Full text of DOI:10.1016/j.bmcl.2018.03.036

Accepted Manuscript
One-Pot, Multicomponent Synthesis of 2,3-Disubstituted Quinazolin-ones with
Potent and Selective Activity Against Toxoplasma gondii
Carla E. Brown, Tiffany Kong, Claudia Bordón, Robert Yolken, Lorraine Jones-
Brando, James McNulty
PII:
S0960-894X(18)30229-4
https://doi.org/10.1016/j.bmcl.2018.03.036
BMCL 25690
DOI:
Reference:
Bioorganic & Medicinal Chemistry Letters
To appear in:
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Accepted Date:
5 March 2018
15 March 2018
Please cite this article as: Brown, C.E., Kong, T., Bordón, C., Yolken, R., Jones-Brando, L., McNulty, J., One-Pot,
Multicomponent Synthesis of 2,3-Disubstituted Quinazolin-ones with Potent and Selective Activity Against
Toxoplasma gondii, Bioorganic & Medicinal Chemistry Letters (2018), doi: https://doi.org/10.1016/j.bmcl.
2018.03.036
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One-Pot, Multicomponent Synthesis of 2,3-Disubstituted
Quinazolin-ones with Potent and Selective Activity Against
Toxoplasma gondii
Carla E. Browna, Tiffany Konga, Claudia Bordónb, Robert Yolkenb, Lorraine Jones-Brandob, James
McNultya*
a Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada L8S 4M1. E-
mail: jmcnult@mcmaster.ca; Tel: (+1)-905-525-9140, Ext. 27393
b Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of
Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
the parasite in vitro and thus is the primary target of
our initial drug development experiments.
ABSTRACT: The discovery of two quinazolinones
with selective, single-digit micromolar activity (IC50
= 6 - 7µM) against the tachyzoites of the
apicomplexan parasite Toxoplasma gondii is
Uninhibited, tachyzoites infect host cells, multiply
until they egress from and lyse the cells, invade nearby
susceptible cells, and then begin the process again
until the entire cell monolayer is lysed. This is known
as the lytic cycle1a.
reported.
These potent and selective third
generation derivatives contain a benzyloxybenzyl
substituent at C2 and a bulky aliphatic moiety at
N3.
Here we show that these quinazolinones
Toxoplasma infection is very common with about 50%
of the world’s human population harboring a
inhibit T. gondii tachyzoite replication in an
established infection, but do not significantly affect
host cell invasion by the tachyzoites.
persistent,
ordinarily
asymptomatic
infection.
However, in developed countries, toxoplasmosis is the
second leading cause of death due to food-borne
illness.1 Further, acute toxoplasmosis as well as
reactivation of persistent T. gondii infections can be
life-threatening during fetal development and in
immunocompromised individuals.1,2,3 In low-income
countries, chronic T. gondii infection is highly
prevalent among HIV-positive patients, and
reactivation of these persistent infections is a major
cause of mortality in this population.4 Persistent T.
gondii infection has also been associated with
neurological illnesses such as schizophrenia5 and
bipolar disorder,6 and several known anti-psychotic
medications are moderately effective against in vitro T.
gondii tachyzoite growth.7 Current prescribed anti-
parasitic chemotherapies for the treatment of T. gondii
infection are effective against the parasite tachyzoite,
the agent of acute disease, but are not effective in
eliminating the encysted parasite bradyzoites, the
agents of the persistent infection. In addition,
resistance to these drugs is rapidly developing.8
Consequently, there is an urgent need to develop new
anti-Toxoplasma agents.
KEYWORDS: Toxoplasmosis, Toxoplasma gondii,
quinazolinone, multi-component synthesis.
Toxoplasmosis is a life-long infectious disease caused
by the apicomplexan parasite Toxoplasma gondii. In
intermediate hosts, e.g., humans, this obligate
intracellular parasite can be present in both its rapidly
replicating stage, tachyzoites, as well as the slowly
replicating/non-replicating stage, bradyzoites. During
an initial, acute infection tachyzoites invade and then
replicate within a parasitophorous vacuole (PV) inside
host cells and then gradually convert to bradyzoites,
thereby forming tissue cysts.
