J. Howarth, K. Hanlon / Tetrahedron Letters 42 (2001) 751–754
753
Table 2.
When compounds 4a–i and 8a–e were tested for anti-
malarial activity against the Plasmodium falciparum
NF54 strain the compounds were active with IC50s as
given in Tables 1 and 2, respectively. Given that the
IC50s for two of the current drugs used against this
particular strain, chlorquine and artemeter, are 0.02
and 0.025 mM, respectively, these initial results would
indicate that the N-ferrocenylmethyl, N%-methyl-2-aryl
(or styryl) benzimidazolium iodide salts may have
future potential as compounds in the fight against
malaria. To the best of our knowledge these are the first
examples of benzimidazolium salts shown to have activ-
ity against malaria, although clotrimazole has been
shown to have powerful growth inhibiting effects in the
P. falciparum parasite.13 We have included the results
for the same test carried out on the parent N-ferro-
cenylmethyl benzimidazole, compounds 3a–i and 7a–e.
It is interesting to note that the activities for these
non-quaternised compounds are several fold less, which
in our opinion substantiates our hypothesis concerning
the HMS above.
section of the World Health Organisation, Enterprise
Ireland, and Arch Chemicals BV.
References
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The mechanism of the antimalarial activity is unknown,
however mechanisms shown for other imidazole-based
drugs have been related to inhibition of catalase and
peroxidase activities.14 Alternatively a number of azino
fused benzimidazolium salts have been utilised as DNA
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Acknowledgements
thesis of 4a as an example. To a mixture of 2-
phenylbenzimidazole17 1a (2.5 g, 13.0 mmol) and
potassium carbonate (2.7 g, 19.5 mmol) in acetonitrile
(150 ml) was added (trimethylammonium)ferrocenyl-
methyl iodide 2 (10.0 g, 13.0 mmol). The mixture was
The authors would like to acknowledge the contribu-
tion to this research by the Tropical Disease Research