Synthesis and biological evaluation of new derivatives of grossheimin


Adekenov S.М. Shaimerdenova Z.R. Adekenova K.S. Kishkentayeva A.S.
April 2022Elsevier B.V.

Fitoterapia
2022#158

Grossheimin 1 is a polyfunctionalized sesquiterpene, featuring, in addition to the exomethylene-γ-lactone group, also an additional exocyclic double bond, a hydroxyl, and a ketone carbonyl. These functional groups have been modified, generally in an orthogonal way, by arylation of the exomethylene, by the introduction of heteroatoms associated to oxygen-, nitrogen- and phosphorous functionalities, and by acylation. A selection of the analogues was investigated for bioactivity, showing that the introduction of a substituent at C-13 is not detrimental, and can modulate potency independently from retention or reduction of the C-11 – C-13 exomethylene double bond and the effect of this maneuver on Michael reactivity. In vivo experiments of 26 samples made it possible to establish that grossheimin 1 and its five new derivatives have a pronounced antitumor activity against alveolar liver cancer, Pliss lymphosarcoma, Walkers carcinosarcoma, sarcoma 45, M-1 sarcoma, P-388 leukemia.

Biological activity , Grossheimin , New derivatives , Sesquiterpene lactone , Synthesis

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JSC “International Research and Production Holding “Phytochemistry”, Karaganda, 100009, Kazakhstan
Nazarbayev University, Center for life sciences, Nur-Sultan, 010000, Kazakhstan

JSC “International Research and Production Holding “Phytochemistry”
Nazarbayev University

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