| Abstract
| - This paper describes the synthesis of some novel azasterols based on (20R,22ξ)-5α-pregnan-20-(piperidin-2-yl)-3β,20-diol. These compounds are potential inhibitors of the enzyme sterol24-methyltransferase (24-SMT), which is a vital enzyme in the biosynthesis of ergosterol andrelated 24-alkyl sterols. Structure−activity studies were undertaken to understand theimportant features for activity against the enzyme, with the aim of increasing activity andselectivity. The compounds were evaluated for inhibition of recombinant Leishmania major24-SMT and the effect of compounds on sterol composition and parasite proliferation.Essentially, compounds which showed good activity against the recombinant enzyme had asignificant effect on the sterol composition and growth of parasites. The activity of compoundswas found to be related to the basicity and stereochemical location of the nitrogen. Also, presenceof an unprotected 3β-OH seemed to be important for activity. However, some azasterols whichwere not good inhibitors of 24-SMT also showed antiproliferative activity, suggesting that theremay be other modes of actions of these compounds.
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