These encysted
bradyzoites become permanent residents of the host’s
skeletal muscle, cardiac muscle and central nervous
system and thus constitute a persistent (latent or
chronic) infection (for a detailed review see Ref 1a). In
contrast to in vivo infections, the tachyzoite stage is
the predominant and most easily manipulated form of

Quinazolinones contain a heterocyclic core that is
found within both natural products and synthetic
pharmaceuticals. Variously substituted quinazolinones
have demonstrated antiparasitic,9,10 antiviral,11 12,13
,
antifungal,14 antibiotic,15 anticancer,16 17 18 and analgesic
activities,19 illustrating the importance and value of
this molecular scaffold in drug design. Given the
known antiparasitic quinazolinones such as
febrifugine and tryptanthrin, and structurally related
,
,
heterocyclic scaffolds that display antiparasitic
21
activity,20 22 we hypothesized that synthetic access to
2,3-disubstituted quinazolinones might allow the
discovery of novel compounds with activity against T.
gondii. Here we describe the synthesis and structural
optimization of quinazolinones and discovery of
potent and selective in vitro anti-tachyzoite agents
through an iterative structure-activity study.
,
,
The condensation of ortho-amino benzamides with
carbonyls produces quinazolinones in a process
catalyzed by protic acids,23,24 Lewis acids,25 and other
catalysts.26,27 Aldehydes and ketones are common
substrates for this chemistry, but diketones,28 ß-
ketoesters,23 and benzyl alcohols29 can also be used. To
generate quinazolinones from dihydroquinazolinone
intermediates, additional oxidants are sometimes
employed.25 30,31 We previously reported a mild, one-pot
,
multicomponent cyclization for the preparation of 2-
substituted and 2,3-disubstituted quinazolinones
(Scheme 1) and development of potent antiviral (HSV-
1) agents through iterative structure-activity
optimization studies.32 We discovered that the
condensation reaction conducted thermally in DMSO
as solvent led exclusively to the aromatic
quinazolinones in good yield (Scheme 1). On the basis
of the precedents described (febrifugine and
tryptanthrin), the three-component coupling strategy
was used to prepare an initial compound array of nine
quinazolinones (4a-4i; first generation) for initial
screening against in vitro T. gondii (Scheme 2).
Reaction of isatoic anhydride with various aldehydes
and ammonium acetate under the conditions
described, led to the assembly of this collection of N3
unsubstituted quinazolinones.
Scheme 2: Structure of the quinazolinones prepared in
the first (4a-4i) generation, unsubstituted at N-3, and
second generation (5a-5i) containing aryl or hexyl
substituents at N-3.
On the basis of initial results (vide infra), a second
generation of quinazolinones (5a-5i) with substituted
aryl and alkyl substituents at N3 was generated. The
structure (Scheme 2) and antiparasitic activity
relationships (Table 1) of the pooled first and second
generation quinazolinones are discussed together
below.
We routinely perform three different assays to screen
experimental compounds for in vitro activity against T.
gondii tachyzoites7,33,34. These assays determine each
compound’s ability to 1) inhibit establishment of
infection and continued growth of tachyzoites over 5
days, i.e. multiple rounds of the lytic cycle, 2) affect
replication of intracellular tachyzoites in an
established infection over a 24 hour period, or 3) affect
extracellular tachyzoites by inhibition of attachment to
and penetration of tachyzoites through host cell
membranes. Thus these three assays interrogate in
vitro efficacy against the major steps of the lytic cycle
of T. gondii tachyzoites, i.e., invasion of host cell,
replication within the host cell, lysis of host cell and
subsequent spread of infection to surrounding cells.
Scheme 1: Synthesis of 2- and 3-substituted
quinazolinone analogs using CSA and DMSO.

All of the compounds (Scheme 2) were thus subjected
to each of these assays using previously published
protocols.7,33,34 Data reported are compiled from three
independent experiments unless otherwise noted.
CPD
4a
4b
4c
IC50 (µM) IC90 (µM) TD50 (µM) TI
20
50
153
14
121
125
6
6
2
443
4989
281
447
266
225
260
414
81
≥320
≥320
≥320
≥320
305
≥320
≥320
≥320
≥320
≥320
4
Stock solutions (10 mM) of compounds were made in
DMSO and stored at -25°C. All further dilutions for
use in assays discussed below were made with cell
growth medium [Dulbecco’s Modified Eagle Medium
(D-MEM; Thermo-Fisher), 10% fetal bovine serum
(Hyclone), 2 mM L-glutamine, 100 units of penicillin G
and 100 µg streptomycin sulfate per ml].
