Oxime derivatives of betulonic acid and platanic acid as novel cytotoxic or antiviral agents

Abstract

Less frequently studied plant triterpenoids betulonic acid and platanic acid were selected to design, synthesize and investigate their oxime derivatives as novel and potentially effective cytotoxic and/or antiviral agents. The target compounds were subjected to cytotoxicity screening tests in several human cancer cell lines. Several of them displayed cytotoxicity against T-lymphoblastic leukemia (CCRF-CEM), breast adenocarcinoma (MCF7), malignant melanoma (G-361) and cervical cancer (HeLa) cell lines. Betulonic acid oxime (3) displayed cytotoxicity against CCRF-CEM (IC₅₀ = 18.9 ± 1.1 μM; SI = 2.4) and G-361 (IC₅₀ = 21.3 ± 2.8 μM; SI = 2.2) cancer cell lines. The benzyl ester of platanic acid oxime (17) displayed an anti-HIV-1 effect (EC₅₀ = 3.2 ± 0.43 μM; SI > 31) and no anti-HSV-1 effect (EC₅₀ > 100 μM), while platanic acid oxime (15) showed lower effects, EC₅₀ = 36 ± 4.0 μM (HIV-1) and EC₅₀ = 48 ± 6.0 μM (HSV-1), respectively. Compound 17 showed high selectivity in antiviral effects, being effective in HIV-1 and inactive in HSV-1. A side product 18 showed antiviral activity with EC₅₀ = 15 ± 1.3 μM (HIV-1) and EC₅₀ = 12 ± 0.21 μM (HSV-1), while another side product 19 was cytotoxic to HeLa (IC₅₀ = 24.5 ± 1.8 μM).