ČERNÁ, L., BILDZIUKEVICH, Uladzimir, RÁROVÁ, Lucie, TRYLČOVÁ, Jana, ŠAMAN, David, WEBER, Jan, LOVECKÁ, P., WIMMER, Zdeněk. Oxime derivatives of betulonic acid and platanic acid as novel cytotoxic or antiviral agents. Reaction Chemistry & Engineering. 2024, 9(5), 1087-1095. ISSN 2058-9883. E-ISSN 2058-9883

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 mu M, SI = 2.4) and G-361 (IC50 = 21.3 +/- 2.8 mu M, 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 mu M, SI > 31) and no anti-HSV-1 effect (EC50 > 100 mu M), while platanic acid oxime (15) showed lower effects, EC50 = 36 +/- 4.0 mu M (HIV-1) and EC50 = 48 +/- 6.0 mu M (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 mu M (HIV-1) and EC50 = 12 +/- 0.21 mu M (HSV-1), while another side product 19 was cytotoxic to HeLa (IC50 = 24.5 +/- 1.8 mu M).