4d
4e
4f
23
12
5
27
56
94
29
92
32
40
4
4g
4h
4i
3
11
3
A detailed, published colourimetric assay protocol
was employed for assessment of
5-day growth
5a
10
8
1
inhibition of both tachyzoites and host cells by the
compounds .7 Briefly, human foreskin fibroblasts
(HFF; ATCC CRL-2088) growing in 96-well tissue
5b
5c
91
14
5d
5e
5f
10
48
42
4
culture plates were treated with
a
range of
concentrations (320-0.032 µM) of the test compounds
or assay positive control atovaquone (ATV; Sigma-
Aldrich; Table 1) or artemisinin (ART; Sigma-Aldrich;
Table 2). Immediately following, purified tachyzoites
from a strain of T. gondii modified to constitutively
express β-galactosidase (β-gal) (RH-2F) were added to
appropriate wells (cf Ref. 7 for details). On the same
96-well plate, uninfected cells were likewise treated
with test or assay control compounds to assess cell
toxicity. A single compound was tested per 96 well
plate; three independent experiments were performed
for each compound. Each plate contained untreated
infected and uninfected cells for reference purposes for
calculation of IC50, IC90, and TD50 (vide infra). Plates
were incubated for four days and then the β-gal
substrate, chlorophenol red-β-D-galactopyranoside
(CPRG; Roche) was added to each Toxoplasma-
infected well. In the presence of live T. gondii
expressing β-gal, this substrate is hydrolyzed to
chlorophenol, which can be detected by monitoring
absorbance at 570-650 nm. Uninfected cells were
treated with a cell viability reagent (CellTiter 96®
Aqueous One Solution; Promega, WI); bioreduction of
this reagent by viable cells can be detected by
absorbance at 490-650 nm. Absorbance data were used
to generate dose-response curves and then the
concentrations required to inhibit 50% and 90% of the
tachyzoite growth, IC50 and IC90 respectively, and the
half-maximal cytotoxic dose, TD50, were calculated
using Calcusyn software (Biosoft, UK) for each
compound (Tables 1 and 2). The therapeutic index, TI,
was derived using the formula TI = TD50/IC50.
60
10
193
45
88
1
178
18
6
7
5g
5h
5i
31
83
196
44
3
126
12
≥320
5
2
ATV
0.2
0.6
21
111
Structure Activity Relationship (SAR) analysis of the
first generation compounds 4a-4i demonstrate that
the electronic and steric nature of the substituent at C2
is important for activity and, importantly, that all
compounds displayed little or no measurable
cytotoxicity (TD50). Electron-rich aryl substituents
mono-substituted at the para-position correlated to
anti-Toxoplasma activity. The most potent compounds
(lowest IC50) had 4-methoxy (4a) and 4-
dimethylamino (4d) substituents at this position. In
contrast, electron withdrawing substituents at the para
position (4e, 4h) or ortho and meta/para substituted
electron donating substituents (4f, 4b) proved to be
less active.
A second generation of compounds 5a-5i was thus
prepared retaining an electron rich aryl substituent at
C2, but now incorporating N3 substitution through
conducting the three-component reaction with
anilines or amines. The nature of the substituent at N3
was also found to significantly affect antiparasitic
activity and in some cases to unfortunately increase
host cell cytotoxicity. Analysis of this SAR disclosed
two interesting features of the pharmacophore. Firstly,
compounds
containing
the
electron
rich
benzyloxybenzyl ether at C2 and an aryl group at N3
(5c, 5i) proved to be potent antiparasitics, however
they also proved toxic to the host HFF cells. Secondly,
compounds containing an alkyl group at N3
Table 1: Anti-Toxoplasma activity of quinazolinones
depicted in Scheme 2.

modulated both potency and host cell cytotoxicity in
concert with substitution. For example, considering
the series 5e, 5d, 5f, antiparasitic activity increased
with the electronic rich nature of the C2 aryl
substituent (as observed above) with 5d (4-OMe) and
5f (4-OBn) showing equal potency. However we could
now differentiate antiparasitic activity from host cell
cytotoxicity through the combination of the C2-
benzyloxy substituent alone, in concert with the alkyl
substituent at N3. Overall, the most potent
compounds in the 5-day growth inhibition assay
proved to be 4d, 5c, 5f, and 5i with IC50 values below 15
µM. Quinazolinones 4d and 5f distinguished
themselves as the most promising candidates overall
from this initial screening in view of both potency and
low host-cell cytotoxicity and encouraged the
preparation of a third generation compound array to
probe the H atom or alkyl substituent at N3, in concert
with para-substituted electron-rich aryl group at C2
(vide infra).
