10.1016/j.steroids.2010.04.002
The research focuses on the synthesis and preliminary biological screening of a new family of sterol analogues, known as azasterols, which possess two amidic bonds on the side chain. These compounds were synthesized using a Ugi four-component reaction (U-4CR), a multicomponent reaction that efficiently incorporates a polyfunctionalized side chain into the steroidal framework. The reactants used in the synthesis included steroidal acids, amines, formaldehyde, and isonitriles. The synthesized compounds were then subjected to antifungal activity testing against two plant pathogenic fungi, Fusarium virguliforme and Fusarium lateritium, using direct bioautography on TLC and minimum inhibitory concentration (MIC) measurements. The structures of the new compounds were confirmed through NMR experiments and mass spectrometry, with the NMR spectra indicating the presence of mixtures of two conformers due to the cis-trans rotation around the N-substituted side chain amide bond. The study demonstrated that some of these novel azasterols exhibit significant antifungal activity, potentially through the inhibition of sterol 24-methyl transferase, an enzyme crucial for ergosterol biosynthesis in fungi.
