Anthelmintics - Medicinal Chemistry III B. Pharma 6th Semester


       Anthelmintics are drugs that have the capability of ridding the body of parasitic worms or helminths

       Helminths that infect human hosts are divided into two categories, or phyla:

       a) Platyhelminthes (flatworms)- include the classes Cestode (tapeworms) and Trematode (flukes or schistosomes)

       b) Aschelminthes or nematodes (roundworms)- roundworm, hookworm, pinworm, and whipworm. These worms are cylindrical in shape, with significant variations in size, proportion, and structure

       Nematode Infections

       Ancylostomiasis or Hookworm Infection- American hookworm (Necator americanus) and the “Old World” hookworm (Ancylostoma doudenale).

       Enterobiasis or Pinworm Infection- Enterobius vermicularis

       Ascariasis or Roundworm Infections- Ascaris lumbricoides

       Trichuriasis or Whipworm Infections- Trichuris trichiura

       Trichinosis or Trichina Infection- Trichinella spiralis

       Filariasis- Wuchereria bancrofti, Brugia malayi, and Brugia timori

       Cestode and Trematode Infections

       Cysticercosis or Tapeworm Infection

       Beef tapeworm (Taenia saginata)

       Pork tapeworm (Taenia solium)

       Dwarf tapeworm (Hymenolepis nana)

       Fish tapeworm (Diphyllobothrium latum)

       Schistosomiasis or Blood Flukes- Schistosoma hematobium, Schistosoma mansoni, and Schistosoma japonicum

Diethylcarbamazine citrate

       Highly water-soluble crystalline compound that has selective anthelmintic activity

       It is effective against various forms of filariasis, including Bancroft, onchocerciasis, and laviasis

       It is also active against ascariasis

       Mechanim- not clearly known

       Suggestion- inhibition of microtubule polymerization and disruption of preformed microtubules

       Or interference with arachidonic acid metabolism

       Adverse reactions- anaphylactic reactions, intense pruritus, and ocular complications 


       Occurs as a white crystalline substance that is only slightly soluble in water but is soluble in strong mineral acids.

       Thiabendazole is a basic compound with a pKa of 4.7 that forms complexes with metal ions

       Mechanism- inhibits the helminth-specific enzyme fumarate reductase (important enzyme in helminthes that appears to be involved in oxidation of NADH to NAD for ATP production)

       Also arrest nematode cell division in metaphase by interfering with microtubule assembly and exhibit a high affinity for tubulin, the precursor protein for microtubule synthesis

       Has broad-spectrum anthelmintic activity

       It is used to treat enterobiasis, strongyloidiasis (threadworm infection), ascariasis, uncinariasis (hookworm infection), and trichuriasis (whipworm infection)

       Also used to relieve symptoms associated with cutaneous larva migrans (creeping eruption) and the invasive phase of trichinosis.

       Widely used in veterinary practice to control intestinal helminths in livestock


       Broad-spectrum anthelmintic that is effective against various nematode infestations, including whipworm, pinworm, roundworm, and hookworm

       Mechanism- irreversibly blocks glucose uptake in susceptible helminths, thereby depleting glycogen stored in the parasite

       It apparently does not affect glucose metabolism in the host. It also inhibits cell division in nematodes

       Poorly absorbed by the oral route

       Adverse reactions are uncommon and usually abdominal discomfort

       It is teratogenic in laboratory animals and should not be given during pregnancy


       Broad-spectrum anthelmintic that is not currently marketed in North America

       Widely used throughout the world for the treatment of intestinal nematode infection

       It is effective as a single-dose treatment for ascariasis, New and Old World hookworm infections, and trichuriasis

       Multiple-dose therapy with albendazole can eradicate pinworm, threadworm, capillariasis, clonorchiasis, and hydatid disease

       Effectiveness of albendazole against tapeworms (cestodes) is generally more variable and less impressive

       White crystalline powder that is virtually insoluble in water

       Oral absorption of albendazole is enhanced by a fatty meal

       Drug undergoes rapid and extensive first-pass metabolism to the sulfoxide, which is the active form in plasma

       Elimination half-life of the sulfoxide ranges from 10 to 15 hours

       High dose can result in adverse effects such as bone marrow depression, elevation of hepatic enzymes, and alopecia


       Occurs as a yellowish white, water-insoluble powder

       Potent taeniacide that causes rapid disintegration of worm segments and the scolex

       Penetration of the drug into various cestodes appears to be facilitated by the digestive juices of the host

       Niclosamide is well tolerated following oral administration, and little or no systemic absorption of it occurs

       A saline purge 1 to 2 hours after ingestion of the taeniacide is recommended to remove the damaged scolex and worm segments- mandatory


       Antischistosomal agent that is indicated for the treatment of Schistosoma mansoni (intestinal schistosomiasis) infection

       Mechanism- Shown to inhibit DNA, RNA, and protein synthesis in schistosomes

       6-hydroxymethyl group is critical for activity;

       metabolic activation of precursor 6-methyl derivatives is critical

       Free base occurs as a yellow crystalline solid that is slightly soluble in water but soluble in dilute aqueous mineral acids and soluble in most organic solvents

       Dizziness and drowsiness are common, but transitory, side effects

       Serious reactions, such as epileptiform convulsions, are rare


       Broad-spectrum agent that is effective against various trematodes (flukes)

       It has become the agent of choice for the treatment of infections caused by schistosomes (blood flukes)

       Effective treatment for fasciolopsiasis (intestinal fluke), clonorchiasis (Chinese liver fluke), fascioliasis (sheep liver fluke), opisthorchosis (liver fluke), and paragonimiasis (lung fluke)

       Mechanism- increases cell membrane permeability of susceptible worms, resulting in the loss of extracellular calcium. Massive contractions and ultimate paralysis of the fluke musculature occurs, followed by phagocytosis of the parasite

       Oral administration, about 80% of the dose is absorbed

       Drug is rapidly metabolized in the liver in the first-pass

       White crystalline solid that is insoluble in water


       Is a mixture of 22,23-dihydro derivatives of avermectins B1a and B1b prepared by catalytic hydrogenation

       Avermectins are members of a family of structurally complex antibiotics produced by fermentation with a strain of Streptomyces avermitilis

       Ivermectin is active in low dosage against a wide variety of nematodes and arthropods that parasitize animals

       Structure- pentacyclic 16-membered–ring aglycones glycosidically linked at the 3-position to a disaccharide that comprises two oleandrose sugar residues

       Side chain at the 25-position of the aglycone is sec-butyl in avermectin B1a, whereas in avermectin B1b, it is isopropyl

avermectins B1a (-C2H5) and B1b (-CH3)

       Ivermectin contains at least 80% of 22,23-dihydroavermectin B1a and no more than 20% 22,23-dihydroavermectin B1b

       Widespread use in veterinary practice in the United States and many countries throughout the world for the control of endoparasites and ectoparasites in domestic animals

       It has been found effective for the treatment of onchocerciasis (“river blindness”) in humans, an important disease caused by the roundworm Oncocerca volvulus

       Mechanism- It blocks interneuron–motor neuron transmission in nematodes by stimulating the release of the inhibitory neurotransmitter GABA

Diethylcarbamazine citrate- Synthesis

Mebendazole- Synthesis

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