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Acta Pharmaceutica, Vol. 67 No. 4, 2017.

Original scientific paper

https://doi.org/10.1515/acph-2017-0032

A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle cells with xyloketals from marine fungi

JIE-BIN ZHOU ; Department of Guangdong Key Laboratory for New Pharmaceutical Dosage Forms, GuangDong Pharmaceutical University, Guangzhou, 510006, P. R. China
YING-YING SUN ; School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, P. R. China
YING-LIN ZHENG ; School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, P. R. China
CHU-QIN YU ; Department of Guangdong Key Laboratory for New Pharmaceutical Dosage Forms, GuangDong Pharmaceutical University, Guangzhou, 510006, P. R. China
HUA-QING LIN ; Department of Guangdong Key Laboratory for New Pharmaceutical Dosage Forms, GuangDong Pharmaceutical University, Guangzhou, 510006, P. R. China
JI-YAN PANG ; School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, P. R. China

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Abstract

In this study, the effect of four xyloketal compounds 1-4 on store-operated calcium entry (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual ketal compound with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals were easily penetrable through the cell membrane. Moreover, the molecular docking study of xyloketal A with activation region of the stromal interaction molecule (STIM) 1 and the calcium release-activated calcium modulator (ORAI) 1 (STIM1-ORAI1) protein complex, the key domain of SOCE, revealed that xyloketal A exibited non-covalent interaction with the key residue lysine 363 (LYS363) in the identified cytosolic regions in STIM1-C. These findings provided useful information for xyloketal A as SOCE inhibitor for further evaluation.

Keywords

xyloketal A; store-operated calcium entry; molecular docking; IL-8; parallel artificial membrane permeability assay

Hrčak ID:

186324

URI

https://hrcak.srce.hr/186324

Publication date:

31.12.2017.

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