Synthesis of furanotriterpenoids from betulin and evaluation of Tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitory properties of new semi-synthetic triterpenoids.

For the first time, a synthetic route for preparing lupane and oleanane derivatives with a hydrogenated furan ring as a cycle A of triterpene scaffold is described. Most of the synthesized compounds, furanoterpenoids and their synthetic intermediates, were non-toxic against the tested cancer and non-cancerous cell lines, and evinced significant inhibitory activity with IC 1.0-9.

Synthesis and Anticancer Activity of A-Ring-Modified Derivatives of Dihydrobetulin.

Multidrug resistance (MDR) is a common phenomenon in clinical oncology, whereby cancer cells become resistant to chemotherapeutic drugs A common MDR mechanism is the overexpression of ATP-binding cassette efflux transporters in cancer cells, with P-glycoprotein (P-gp) being one of them. New 3,4-seco-lupane triterpenoids, and the products of their intramolecular cyclization with the removed 4,4-gem-dimethyl group, were synthesized by the selective transformations of the A-ring of dihydrobetulin. Among the semi-synthetic derivatives, the MT-assay-enabled methyl ketone (), exhibiting the highest cytotoxicity (0.

The Molecular Mechanisms of Oleanane Aldehyde-β-enone Cytotoxicity against Doxorubicin-Resistant Cancer Cells.

Oleanane aldehyde-β-enone (), being the semi-synthetic derivative of the triterpenoid betulin, effectively inhibits the proliferation of HBL-100 and K562 cancer cells (IC 0.47-0.53 µM), as well as the proliferation of their resistant subclones with high P-gp expression HBL-100/Dox, K562/i-S9 and K562/i-S9_Dox (IC 0.

Synthesis, cytotoxic evaluation, and molecular docking studies of the semi-synthetic "triterpenoid-steroid" hybrids.

Synthetic transformations of steroids for drug discovery and improvement of drug effectiveness have been an important part of modern medicinal chemistry and pharmaceutical sciences. Pentacyclic triterpenoids, being represented in the nature by various structures and biogenetically related to steroids, can largely expand the spectrum of biologically active steroidal agents via synthesis of the so-called "triterpenoid-steroid" hybrids. In the presented work, the nitrile anion cyclizations of 3,4-secolupane and 3,4-seco-oleanane nitriles and follow-up synthetic transformations of the cyclized products with formation of the gemm-dimethyl-free A ring "triterpenoid-steroid" hybrids were studied.

Synthesis of cytotoxically active derivatives based on alkylated 2,3-seco-triterpenoids.

Extremely low content of biologically active triterpenoids with the fragmented or contracted ring A extractable from plants is the main disadvantage of their use in drug discovery and practical pharmacology. Development of new methods for synthesis of these compounds and their structural analogs from bioavailable triterpene precursors gives an opportunity to obtain promising agents for pharmacology with excellent yields. A new approach to synthesis of alkylated A-seco-triterpenoids, including the Beckmann fragmentation of 3-methyl-substituted allobetulin or betulinic acid methyl ester with 2-hydroxyimino group in the ring A was proposed.