concentration (IC50 = 3 µM) in the 5-day growth
inhibition assay. However, 5i is considerably toxic to
the host HFF (TD50 = 5 µM) resulting in a narrow
window of specific anti-Toxoplasma activity (TI = 2)
thus rendering it less desirable as a lead drug
candidate. 4d and 5f both displayed good potency
and minimal cytotoxicity in the 5-day growth
inhibition assay but did not effectively inhibit
tachyzoite replication. Thus there was no apparent
correlation between growth inhibition and replication
inhibition for active molecules 4d and 5f, suggesting
that inhibition of an established infection is not the
primary mechanism of action for these quinazolinone
derivatives. Due to the general lack of efficacy in
replication inhibition, this assay was not pursued
beyond the primary experiment for 1st and 2nd
generation compounds.
#Tx / vacuole
1.00
0.90
1
0.80
0.70
In addition to determining potency (IC50) and
selectivity (TI) of the quinazolinones, a previously
published replication assay was performed to assess
the ability of each compound to inhibit replication of
2
0.60
0.50
4
0.40
intracellular
tachyzoites
in
an
established
8
0.30
0.20
0.10
0.00
infection.33,Fig.1;34,Fig.2 In this assay, purified tachyzoites are
allowed to invade host cells (HFF) growing on 8-well
cell culture chamber slides (Nunc) and establish an
infection. After 2h test compounds (10 µM) or DMSO
(vehicle) are added to the infected cells. After a further
24h, the monolayers are fixed, permeabilized and
tachyzoites immunolabeled with a rabbit antibody
specific for the tachyzoite surface antigen followed by
fluorescently (red) conjugated anti-rabbit IgG.
Following this the number of parasitophorous vacuoles
(PV) containing 8, 4, 2, or 1 tachyzoites, representing 3,
2, 1 or 0 cycles of replication respectively, observed in
ten random microscopic fields per each well is counted
microscopically by eye. Compounds that restrict
tachyzoite replication to 0 or 1 cycle, displayed as a
predominance of 1 or 2 tachyzoite-sized vacuoles, are
considered inhibitory. The majority of first and second
generation quinazolinones (10 µM) did not inhibit
replication over the 24-hour assay period
(Supplementary Figure S1). For example, Figure 1
displays the replication assay data of the most potent
compounds in the growth inhibition assay, 4d, 5c, 5f,
and 5i, as well as the data of 4i and 5e. As shown in the
graph, only 4i, 5e, and 5i displayed any potential
ability to inhibit replication as evidenced by a larger
fraction of size 1 vs. size 8 PVs. Additionally, treatment
with 5i resulted in >75% of PVs containing just 1 or 2
tachyzoites. Of these three compounds, only 5i also
showed anti-Toxoplasma activity at low micromolar
Figure 1: Replication of T. gondii tachyzoites after
treatment with first and second generation
quinazolinones. Fractions of total number vacuoles
counted containing 8, 4, 2, and 1 tachyzoites are
shown in blue, red, green, and purple
respectively+69 Select compounds shown, for full
results see SI Supplementary Figure 1).
The replication assay described above investigates
the ability of test compounds to affect intracellular
tachyzoites, an established infection within the host
cells. Next, the ability of these quinazolinones to
directly affect extracellular tachyzoites by inhibiting
attachment to and invasion of host cells
interrogated. In the invasion assay (detailed in Ref. 34,
Figure 1), purified, extracellular tachyzoites are
was
incubated with test compounds (10 µM) for 20 minutes
at room temperature and then allowed to invade HFF
host cells growing on 8-well cell culture slides for one
Fig
1
hour.34
Immunofluorescent staining is used to
differentiate and quantify tachyzoites that have
penetrated the host cell (Figure 2, green bars),
tachyzoites that have attached to the host cell but were
unable to penetrate (Figure 2, red bars), and
tachyzoites that began but were unable to complete

host cell invasion (Figure 2, gold bars). A significant
decrease in the number of penetrated (green)
tachyzoites compared to the same of vehicle indicates
inhibition of invasion, while a significant decrease in
the total number of tachyzoites associated with the cell
(green, red, and gold) versus vehicle indicates
inhibition of attachment. The majority (15 of 18) of the
first and second generation derivatives significantly
inhibited tachyzoite invasion and nearly half (8 of 18)
significantly inhibited attachment (SI Figure S2). The
most active compounds identified by growth
inhibition efficacy (4d, 5c, 5f, 5i) inhibited invasion at
10 µM. 4d, 5c, and 5f also inhibited attachment of
tachyzoites to the host cells (Figure 2). In addition, 4i
and 5e, compounds that showed potential inhibition
of replication, significantly inhibited both invasion
and attachment. Thus, in contrast to replication
inhibition, there is an apparent correlation between
the growth inhibition and the invasion inhibition for
active molecules, suggesting that inhibition of host
invasion could be a primary mechanism of action for
these quinazolinones.
