Antiparasitics
= compounds used for treatment of parasitary infestations
1. Antoprotozal drugs
2. Anthelmintics
3. Insecticides, ixodecides and repellents
© assoc. prof. Oldřich Farsa, Ph.D. 2012
1. Antiprotozoal drugs
= compounds killing pathogenic protozoa
1.1. Antimalarial drugs
•infectious agents – protozoa of the genus Plasmodium: P. vivax, P. falciparum, P.
malariae, P. ovale
N
OH
O
N
H
H
quinine
•isolation from cinchona bark Cortex chinae (+ its stereoisomers quinidine,
cinchonine, cinchonidine)
•except antimalarial effects has also antirheumatic and antipyretic ones
•„lead compound“ for design of newer antimalarials with quinoline skeleton
Antimalarial drugs
Quinoline derivatives
N
NH
X
CH3
N CH3
R
1
X = Cl R1
= H chloroquine
Delagil®
tbl.
X = F R1
= H fluoroquine
X = Cl R1
= OH hydroxychloroquine
Plaquenil®
drg.
•also treatment of rheumatoid arthritis
•mech. of action: inhibition of transformation of heme, which is toxic for the parasite, into
hemozoine, which is not ( = „malarial pigment“ - non-toxic for Plasmodium)
Antimalarial drugs
Quinoline derivatives
N
F F
F
OH
F
F
F
NH
H
NH
N
O
NH2
mefloquine
Lariam®
tbl.
•also prophylactic before a
travel to a tropic region
primaquine
Primaquine®
tbl. obd.
Antimalarial drugs
Quinoline derivatives
N
O
NH
N
NCl
NH
Cl
N
H
OH
sitamaquine
tebuquine
Antimalarial drugs
Pyrimidine derivatives
pyrimethamine
Daraprim®

also treatment of toxoplasmosis in
combination with sulfadiazine
N
N NH2
NH2
Cl
O
O
O
CH3
CH3
N
NH2
N
CH3
NH2
trimethoprim
Triprim ® tbl.

now more frequently used in
antibacterial combinations with
sulfonamides
Antimalarial drugs
Biguanide derivatives
proguanil
Malarone®
por. tbl. flm.
•spectrum: P. falciparum
•mech. of action: inhibition of dihydrofolate reductase
•avoids formation of tissue schizonts (hypnozoites)
Cl
N
H
N
H
N
H
CH3
CH3NH NH
Antimalarial drugs
Artemisinin and its analogues

cyclic endoperoxides

mech. of action: forming of free radicals, toxic for
Plasmodium, catalyzed by Fe of heme
O
O
O
O
CH3
H
CH3
H
H
CH3
O
OH
O
O
O O
O
H
CH3
H
H
CH3
O
O
CH3
artemisinin
•sesquiterpene lactone isolated from
wormwood Artemisia annua
•poor biological availability
artesunate
•used as sodium salt for i.m. administration
Antimalarial drugs
Sulfones
NH2
S
O O
NH2
dapson
1,1´-bis(4-aminophenyl)sulfone

mode of action: inhibition of folic acid synthesis, inhibition of
dihydropteroate synthase (like sulfonamides) in particular

also drug for leprosy
1.2 Antiprotozoal drugs other than antimalarials
5-nitroimidazole derivatives
metronidazole
Entizol®
tbl., tbl. vag.
•spectrum: Trichomonas
vaginalis, Entamoeba
histolytica, Treponema,
anaerobic bacteria
•mechanism of action:
interference with metabolism
ornidazole
Avrazor®
inj.
•spectrum: Trichomonas
vaginalis, Entamoeba
histolytica, Giardia intestinalis,
Bacteroides, anaerobic bacteria
mechanism of action:
interference with metabolism
N
N
CH3O2N
OH
N
N
CH3O2
N
OH
Cl
1.2 Antiprotozoal drugs other than antimalarials
Sulfonamides
S
NH
N
N
O
ONH2
S
NH N
N
O
ONH2
CH3
CH3
sulfadiazine

One of the short-acting sulfonamides
used in combination with pyrimethamine to
treat toxoplasmosis in patients with
acquired immunodeficiency syndrome and
in newborns with congenital infections.
sulfadimidine
syn. sulfamethazine [USP]

sodium salt against coccidiosis
(caused namely by Eimeria sp.)
in poultry and rabbits
SULFADIMIDIN BIOVETA ® plv.
sol. ad us. vet.

mode of action: inhibition of dihydropteroate synthase
2. Anthelmintics
= compounds against parasitic worms
Benzimidazole derivatives
N
H
N
N
S
tiabendazole
syn. thiabendazole [USAN, BAN]
Mintezol®
tbl.
•also fungicidal effect
2. Anthelmintics
Benzimidazole derivatives
Methyl 1H-benzimidazole-2-carbamates
•mech. of action: selective inhibition of mitosis of both worms and protozoa
(binding to tubuline)
mebendazole
Vermox®
tbl., por. sus.
N
N
H
N
H
O
O
O CH3
N
N
H
N
H
O
O CH3
S
CH3
albendazol
Zentel®
por. sus.

