Synthesis, NMR characterization and cytotoxic activity of hybrid spirostanic sapogenins-estradiol dimers

Manuel A Ramos-Enríquez; Josué Vazquez-Chavez; Nimsi Campos-Xolalpa; Salud Pérez-Gutiérrez; Martín A Iglesias-Arteaga

doi:10.1016/j.steroids.2023.109286

Synthesis, NMR characterization and cytotoxic activity of hybrid spirostanic sapogenins-estradiol dimers

Steroids. 2023 Nov:199:109286. doi: 10.1016/j.steroids.2023.109286. Epub 2023 Jul 29.

Authors

Manuel A Ramos-Enríquez¹, Josué Vazquez-Chavez¹, Nimsi Campos-Xolalpa², Salud Pérez-Gutiérrez², Martín A Iglesias-Arteaga³

Affiliations

¹ Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 Ciudad de México, Mexico.
² Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Coyoacán, 04960 Ciudad de México, Mexico.
³ Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 Ciudad de México, Mexico. Electronic address: martin.iglesia@unam.mx.

PMID: 37517593
DOI: 10.1016/j.steroids.2023.109286

Abstract

Four hybrid steroid dimers were obtained by BF₃·Et₂O-catalyzed aldol condensation of acetylated steroid sapogenins with 2-formyl-estradiol diacetate. The structures of the obtained dimers were unambiguously established by NMR. The hybrid dimers 9a (IC₅₀ 18.37 μM) and 9c (IC₅₀ 9.4 μM) with the 5α configuration at the A/B rings junction showed the higher cytotoxicity against HeLa, with selectivity index of 4.36 and 11.8 respectively. The presence of a carbonyl function at position C-12 produced the highest cytotoxic effect, which is in line with our previous reports.

Keywords: BF(3)·Et(2)O-catalyzed aldol condensation; NMR characterization Cytotoxicity; Selectivity index; Steroid sapogenins.