Photostability and Antiproliferative Activity of Furan Analogues of Combretastatin A-4.

Autor: Scherbakov A; N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye sh. 24, 115522 Moscow, Russian Federation., Zakharov AV; N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russian Federation., Mikhaevich EI; N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye sh. 24, 115522 Moscow, Russian Federation., Salnikova DI; N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye sh. 24, 115522 Moscow, Russian Federation., Yadykov AV; N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russian Federation., Kozhevnikova AA; N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russian Federation., Shirinian VZ; N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russian Federation.
Jazyk: angličtina
Zdroj: Chemical research in toxicology [Chem Res Toxicol] 2022 Nov 21; Vol. 35 (11), pp. 2014-2024. Date of Electronic Publication: 2022 Sep 09.
DOI: 10.1021/acs.chemrestox.2c00204
Abstrakt: Cancer is one of the most serious health problems that usually require heavy medical treatment. It is important to ensure that no additional burden is placed on patients due to the modes of administration and/or poor quality of pharmaceuticals. In this regard, understanding, quantifying, and improving the photostability (resistance to UV light or sunlight) of drugs is among the important elements that can improve the patient's quality of life. In this work, the photochemical properties of a wide range of furanone analogues of combretastatin A-4 and their antiproliferative activity against A-431 epidermoid carcinoma cells were studied in a search for compounds with improved photostability and antiproliferative activity. It was found that the incorporation of an arylidene moiety led to a significant improvement in photostability, while the antiproliferative activity strongly depends on the nature of the aryl residue in the arylidene moiety. The high photostability of arylidenes was achieved due to the delocalization of the central double bond of the 1,3,5-hexatriene system, which limited the 6π-electrocyclization. The best results in terms of antiproliferative activity were obtained for thiophene arylidene (IC 50 = 0.6 μM) and 3,4-diarylfuran (IC 50 = 0.047 μM). The obtained results address the lack of data available now in scientific literature on the photodegradation of combretastatin A-4 analogues and should be taken into account in studies of the side effects of pharmaceuticals based on them.
Databáze: MEDLINE