519
Volume 5, Issue 10: Special Issue
(EJAR)
ISSN: 2181-2020
MPHAPP
THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL
CONFERENCE
“
MODERN PHARMACEUTICS: ACTUAL
PROBLEMS AND PROSPECTS
”
TASHKENT, OCTOBER 17, 2025
in-academy.uz
INVESTIGATION OF THE CYTOTOXICITY OF NEW AMIODARONE
DERIVATIVES IN NORMAL HEPATOCYTE CULTURE
Khashimova Z.S.
Salakhutdinova M.K.
Kakhorova K.A.
Uzbekov V.V.,
Oshchepkova Yu.I.
Salikhov Sh.I.
e-mail: malika.salahutdinova@mail.ru
Republic of Uzbekistan, Tashkent 100125, 83 Mirzo Ulugbek Street, A.S. Sadykov Institute of
Bioorganic Chemistry, Academy of Sciences of the Republic of Uzbekistan
https://doi.org/10.5281/zenodo.17343802
Arrhythmias remain a pressing challenge in modern cardiology because of their high prevalence
and the serious threat they pose to patient survival. Current antiarrhythmic drugs, although effective,
are often associated with side effects involving the central nervous system, the gastrointestinal tract,
and other organ systems.
Amiodarone (Cordarone), one of the most widely used drugs in clinical practice, is particularly
well known for its systemic toxicity. Its most severe adverse effect is pulmonary injury, but it also
has toxic effects on the thyroid gland and the liver. These can range from asymptomatic increases in
transaminase activity to severe liver failure requiring transplantation. Such limitations highlight the
need to develop new forms of amiodarone with improved solubility and reduced toxicity.
In earlier work, we developed supramolecular complexes of amiodarone with glycyrrhizic acid
(GA) and with its monoammonium salt (MGA) at molar ratios of 1:2, 1:4, and 1:8. A comparative
study on HeLa cells demonstrated that these modified forms had significantly lower toxicity
compared with the native drug [1].
The present study was designed to evaluate the cytotoxicity of these complexes in a
transplantable line of normal hepatocytes (Hep23).
Hep23 cells were cultured in RPMI-1640 medium in a CO₂ incubator, exposed to the test
compounds, and then incubated again under the same conditions. Cytotoxicity was assessed using the
MTT assay, a method that measures cellular metabolic activity and viability [2]. Untreated cells
(defined as 100% viability) and the antitumor drug cisplatin were used as controls.
The experiments showed that the original amiodarone was highly toxic to hepatocytes at a
concentration of 100 μg/mL; only 4.6% of cells survived. In contrast, amiodarone-GA complexes
displayed markedly lower toxicity. At a 1:2 molar ratio, the toxicity was 20.31%; at 1:8, it fell to
5.44%. At a 1:4 ratio, no toxic effect was detected, and cell viability was essentially identical to the
control (101.88%).
Amiodarone–MGA complexes showed no significant cytotoxicity at any of the molar ratios
tested (1:2, 1:4, or 1:8). Cell viability remained in the range of 97–135%, with the strongest
proliferative effect observed at the 1:4 ratio, similar to the GA complexes.
In summary, modified forms of amiodarone based on GA and MGA demonstrated substantially
reduced toxicity toward healthy hepatocytes compared with the parent drug. These findings are
consistent with our earlier results in the HeLa tumour cell line and further support the protective role
of these ligands.
