Lupane-Type Conjugates with Aminoacids, 1,3,4- Oxadiazole and 1,2,5-Oxadiazole-2-Oxide Derivatives: Synthesis, Anti-Inflammatory Activity and in Silico Evaluation of Target Affinity

Steroids 2019
Sergey A. Popov, Marya D. Semenova, Dmitry S. Baev, Irina V. Sorokina, Natalya A. Zhukova, Tatyana S. Frolova, Tatyana G. Tolstikova, Elvira E. Shults, Māris Turks

With the purpose to improve anti-inflammatory activity, the impact of introduction of 1,2,5- and 1,3,4-oxadiazole fragments to betulonic acid core as well as hybrids tethered with short ω-amino acids has been studied. The anti-inflammatory activity of synthesized compounds was tested in vivo using models of inflammation induced by concanavalin A and histamine. The majority of new compounds demonstrated higher anti-inflammatory activity compared with starting betulonic acid. To confirm the molecular targets of new derivatives in NRf2 and NFκB pathways the docking at Kelch and BTB active sites of Keap1 as well as IKK was done. The novelty of the present work is the development of new class of low toxic anti-inflammatory substances consisting of amino acid-linked betulonic acid - oxadiazole conjugates. These compounds can be considered as prospective chemopreventive agents.

Keywords
Amino acid, Anti-inflammatory, Keap1- IKK- docking, Lupane conjugate, Oxadiazole
DOI
10.1016/j.steroids.2019.108443
Hyperlink
https://www.sciencedirect.com/science/article/pii/S0039128X19301333

Popov, S., Semenova, M., Baev, D., Sorokina, I., Zhukova, N., Frolova, T., Tolstikova, T., Shults, E., Turks, M. Lupane-Type Conjugates with Aminoacids, 1,3,4- Oxadiazole and 1,2,5-Oxadiazole-2-Oxide Derivatives: Synthesis, Anti-Inflammatory Activity and in Silico Evaluation of Target Affinity. Steroids, 2019, Vol.150, Article number 108443. ISSN 0039-128X. Available from: doi:10.1016/j.steroids.2019.108443

Publication language
English (en)