or alkyl substituent at N3, in concert with para-
substituted electron-rich aryl group at C2, as a means
to retain potency and mitigate host-cell cytotoxicity.
Thus a third generation of quinazolinones 6a-6m with
varying N3 alkyl-substituents (Scheme 3) was
prepared. These compounds were readily accessed as
described for the first and second generation series
through the three-component condensation of 4-
dimethylaminobenzaldehyde
or
4-
benzyloxybenzaldehyde with a variety of alkyl amines.
The third generation quinazolinone collection was
screened for activity against T. gondii and host-cell
cytotoxicity as described above and results are
summarized in Table 2. The nature of the N3-alkyl
substituent proved to have only a moderate effect on
the magnitude of antiparasitic activity (IC50). However,
more importantly, the N3 alkyl substituent was found
to play a significant role in modulating the host-cell
cytotoxicity (TD50). Derivatives bearing a cyclohexyl
6e, benzyl 6f or geranyl 6j group at N3 demonstrated
potent antiparasitic activity, with no host-cell
cytotoxicity being observed at the highest
concentration investigated (>320 µM). The data
observed for quinazolinones 6b and 6e, both
containing an N3-cyclohexyl substituent, show an
1.8
Invaded
1.6
Mid
1.4
interesting
synergistic
effect
of
the
C2
Attached
benzyloxyphenyl (and not para-dimethylamino) and
N3-alkyl group in mitigating host cell cytotoxicity.
1.2
1.0
**
**
0.8
**
**
**
*
*
*
0.6
0.4
0.2
0.0
*
*
*
VHL
4d
4i
5c
5e
5f
5i
Figure 2: Invasion of tachyzoites into a host cell
after extracellular treatment with first and second
generation quinazolinones. Tachyzoites attached
to the host are shown in red, tachyzoites that have
penetrated are shown in green, and tachyzoites
midway through the invasion process are shown in
gold. The most active compounds identified in the
5-day growth assay (4d, 5c, 5f, 5i) inhibit invasion
(*p ≤ 0.05, two-tailed Student’s t test). Compounds
4d, 5c, and 5f appear to also inhibit attachment (**
p ≤ 0.05) of the tachyzoite to the host. Data are
mean values ± SEM from 3 independent
experiments. Select compounds shown, for full
results see SI Supplementary Figure 2).
The intriguing SAR analyses of the first and second
generation quinazolinones inspired preparation of a
third generation compound array to probe the H atom

infection was determined. Many of these
quinazolinones markedly inhibited replication of
intracellular tachyzoites at 10 µM (SI Figure 3). The
most active third generation compounds in the growth
inhibition assay, 6e, 6f and 6j, also effectively inhibited
intracellular tachyzoite replication as evidenced by
greater than 70% % of PVs containing only 1 or 2
tachyzoites (Figure 3). Each of these compounds
contains a benzyloxybenzyl group at C2, which further
suggests this group is important for the potency of
quinazolinones. These results are consistent with the
5-day growth inhibition assay, which showed
compounds 6e, 6f, and 6j, to be both potent and
selective.
OH
O
N
O
N
O
N
N
N
N
6b
15%
6c
6a
43%
N
N
N
15%
OH
O
O
O
N
N
N
N
N
N
6e
25%
6f
76%
O
6d
49%
O
O
O
O
O
C10H21
N
N
N
N
N
N
6i
24%
6h
34%
O
O
6g
35%
N
#Tx / vacuole
1.00
1
2
4
8
0.90
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
O
O
N
O
C10H21
N
N
N
N
N
6j
36%
6k
45%
O
N
6l
34%
N
O
N
N
N
H
6m
24%
O
Figure 3: Replication of T. gondii tachyzoites after
treatment with third generation quinazolinones 6e,
6f, and 6j. Select compounds shown, for full results
see SI Supplementary Figure 3. See Legend to Figure 1
for complete explanation. Data are compiled from
results of 3 independent experiments.
