. Today, we see daily reports about some new attack vector, some new cyber- espionage group, some new kind of cyber-attack occurring against our