spectrum: human pinworm Enterobius vermicularis, whipworm Trichuris trichiura,
human large roundworm Ascaris lumbricoides, hookworm Ancylostoma duodenale,
threadworm Strongyloides strercoralis, tapeworms Taenia spp. etc., also protozoa
Girardia lamblia, Trichomonas vaginalis
Anthelmintics
Imidazothiazole derivatives
levamisole
S-(-)-2,3,5,6-tetrahyro-6-phenylimidazo[2,1-b]thiazole
Decaris®
tbl.
•ascaridosis, ancylostomosis, strongyloidosis, trichuriosis
•also immunomodulation effect – useful in rheumatoid
arthritis, lupus erythematodes
N
N
S
H
Anthelmintics
Quinoline derivatives
N
CH3
CH3
N
+
CH3
N
CH3
CH3
X
pyrvinium
Pyrvinium®
susp. as embonate, i.e. salt with 4,4-methylenebis(3-hydroxynaphtalene-2-
carboxylic)acid

human pinworm Enterobius vermicularis
Pyrvinium embonate
OH
O
O
OH
O
O
N
N
+
CH3
CH3
CH3
NCH3
CH3
N
N
+
CH3
CH3
CH3
NCH3
CH3
•pyrvinium embonate (syn. pamoate)
Anthelmintics
Tetrahydropyrimidine derivatives
pyrantel
S
N
N
CH3
1-methyl-2-[(E)-2-(thiophen-2-yl)ethenyl]-1,4,5,6-tetrahydropyrimidine

mechanism of action: depolarizing neuromuscular-blocking agent, that causes
persistent nicotinic activation resulting in spastic paralysis of susceptible
nematodes

drug of second-choice after benzimidazoles for
treatment of ascariasis, hookworm, and pinworm infections

effective after a single dose
Anthelmintics
Pyrazinoisoquinoline derivatives
H
N
N O
O
2-(cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one
praziquantel

treatment of schistosomiasis (blood-flukes or bilharzia or Schistosoma infection)
Anthelmintics
Halogenated salicylanilides
N
H
O
OH
Cl
Cl
O2N
N
H
O
OH
Cl
Cl
Cl
OH Cl
Cl
niclosamide

tapeworms
oxyclozanide

veterinary medicine: for fasciola (liver
fluke) and tapeworms
infestations in grazing animals (cattle)
Anthelmintics
Halogenated salicylanilides
N
H
O
OH
Br
BrBr
tribromsalan
3. Insecticides
Chlorinated compounds
Cl
ClCl
ClCl
Cl
Cl
Cl
Cl
Cl
Cl
DDT
•fundamental importance for eradication of stings
which spreaded malaria and yellow fever
•accumulated in organism and in the
environment ⇒ not used any more
γ-hexachlorocyclohexane
lindan
Skabicid®
drm. eml.
•spectrum: Sarcoptex scabiei,
Phtirius pubis, louse
Pediculus capitis
•topical treatment of scabies
•contact, alimentary and inhalation neural poisons for insects
Cl
Cl
ClH
H
O
Cl
Cl
Cl
Insecticides
Chlorinated compounds
dieldrine
•mechanism of action: inhibition of GABA-receptors
•obsolete: resistance, residues in environment
Insecticides
Organic compounds of phosphorus
Esters of (thio)phosphoric acid & (thio)phosphonic acids
P
O
OO
R
3
R
2
R
1
Y
P
O
O
R
3
R
2
Y
R
4
Y= O, S
R1
- R4
= alkyl, aryl
organophosphates,
organophophothioates
organophosphonates,
organophosphothionates
•irreversible cholinesterases inhibitors ⇒ strong parasympathomimetics
Insecticides
Organic compounds of phosphorus
Esters of phosphoric acid & phosphonic acids
P O
O
Cl
ClO
CH3 O
CH3
P O
O
Cl
ClO
CH3 O
CH3
Cl
OH
dichlorvos
Nuvan Top®
spray a.u.v.
metriphonate
syn. trichlorfon [USAN]
Arpalit®
spray a.u.v.

against fleas in furs (hair) of dogs and cats
Insecticides
Organic compounds of phosphorus
Esters of thiophosphoric acid & thiophosphonic acids
O
CH3
P O
CH3
O
S
S
NH2
O
O
N
CH3
CH3
CH3
PO
CH3
O
CH3
S
cythioate
Cyflee®
sol. a.u.v.
dimpylate
syn. diazinon
Droplix®
a.u.v.
•transcutaneously absorbed, kills
parasites on whole body surface
Insecticides
Selective inhibitors of GABA-receptors
NH2
N
N
Cl
Cl
F
F
F
N
S
O
F
F
F
fipronil
•blocks GABA-receptors of insects which basically differs from mammalian ones in
both structure and function
•highly selective toxicity for insects
Certifect ® „spot-on“ pipettes (+ (S)-methoprene and amitraz) against ticks, fleas
and chewing lice in dogs
methoprene

juvenile hormone analogue and insect growth regulator used to control insects by
disrupting metamorphosis

absorbed into flea eggs or larvae, where it stops their development

effective also in controlling mosquito larvae
Certifect ®
Insecticides
Insect hormone analogues
H
O
CH3
CH3
O
CH3
CH3
O
CH3
CH3
CH3
Ixodecides

kill ticks (arthropods)
CH3 CH3
N N N
CH3
CH3CH3
N'-(2,4-dimethylphenyl)-N-{(E)-[(2,4-dimethylphenyl)imino]methyl}-N-methylimidoformamide
1,5-bis(2,4-dimethylphenyl)-3-methyl-1,3,5-triazapenta-1,4-diene
amitraz

mode of action: stimulates the nervous systems of ticks, leading to hyperactivity and
death of them.
Certifect ®
Repellents
NO
R
CH3
CH3
N
CH3
CH3
O
R = H
N,N-diethylbenzamide
R = CH3
N,N-diethyl-m-toluamide
(= 3-methylbenzoic acid diethylamide)
N-butylacetanilide
(= N-butyl-N-phenylacetamide)
•only repel, do not kill insects and ticks
•used in repellent gels, creams and lotiones in concentrations 10 – 20 %