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

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 Full article

Journal

Steroids
ISSN: 0039-128X , E-ISSN: 1878-5867

Output data

Year: 2019, Volume: 150, Article number : 108443, Pages count : DOI: 10.1016/j.steroids.2019.108443

Tags

Lupane conjugate; Oxadiazole; Amino acid; Anti-inflammatory; Keap1-IKK- docking

Authors

Popov Sergey A. ¹ , Semenova Marya D. ¹ , Baev Dmitry S. ¹ , Sorokina Irina, V ¹ , Zhukova Natalya A. ¹ , Frolova Tatyana S. ^2,3 , Tolstikova Tatyana G. ¹ , Shults Elvira E. ¹ , Turks Maris ⁴

Affiliations

1	(Данные Web of science) Novosibirsk Inst Organ Chem, Acad Lavrentyev Ave 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Fed Res Ctr Inst Cytol & Genet, Acad Lavrentyev Ave 10, Novosibirsk 630090, Russia
3	(Данные Web of science) Novosibirsk State Univ, Pirogov St 2, Novosibirsk 630090, Russia
4	(Данные Web of science) Riga Tech Univ, Fac Mat Sci & Appl Chem, Inst Technol Organ Chem, P Valdena Str 3, LV-1048 Riga, Latvia

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 to-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 NF kappa B 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.

Popov S.A. , Semenova M.D. , Baev D.S. , Sorokina I.V. , Zhukova N.A. , Frolova T.S. , Tolstikova T.G. , Shults E.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. V.150. 108443 . DOI: 10.1016/j.steroids.2019.108443 WOS Scopus РИНЦ

Published print:

Oct 1, 2019

Web of science	WOS:000486110300010
Scopus	2-s2.0-85068956584
Elibrary	41619814
OpenAlex	W2960000279