N-Alkylation of Anthracycline Antibiotics by Natural Sesquiterpene Lactones as a Way to Obtain Antitumor Agents with Reduced Side Effects

Abstract

Anthracycline antitumor antibiotics are one of the promising classes of chemotherapeutic agents for cancer treatment. The main deterrent to their use is high toxicity to a healthy environment, including cumulative cardiotoxicity. In our work, bipharmacophore molecules containing in their structure a fragment of the known anthracycline antibiotics daunorubicin and doxorubicin and natural sesquiterpene lactones were obtained for the first time. When studying the biological activity of the synthesized compounds, it was found that with equal and, in some cases, higher cytotoxicity and glycolysis inhibition by anthracycline antibiotics conjugates with sesquiterpene lactones in comparison with doxo- and daunorubicin, a reduced damaging effect on the functioning of rat heart mitochondria was observed. The results obtained allow us to confirm the assumption that the chemical modification of the anthracycline antibiotics molecules doxo- and daunorubicin by natural sesquiterpene lactones can be a promising strategy for creating potential antitumor chemotherapeutic drugs with a pronounced cytotoxic effect on tumor cells and a reduced damaging effect on healthy cells of the human organism.

Optimal synthesis conditions for NBF-modified 8,13-dihydroberberine derivatives

“…The impact of the compounds on the process of lipid peroxidation was evaluated using the Thiobarbituric Acid Reactive Substances (TBARS) test with modifications for a plate format. 98…”

“…The impact of the compounds on the process of lipid peroxidation was evaluated using the Thiobarbituric Acid Reactive Substances (TBARS) test with modifications for a plate format. 98 The mitochondrial membrane potential of rat liver mitochondria was measured using a plate reader analyzer, Victor 3 (PerkinElmer, USA), with the voltage-sensitive indicator safranin A. 98 The mitochondrial suspension contained 0.5 mg of protein in 1 mL of buffer.…”

“…98 The mitochondrial membrane potential of rat liver mitochondria was measured using a plate reader analyzer, Victor 3 (PerkinElmer, USA), with the voltage-sensitive indicator safranin A. 98 The mitochondrial suspension contained 0.5 mg of protein in 1 mL of buffer. The mitochondrial membrane energization was performed using 5 mM potassium succinate in the presence of 1 mM rotenone, and the maximum depolarization was induced by adding 25 mM CaCl 2 .…”

Design of Conjugates Based on Sesquiterpene Lactones with Polyalkoxybenzenes by “Click” Chemistry to Create Potential Anticancer Agents

“…Cell viability was determined by MTT test as described earlier [ 54 ]. Cells were seeded in a 96-well plate in the amount of 1 × 10 4 cells/200 µL and cultured at 37 °C in a humidified CO 2 atmosphere (5%) in a nutrient medium DMEM (PanEco, Moscow, Russia) and MEM (PanEco, Moscow, Russia).…”

Glucosamine conjugated iron oxide and graphene oxide nanohybrid for smart drug delivery

“…As a result of damage to the cells of myocardium membranes induced by the persistent ingestion of drugs of this class, cardiomyopathy, and treatment‐resistant congestive heart failure occur. [ 33 ] To reduce the side effects of DNR, in this study, a hybrid of GO and Fe 3 O 4 nanoparticles (Fe 3 O 4 @GO), as a promising candidate for drug delivery systems, was successfully synthesized via the co‐precipitation method, which was also investigated as a targeting agent. This novel modified Fe 3 O 4 @GO‐GA nanocomposite demonstrated good potential for the efficient transfer of anticancer drugs to tumour cells.…”