Naslov
Anthraquinones as potential free radical scavengers and P-glycoprotein inhibitors

Autori
Jeremić, Svetlana ; Amić, Ana ; Stanojević-Pirković, Marijana ; Marković, Zoran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of abstracts JMMC 2019 – Joint Meeting on Medicinal Chemistry 2019 / - Prag : GUARANT International spol. s r.o., 2019, 31-31

ISBN
978-80-907442-0-2

Skup
11th Joint Meeting on Medicinal Chemistry 2019

Mjesto i datum
Prag, Češka Republika, 27.06.2019. - 30.06.2019

Vrsta sudjelovanja
Plenarno

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
scavenging ; DFT ; solvent polarity ; docking ; P-glycoprotein

Sažetak
Increase in the amount of free radicals formed during metabolic processes leads to a phenomenon known as oxidative stress and can cause various diseases such as cardiovascular diseases, carcinogenesis, aging-associated diseases, etc. The role of antioxidants is to remove excess free radicals and to terminate their harmful effect on cells. We investigated free radical scavenging capacity of six structurally similar anthraquinones (alizarin, purpurin, chrysophanol, emodin, aloe-emodin and 1, 3, 8-trihydroxyanthraquinone) for inactivation of ten selected free radicals. The antioxidant capacity was estimated by considering Gibbs free energy of three studied reaction mechanisms: hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). Calculations were performed by using M06-2X/6-311++G(d, p) level of theory, as implemented in the Gaussian program package. Obtained results indicate HAT and SPLET as operative and competitive, while SET-PT is not thermodynamically plausible. Among studied anthraquinones, alizarin and purpurin showed the highest scavenging capacity. One of the most important proteins, which enables detoxification of cells, is P- glycoprotein (Pgp). It operates by exporting numerous unrelated toxins out of the cell, ensuring cell protection. Despite the invaluable role of Pgp in cell protection, significant disadvantage of this enzyme is its poor selectivity. Various studies confirm Pgp’s low substrate selectivity as the cause of the phenomena known as multiple drug resistance (MDR), therefore we investigated inhibition activity of selected anthraquinones towards Pgp. Pgp structure was assumed from Protein Data Bank. Docking analysis was performed at the whole molecule, with the aim to investigate two-chain boundary positions as potential docking sites. Using the AutoDock 4.2 program package, docking positions of the most stable anions to the Pgp were estimated. To calculate Kollman charges and to add polar hydrogens, the AutoDockTools (ADT) graphical user interface was applied. Flexibility of the ligand was considered, while the protein remained a rigid structure in the ADT. The Geistenger method for calculation of partial charges was employed. All calculations for protein–ligand flexible docking were carried out using the Lamarckian Genetic Algorithm method. Obtained results suggest that all investigated compounds are potential inhibitors of Pgp under physiological conditions, indicating them as potential protectors against patient resistance toward various anticancer drugs.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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