# Antiproliferative and Trypanocidal Activity of Ivermectin Bioconjugates

## TL;DR

Researchers synthesized new ivermectin-based compounds that show improved antiparasitic and anticancer effects.

## Contribution

The study introduces ten new ivermectin bioconjugates with enhanced biological activity and selectivity.

## Key findings

- Many ivermectin conjugates showed higher activity than their parent compounds.
- Compound 16, an ivermectin-artesunate conjugate, was significantly more active and non-toxic to reference cells.
- The conjugates demonstrated effectiveness against Trypanosoma brucei brucei and various cancer cell lines.

## Abstract

Ivermectin (IVR), whose discovery has been
Nobel-Prize-honored,
is a 16-membered macrocyclic lactone used in medicine as an extremely
effective and safe antiparasitic drug. In recent years, interest in
this compound has grown due to its potential effectiveness in killing
various types of cancer cells. However, research on the anticancer
activity of IVR derivatives is limited. Additionally,
the growing problem of drug resistance raises concerns about the effectiveness
of this drug in the treatment of parasitic diseases. Therefore, in
this work, we provide a detailed description of the synthesis of ten
new IVR bioconjugates with compounds exhibiting high
anticancer and/or antimicrobial activity. We also assess the effectiveness
of these hybrids in killing Trypanosoma brucei brucei a protozoan parasite that causes African trypanosomiasis, as well
as their anticancer activity toward various cancer cell lines. Many
of the newly synthesized conjugates exhibited higher biological activity
than their respective parent compounds as well as increased selectivity
indices. The IVR conjugate with artesunate (compound 16) appears particularly interesting, as it proved not only
to be several times more active than the parent compounds but also
showed no toxicity toward a reference cell line, indicating its potential
as a therapeutic agent.