Planta Med 2019; 85(18): 1522
DOI: 10.1055/s-0039-3400016
Main Congress Poster
Poster Session 2
© Georg Thieme Verlag KG Stuttgart · New York

Inhibition of heat shock protein 90 (Hsp90) by diterpenoids from roots of Zhumeria majdae

R Zadali
1   Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences,, Tehran, Iran
,
A Hadjiakhoondi
1   Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences,, Tehran, Iran
,
M D’Ambola
2   Dipartimento di Farmacia, Universitàdi Salerno,, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy
,
L Fiengo
2   Dipartimento di Farmacia, Universitàdi Salerno,, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy
,
N de Tommasi
2   Dipartimento di Farmacia, Universitàdi Salerno,, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy
,
S Nejad-Ebrahimi
2   Dipartimento di Farmacia, Universitàdi Salerno,, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy
3   Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University,, Tehran, Iran
› Author Affiliations
Further Information

Publication History

Publication Date:
20 December 2019 (online)

 

Zhumeria majdae Rech.f. & Wendelbo is an endemic plant in Iran. and an unique member of Zhumeria genus. The constituents of this genus are rarely studied. Roots of Z. majdae were extracted with n-hexane, ethyl acetate, and methanol, respectively. The phytochemical investigation of the n-hexane extract by different chromatographic techniques, such as Silica gel and Sephadex LH-20 chromatography, and RP-HPLC, led to the isolation and identification of two new abietane diterpenes, 1-hydroxysahandone and 1-hydroxy-11-demethylsahandone, and 18 known abietane derivatives [1], [2]. The structures of the isolated compounds were elucidated by 1D and 2D NMR and MS techniques and absolute configurations were established by circular dichroism spectroscopy. A surface plasmon resonance analysis (SPR), MTT assay (Hela & MCF 7 cancer cell lines) western blot (WB) analysis on HSP-90 and several of its client proteins, including HSP-70, p-Akt, Akt, Cyclin A, p-Erk1 and Erk1, along with ATPase activity were implemented to screen a small diterpene library towards HSP90. This chaperone is involved in the turnover, trafficking, and folding of a large number of proteins, including oncoproteins. Thus, there is an interest in the development of new anticancer drugs targeting HSP90 [3]. Results showed that among all isolated diterpenes, lanugon Q showed higher affinity towards HSP90, with SPR KD of 2.98±1.97 nM. The results of WB and MTT assays were in agreement with SPR analysis. However, in the ATPase assay, lanugon Q did not show any inhibition.

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Fig. 1
 
  • References

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