Identification of Key Structural Characteristics of Schisandra
chinensis Lignans Involved in P-Glycoprotein Inhibition

J 2014

Identification of Key Structural Characteristics of Schisandra chinensis Lignans Involved in P-Glycoprotein Inhibition

SLANINA, Jiří; Gabriela PÁCHNIKOVÁ; Martina ČARNECKÁ; Ludmila KOUBÍKOVÁ; Lenka ADÁMKOVÁ et al.

Základní údaje

Originální název

Identification of Key Structural Characteristics of Schisandra chinensis Lignans Involved in P-Glycoprotein Inhibition

Autoři

SLANINA, Jiří; Gabriela PÁCHNIKOVÁ; Martina ČARNECKÁ; Ludmila KOUBÍKOVÁ; Lenka ADÁMKOVÁ; Otakar HUMPA; Karel ŠMEJKAL a Iva SLANINOVÁ

Vydání

Journal of Natural Products, Washington, American Chemical Society, 2014, 0163-3864

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.798

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/14:00077244

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

RESISTANCE-ASSOCIATED PROTEIN-1; MEDIATED MULTIDRUG-RESISTANCE; CANCER-CELLS; DIBENZOCYCLOOCTADIENE LIGNANS; ABSOLUTE STRUCTURE; DRUG-RESISTANCE; GOMISIN-N; CONSTITUENTS; BAILL; SCHIZANDRIN

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 1. 2015 14:29, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

The aim of the present study was to determine the structural requirements for dibenzocyclooctadiene lignans essential for P-glycoprotein inhibition. Altogether 15 structurally related lignans isolated from Schisandra chinensis or prepared by modification of their backbone were investigated, including three pairs of enantiomers. P-Glycoprotein inhibition was quantified using a doxorubicin accumulation assay in human promyelotic leukemia HL60/MDR cells overexpressing P-glycoprotein. A preliminary quantitative structure-activity relationship analysis revealed three main structural features involved in P-glycoprotein inhibition: a 1,2,3-trimethoxy moiety, a 6-acyloxy group, and the absence of a 7-hydroxy group. The most effective inhibitors, (-)-gomisin N (1) and (+)-deoxyschizandrin [(+)-2], were selected for further evaluation of their effects. Both these lignans restored the cytotoxic effect of doxorubicin in HL60/MDR cells and when combined with a subtoxic concentration of this compound increased the proportion of G2/M cells significantly, which is a usual response to treatment with this anticancer drug.

Návaznosti

MUNI/A/0938/2013, interní kód MU

Název: Biomedicína na molekulární a buněčné úrovni (Akronym: BMBÚ)

Investor: Masarykova univerzita, Biomedicína na molekulární a buněčné úrovni, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

MUNI/A/0954/2013, interní kód MU

Název: Příspěvek chemických a biochemických metodik ke studiu molekulární podstaty vybraných patologických stavů a onemocnění (Akronym: BIOMET3)

Investor: Masarykova univerzita, Příspěvek chemických a biochemických metodik ke studiu molekulární podstaty vybraných patologických stavů a onemocnění, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Přiložené soubory

EL_Identification_of_Key.pdf

Požádat o autorskou verzi souboru

Citovat

SLANINA, Jiří; Gabriela PÁCHNIKOVÁ; Martina ČARNECKÁ; Ludmila KOUBÍKOVÁ; Lenka ADÁMKOVÁ; Otakar HUMPA; Karel ŠMEJKAL a Iva SLANINOVÁ. Identification of Key Structural Characteristics of Schisandra chinensis Lignans Involved in P-Glycoprotein Inhibition. Journal of Natural Products. Washington: American Chemical Society, 2014, roč. 77, č. 10, s. 2255-2263. ISSN 0163-3864. Dostupné z: https://doi.org/10.1021/np500521v.

@article{1205567,
   author = {Slanina, Jiří and Páchniková, Gabriela and Čarnecká, Martina and Koubíková, Ludmila and Adámková, Lenka and Humpa, Otakar and Šmejkal, Karel and Slaninová, Iva},
   article_location = {Washington},
   article_number = {10},
   doi = {https://doi.org/10.1021/np500521v},
   keywords = {RESISTANCE-ASSOCIATED PROTEIN-1; MEDIATED MULTIDRUG-RESISTANCE; CANCER-CELLS; DIBENZOCYCLOOCTADIENE LIGNANS; ABSOLUTE STRUCTURE; DRUG-RESISTANCE; GOMISIN-N; CONSTITUENTS; BAILL; SCHIZANDRIN},
   language = {eng},
   issn = {0163-3864},
   journal = {Journal of Natural Products},
   title = {Identification of Key Structural Characteristics of Schisandra chinensis Lignans Involved in P-Glycoprotein Inhibition},
   volume = {77},
   year = {2014}
}

TY  - JOUR
ID  - 1205567
AU  - Slanina, Jiří - Páchniková, Gabriela - Čarnecká, Martina - Koubíková, Ludmila - Adámková, Lenka - Humpa, Otakar - Šmejkal, Karel - Slaninová, Iva
PY  - 2014
TI  - Identification of Key Structural Characteristics of Schisandra chinensis Lignans Involved in P-Glycoprotein Inhibition
JF  - Journal of Natural Products
VL  - 77
IS  - 10
SP  - 2255-2263
EP  - 2255-2263
PB  - American Chemical Society
SN  - 01633864
KW  - RESISTANCE-ASSOCIATED PROTEIN-1
KW  - MEDIATED MULTIDRUG-RESISTANCE
KW  - CANCER-CELLS
KW  - DIBENZOCYCLOOCTADIENE LIGNANS
KW  - ABSOLUTE STRUCTURE
KW  - DRUG-RESISTANCE
KW  - GOMISIN-N
KW  - CONSTITUENTS
KW  - BAILL
KW  - SCHIZANDRIN
N2  - The aim of the present study was to determine the structural requirements for dibenzocyclooctadiene lignans essential for P-glycoprotein inhibition. Altogether 15 structurally related lignans isolated from Schisandra chinensis or prepared by modification of their backbone were investigated, including three pairs of enantiomers. P-Glycoprotein inhibition was quantified using a doxorubicin accumulation assay in human promyelotic leukemia HL60/MDR cells overexpressing P-glycoprotein. A preliminary quantitative structure-activity relationship analysis revealed three main structural features involved in P-glycoprotein inhibition: a 1,2,3-trimethoxy moiety, a 6-acyloxy group, and the absence of a 7-hydroxy group. The most effective inhibitors, (-)-gomisin N (1) and (+)-deoxyschizandrin [(+)-2], were selected for further evaluation of their effects. Both these lignans restored the cytotoxic effect of doxorubicin in HL60/MDR cells and when combined with a subtoxic concentration of this compound increased the proportion of G2/M cells significantly, which is a usual response to treatment with this anticancer drug.
ER  -

SLANINA, Jiří; Gabriela PÁCHNIKOVÁ; Martina ČARNECKÁ; Ludmila KOUBÍKOVÁ; Lenka ADÁMKOVÁ; Otakar HUMPA; Karel ŠMEJKAL a Iva SLANINOVÁ. Identification of Key Structural Characteristics of Schisandra chinensis Lignans Involved in P-Glycoprotein Inhibition. \textit{Journal of Natural Products}. Washington: American Chemical Society, 2014, roč.~77, č.~10, s.~2255-2263. ISSN~0163-3864. Dostupné z: https://doi.org/10.1021/np500521v.

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