# Phosphoramidate Derivatives of Betulin, New Molecules with Promising Biological Activity: Synthesis and Characterization

## TL;DR

This study creates and tests new betulin derivatives with promising anti-cancer properties, particularly compound 7A, which shows strong apoptosis-inducing effects.

## Contribution

The paper introduces new phosphoramidate betulin derivatives and identifies compound 7A as a highly effective anti-cancer molecule.

## Key findings

- Compound 7A showed the strongest effect on apoptosis and caspase 3/7 activation.
- Compound 7A exhibited high lipophilicity, which may enhance its biological activity.
- The new derivatives were synthesized using the Staudinger, Steglich, and Jones reactions.

## Abstract

Studies of natural products and their semisynthetic derivatives are a valuable source of therapeutic agents. The aim of this work was to obtain new 30-phosphoramidate derivatives of betulin and determine their biological potential. The synthetic approach utilized the Staudinger reaction (the introduction of a phosphoramidate group), the Steglich reaction (the introduction of an alkynyl group), and the Jones reaction (the introduction of a carboxyl group). The structures of the target compounds were determined using spectroscopic methods (1H NMR, 13C NMR, 31P NMR, and HRMS). The new derivatives were tested for antiproliferative activity against MV4-11, A549, MCF-7, PC-3, and HCT116 cancer cells and against normal MCF-10A cells using the MTT and SRB methods. Apoptosis studies were performed for the most active compounds (6B and 7A), potential molecular targets (AutoDock software) were identified, and lipophilicity parameters (RP-TLC method, SwissADME website) were determined. The greatest effect on apoptosis and caspase 3/7 activation was observed for the diester derivative 7A. Compound 7A showed a high lipophilicity parameter in the study group.