Scheme 3: Third generation of quinazolinone
derivatives containing para-substituted electron rich
substituents at C2 and varied alkyl groups at N3.
Table 2: Anti-toxoplasma activity of third generation
quinazolinone-based library
When tested in the invasion assay, 6e, 6f, and 6j did
not show statistically significant inhibition of T. gondii
attachment to or penetration of the host cell (Figure
4). Taken together, these results suggest that the target
of these third generation compounds is not involved in
the invasion process, a direct contrast to the first and
second generations. We are currently working to
identify the target of the lead candidates identified
here through the use of affinity or fluorescence probes.
CPD
6a
IC50 (µM) IC90 (µM) TD50 (µM) TI
112
15
12
17
6
353
67
60
52
196
2
6b
6c
112
7
133
11
6d
6e
229
≥320
≥320
50
13
53
25
3
46
71
6f
13
18
25
12
7
6g
6h
6i
52
2.0
Invaded
Mid
Attached
119
55
≥320
118
13
10
46
7
1.8
1.6
1.4
6j
58
170
116
724
19
≥320
≥320
85
1.2
1.0
0.8
0.6
0.4
0.2
0.0
6k
6l
49
35
154
2
2
6m
ART
≥320
≥320
2
160
The ability of these third-generation quinazolinones
to inhibit replication of an established parasitic
VHL
6e
6f
6j

1a
Dubey, J.P.; Lindsay, D.S.; Speer, C.A. Clin.
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Figure 4: Invasion of tachyzoites into a host cell after
treatment with the third generation quinazolinones.
The most active compounds in this set (6e, 6f, and
6j) do not significantly inhibit invasion. Select
compounds shown, for full results see SI
Supplementary Figure 4). See Legend Figure 2 for
complete explanation. Data are mean values ± SEM
from 3 independent experiments
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5.
6.
7.
8.
In conclusion, three iterative generations of synthesis
and antiparasitic activity/host cell cytotoxicity assay of
a quinazolinone library led to the discovery of single-
digit micromolar inhibitors of Toxoplasma gondii that
are non-toxic to the human host cells. The most potent
and selective analogs, 6e and 6j, contain bulky alkyl
groups at N3 and benzyloxybenzyl ether functionality
at C2, structural features that synergistically contribute
to potent and selective antiparasitic activity. While
many other structural combinations can now be
considered, based on the three rounds of SAR
completed, the identified quinazolinones 6e and 6j,
with IC50 values of 6 µM and 7 µM, are important lead
compounds toward the development of novel potent
and selective anti-Toxoplasma agents. Further analysis
and refinement of this new pharmacophore and
exploration of efficacy of these compounds against in
vivo encysted bradyzoites, the persistent form of the T.
gondii infection, to determine utility against latent or
chronic toxoplasmosis are under active investigation in
our laboratories.
9.
10.
11.
12.
13.
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15.
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Acknowledgements
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Lad, L.; Luo, L.; Carson, J. D.; Wood, K. W.; Hartman,
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3576–3585.
We thank the Stanley Medical Research Institute for
support of this work. CEB is the holder of an NSERC
postgraduate fellowship and TK was a recipient of an
NSERC undergraduate student research award. The
following reagent was obtained through the NIH
Biodefense and Emerging Infections Research
Resources Repository, NIAID, NIH: Toxoplasma gondii,
2F (RH-2F), NR-224.
Zhang, G.-H.; Xue, W.-B.; An, Y.-F.; Yuan, J.-M.;.;
Olivieri, P. R.; Boezio, A. A.; Deak, H. L.; Emkey, R.;
Graceffa, R. F.; Gunaydin, H.; Guzman-Perez, A.; Lee,
J. H.; Teffera, Y.; Wang, W.; Youngblood, B. D.; Yu,
V. L.; Zhang, M.; Gavva, N. R.; Lehto, S. G.; Geuns-
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Full details on the synthesis and characterization of
compounds and methods for antiparasitic activity.
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34

One-pot multicomponent synthesis of 2,3-
disubstituted quinazolinones with potent and
selective activity against Toxoplasma gondii
Leave this area blank for abstract info.
Carla E. Brown, Tiffany Kong, Claudia Bordon,
Robert Yolken, Lorraine Jones-Brando, James McNulty,
Inhibition of replication of T. gondii tachyzoites by
compound 6e (10 µM). Eighty percent or more of
PVs contain only 1 or 2 tachyzoites.