Abstract
A new antitumor multi-target drug anthrafuran, with cellular targets such as topoisomerase I/II and some protein kinases, was obtained in Gause Institute of New Antibiotics and was demonstrated to have a reliable specific effect on different murine and human tumor models by oral administration. In this study, we focused on the evaluation of subchronic toxicity of oral anthrafuran drug formulation (AF) on Chinchilla rabbits. The absence of any changes in the condition or behavior of animals was shown for oral anthrafuran. Changes with reversible and dose-dependent hepato- and nephrotoxicity at low doses, as well as hemato- and gastrointestinal toxicity at high doses, were confirmed pathomorphologically. The identified toxic properties are extremely valuable, since oral anthrafuran does not have the limiting cardio- and myelotoxicity. Anthrafuran with 2 mg/kg/day or 6 mg/kg/day doses was administrated orally over 15 days. Investigations include assessment of the body weight, hematological and serum biochemical parameters and urinalysis, electrocardiography and pathomorphological evaluation of the internal organs. Quantitative data were processed statistically with Student’s t-Test, p < 0.05. Revealed during the subchronic study were the favorable toxicological properties of oral anthrafuran as opposed to clinical anthracyclines, oral idarubicin, or parenteral doxorubicin, which allows it to be considered promising for further research.
Highlights
Heteroarenanthracenediones containing cyclic diamines in the side chain are known to have high antiproliferative activity [1,2,3,4,5]
A study of the kinetics of dissolution of anthrafuran substance in bio-relevant media showed that anthrafuran refers to preparations with a low biopharmaceutical solubility
(1/15 maximum tolerated dose dose (MTD)) and 6 mg/kg/day (1/15 LD50 )—followed by a 15-day observation period, has a more favorable toxicological profile compared to doxorubicin and other anthracyallowed us to identify all of the main toxic effects of anthrafuran
Summary
Heteroarenanthracenediones containing cyclic diamines in the side chain are known to have high antiproliferative activity [1,2,3,4,5]. Novel orally administrated agents have a well-delivered formulation to achieve adequate bioavailability High bioavailability makes it possible to achieve complete or partial remission with oral administration of certain alkylating agents, antitumor antibiotics, and other classes of anticancer drugs. In this regard, more and more oncologists have begun to give preference. Pharmaceuticals 2021, 14, 900 other classes of anticancer drugs In this regard, more and more oncologists have begun to give preference to oral chemotherapy drugs, since this route of administration imto oral chemotherapy drugs, since this route of administration improves the quality of proves the quality of life of patients and reduces their time in the clinic [10].
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