Evidence for the presence of R250G mutation at the ATPase domain of topoisomerase II in an arsenite-resistant Leishmania donovani exhibiting a differential drug inhibition profile

Potential therapeutic targets shared between leishmaniasis and cancer

“…However, the emerging interest on Leishmania TOP II was mainly due to its involvement in the kinetoplast DNA network and its replication. Moreover, TOP II is related to drug resistance in these parasites (Jayanarayan and Dey, 2003 ; Sengupta et al ., 2005 ; Singh et al ., 2009 ). The overexpression of a TOP II-like enzyme activity has highlighted the regulatory function of this putative enzyme in arsenite-resistant L. donovani strains (Jayanarayan and Dey, 2003 ).…”

“…A point mutation, R250G, has been detected in the ATPase domain of the TOP II in arsenite-resistant strain of L. donovani parasite. The variation in the TOP II gene sequence between arsenite-sensitive and -resistant strains is anticipated to be responsible for the varied behaviour of this enzymes in response to antileishmanial/anti-TOP II agents (Singh et al ., 2009 ). As aforementioned, similarly to TOP IB targeting agents, there are two groups of TOP II inhibitors depending of their mode of action, and some of them are even able to target both, type I and type II TOPs (Ray et al ., 1997 ).…”