[In vitro and in silico Determination of the Interaction of Artemisinin with Human Serum Albumin]

Artemisinins are secondary metabolites of the medicinal plant Artemisia annua, have anti-inflammatory, anticarcinogenic, immunomodulating, antimicrobial and other properties. However, the pharmacokinetics, pharmacodynamics, exact molecular targets of artemisinin are not well known. The interaction of artemisinin with human serum albumin was studied both in vitro and in silico, and compared with dexamethasone. The quenching of the fluorescence emission of human serum albumin with artemisinin at different temperatures proceeded according to a single mechanism and indicated the static nature, which is similar to the effect of dexamethasone. Artemisinin and dexamethasone interact with Drug site I on human serum albumin. We have shown for the first time the formation of hydrogen bond with Arg218, which plays a crucial role in the binding of drugs at site I. Dexamethasone forms hydrogen bonds with the side chain of Arg218 and Arg222 and the main chain of Val343. The amino acids of subdomains IIA and IIIA of human serum albumin coincide for both compounds. Studies of the electrophoretic mobility of DNA of sarcoma S-180 cells show that artemisinin does not interact directly with DNA. Therefore, we assume that one of the main transporters of artemisinin is human serum albumin. Moreover, the interaction parameters of artemisinin with human serum albumin coincide with those of dexamethasone.

Keywords: artemisinin; dexamethasone; electrophoretic mobility; fluorescence; human serum albumin; molecular dynamics.