Structure – Anti-influenza Type a Activity Relationship among a Series of Nitrogen Lupane Triterpenoids

Abstract

Fifty-one derivatives of lupeol, betulin, betulonic and acanthochlamic acids modified at C3, C20 and C28 of the lupane core including four new ones (37, 49 –51) and forty-seven previously synthesized derivatives (1 – 36, 36 – 48) were screened for their in vitro anti-influenza type A (H1N1, H3N2 and H5N1) activity at the NIAID. The selectivity index (SI) against Flu A for tested triterpenoids ranged from > 20 to 0. Betulonic acid 2-aminopyridinylamide was a leader being active against H1N1, H3N2 and H5N1 with SI > 20, 1.8 and 5.3, respectively. The betulonic acid methoxy- and nitro-substituted benzalhydrazides showed selectivity only against H5N1, while lupeol and 3-oximino-betulonic acid benzalhydrazides were active against three types of Flu A. A-seco-aminoderivatives were more effective than the initial acanthochlamic acid against H1N1, but practically inactive against H3N2, with bis- N-methylpiperazinylamide as a leader in this series. Triterpenoids with a long-chain substituent at C17 containing amide or hydrazide bonds with aromatic or heterocyclic fragments exert positive influence on the activity.