Microtubules as antiparasitic drug targets

Abstract

The most promising immediate avenues for discovery and design appear to lie in development of novel benzimidazoles for helminth parasites and compounds based on antimitotic herbicides for protozoal parasites. New understanding from functional genomics, structural biology and microtubular imaging will help accelerate the development of completely novel antiparasitic drugs targeting microtubules.

Antivascular and anti-parasite activities of natural and hemisynthetic flavonoids from New Caledonian Gardenia species (Rubiaceae)

“…Repeated chromatographic separations on silica gel column using cyclohexane-dichloromethane and dichloromethanemethanol mixtures of increasing polarity as eluent permitted the isolation of 5,7-dihydroxy-3,3 0 ,4 0 ,6-tetramethoxyflavone (1) (210 mg) and 3 0 ,5,7-trihydroxy-3,4 0 ,5 0 ,6-tetramethoxyflavone (2) (12 mg) from G. oudiepe exudate; 5,7-dihydroxy-3,3 0 ,4 0 ,5 0 ,6-pentamethoxyflavone (3) (170 mg), 4 0 ,5,7-trihydroxy-3,6,8-trimethoxyflavone (6) (10 mg), 4 0 ,5,7-trihydroxy-3,6-dimethoxyflavone (7) (150 mg), santin (5,7-dihydroxy-3,4 0 ,6-trimethoxyflavone) (8) (320 mg), and 3-methoxy-kaempferol (isokaempferide) (12) (155 mg), from G. urvillei exudate. 4,5,9,10,13,14 The methylation reactions were performed in one step by stirring the substrate with dimethyl sulfate (Me 2 SO 4 , 4 equiv.) and 1,8-diazabicyclo [5.4.0]undec-7-en (DBU, 2 equiv.)…”

In Vitro Alterations Do Not Reflect a Requirement for Host Cell Cycle Progression during Plasmodium Liver Stage Infection

“…Unsurprisingly, compounds capable of blocking HepG2 cell cycle progression by interfering with either the cytoskeleton or DNA replication, such as aphidicolin, also directly block the replication of the rapidly developing EEF (29,30). Some cell types, however, are known to respond to the prolonged DNA replication fork stalls induced by extended aphidicolin treatment by arresting permanently in S phase after drug washout, a phenotype termed S-phase stasis (31).…”

In-Vitro Antihelminthic Effect of Ethanol Extract of Black Seeds (Nigella sativa) Against Ascaris suum

“…Alkaloids have the ability to inhibit microtubule polymerization of A. suum which has the function in the growth and movement of cells. This mechanism is similar to benzimidazole which used as chemotherapeutic agents for the treatment of parasitic infection 10 . In addition, black cumin seeds can also inhibit antioxidant enzymes which has role in defense mechanism against oxidants generated by nematode host 8,11 .…”

“…However, the efficacy of ethanol extract of black cumin seeds against A. lumbricoides has not been investigated, whereas in fact black cumin seeds contain alkaloid compounds. Alkaloids have the ability to inhibit microtubule polymerization of A. lumbricoides, so it will make the worm paralyze and eventually dead 10 . Black cumin seeds also have antioxidant lowering effect in the worms which wasa defense mechanism of nematodes against human immune responses 8,11 .…”