In vitro adjuvant antitumor activity of various classes of semi-synthetic poststerone derivatives

Rimma G Savchenko; Márta Nové; Gabriella Spengler; Attila Hunyadi; Lyudmila V Parfenova

doi:10.1016/j.bioorg.2020.104485

In vitro adjuvant antitumor activity of various classes of semi-synthetic poststerone derivatives

Bioorg Chem. 2021 Jan:106:104485. doi: 10.1016/j.bioorg.2020.104485. Epub 2020 Nov 19.

Authors

Rimma G Savchenko¹, Márta Nové², Gabriella Spengler², Attila Hunyadi³, Lyudmila V Parfenova⁴

Affiliations

¹ Institute of Petrochemistry and Catalysis of Russian Academy of Sciences, 141, Prospekt Oktyabrya, 450075 Ufa, Russia.
² Department of Medical Microbiology and Immunobiology, University of Szeged, Dóm sq. 9, 6720 Szeged, Hungary.
³ Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös str. 6, 6720 Szeged, Hungary; Interdisciplinary Centre for Natural Products, University of Szeged, Eötvös str. 6, 6720 Szeged, Hungary. Electronic address: hunyadi.a@pharmacognosy.hu.
⁴ Institute of Petrochemistry and Catalysis of Russian Academy of Sciences, 141, Prospekt Oktyabrya, 450075 Ufa, Russia. Electronic address: luda_parfenova@ipc-ras.ru.

PMID: 33261846
DOI: 10.1016/j.bioorg.2020.104485

Abstract

Various classes of semi-synthetic analogs of poststerone, the product of oxidative cleavage of the C20-C22 bond in the side chain of the phytoecdysteroid 20-hydroxyecdysone, were synthesized. The analogs were obtained by reductive transformations using L-Selectride and H₂-Pd/C, by molecular abeo-rearrangements using the DAST reagent or ultrasonic treatment in the NaI-Zn-DMF system, and by acid-catalyzed reactions of poststerone derivatives with various aldehydes (o-FC₆H₄CHO, m-CF₃C₆H₄CHO, CO₂Me(CH₂)₈CHO). The products were tested on a mouse lymphoma cell line pair, L5178 and its ABCB1-transfected multi-drug resistant counterpart, L5178_MDR, for their in vitro activity alone and in combination with doxorubicin, and for the ability to inhibit the ABCB1 transporter. Among the tested compounds, new 2,3-dioxolane derivatives of the pregnane ecdysteroid were found to have a pronounced chemosensitizing activity towards doxorubicin and could be considered as promising candidates for further structure optimization for the development of effective chemosensitizing agents.

Keywords: Adjuvant; Chemo-sensitization; Dioxolanes; Ecdysteroids; Multidrug resistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Ecdysterone / chemical synthesis
Ecdysterone / chemistry
Ecdysterone / pharmacology*
Humans
Molecular Structure
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents
poststerone
Ecdysterone