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“…Encouraged by those findings, we decided to extend the range of azasterols; some of these compounds were active against bloodstream form Trypanosoma brucei subsp. rhodesiense, the causative organism of human African trypanosomiasis (7,8).…”
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“…Encouraged by those findings, we decided to extend the range of azasterols; some of these compounds were active against bloodstream form Trypanosoma brucei subsp. rhodesiense, the causative organism of human African trypanosomiasis (7,8).…”
mentioning
“…These observations led to the discovery that tipifarnib also inhibits trypanosomal cytochrome P450 sterol 14-demethylase [91]. Sterols related to 35 were found to be excellent growth inhibitors in L. donovanii, L. major, and T. cruzi with relatively low toxicity to host cells [92,93]. It was later determined that compound 35 and its homologs are potent transition state analog inhibitors of 24-sterol methyltransferase from L. major [93].…”
Section: Inhibitors Of Parasitic Lipid Metabolismmentioning
“…Sterols related to 35 were found to be excellent growth inhibitors in L. donovanii, L. major, and T. cruzi with relatively low toxicity to host cells [92,93]. It was later determined that compound 35 and its homologs are potent transition state analog inhibitors of 24-sterol methyltransferase from L. major [93]. Some analogs in the series were also effective against T. b. rhodesiense, although this effect was mediated at a site other than trypanosomal 24-sterol methyltransferase.…”
Section: Inhibitors Of Parasitic Lipid Metabolismmentioning
“…Some azasterols able to inhibit 24-methyltransferase showed antileishmanial activity. However, other compounds of the same family that did not affect the enzyme showed nonetheless antileishmanial activity by a mechanism that still needs to be elucidated [178,179]. Sterols synthesis may also be affected by plant extracts: sterols isolated from the roots of the plant Pentalion andrieuxii showed marked antileishmanial activity [180], as well as the steroidal glycoalkaloid α-tomatine, derived from Lycopersicon aesculentum [181].…”
Section: Target-based Development Of New Drugsmentioning