Objective:To investigate the molecular effects ofNerium oleanderleaf distillate on paclitaxel and vincristine resistant(MCF-7/Pac and MCF-7/Vinc)cells and sensitive(MCF-7/S)cell lines.Methods:Nerium oleander(N.oleande...Objective:To investigate the molecular effects ofNerium oleanderleaf distillate on paclitaxel and vincristine resistant(MCF-7/Pac and MCF-7/Vinc)cells and sensitive(MCF-7/S)cell lines.Methods:Nerium oleander(N.oleander)leaf extract was obtained by hydrodistillation method.The toxicological effects ofN.oleanderdistillate,previously suggested as medicinal food supplement,on drug resistant cells were evaluated by XTT tests.MDR modulation potential of the plant material was evaluated by flow cytometry and fluorescent microscopy.Paclitaxel and vincristine were applied to the sublines in combination with N.oleanderdistillate.Results:Fractional inhibitory indices show thatN.oleanderdistillate did not increase the antiproliferative effects of anticancer drugs.N.oleandertreatment in to MCF-7/Pac and MCF-7/Vinc did not inhibit P-gp activity and MDR1 gene expression level.Conclusions:As a result it may be suggested that althoughN.oleanderdistillate has some medicinal effects as food supplement it may not be suitable as an MDR modulator for drug resistant breast cancer cells.展开更多
Eleven biogenetically related polyprenylated acylphloroglucinols(PPAPs),including four novel skeletons(1-4)and five new com-pounds(5-9),were isolated from the flowers of Hypericum monogynum.Hypermonones A-D(1-4)repres...Eleven biogenetically related polyprenylated acylphloroglucinols(PPAPs),including four novel skeletons(1-4)and five new com-pounds(5-9),were isolated from the flowers of Hypericum monogynum.Hypermonones A-D(1-4)represented the first example of a unique dilactone structure containing carbonyl bonded single 5-lactone and tricyclic γ-lactone moieties.Their structures were elucidated by NMR analysis,X-ray crystallography,and ECD calculations.Moreover,we revised the structure of hyperibrin B to hy perm on one I(9)via NMR an alysis,a qua ntum computational chemistry method,and hypothetic bios yn thetic con siderations.Three compounds(5,6,and 9)with significant MDR reversal activity(RF ranging from 61 to 223)were superior to the positive control verapamil(MCF-7/ADR,RF:53;HepG2/ADRz RF:124).Mechanism study for compound 5 indicated that this compound could inhibit the function of P-gp tran sport rather tha n its expressi on,and the possible recog nition mechanism betwee n compo und 5 and P-gp was predicted by molecular docking.展开更多
A novel class of molecules with structure N-（3-arylpropyl）-9,10-dihydro-9-oxoacridine-4-carboxamides （20- 29） were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design so...A novel class of molecules with structure N-（3-arylpropyl）-9,10-dihydro-9-oxoacridine-4-carboxamides （20- 29） were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design software. The designed molecules were synthesized by a novel synthesis route and evaluated for their inhibitory effects on the transport activity of P-glycoprotein （P-gp） by standard Hoechst 33342 assay method. Based on the pIC50 values of ten title compounds screened, three compounds exhibited better activity as compared to Verapamil used as standard.展开更多
基金Supported by TUBITAK with the project number 111S039by the Selcuk University Research Fund with the project number 11401014
文摘Objective:To investigate the molecular effects ofNerium oleanderleaf distillate on paclitaxel and vincristine resistant(MCF-7/Pac and MCF-7/Vinc)cells and sensitive(MCF-7/S)cell lines.Methods:Nerium oleander(N.oleander)leaf extract was obtained by hydrodistillation method.The toxicological effects ofN.oleanderdistillate,previously suggested as medicinal food supplement,on drug resistant cells were evaluated by XTT tests.MDR modulation potential of the plant material was evaluated by flow cytometry and fluorescent microscopy.Paclitaxel and vincristine were applied to the sublines in combination with N.oleanderdistillate.Results:Fractional inhibitory indices show thatN.oleanderdistillate did not increase the antiproliferative effects of anticancer drugs.N.oleandertreatment in to MCF-7/Pac and MCF-7/Vinc did not inhibit P-gp activity and MDR1 gene expression level.Conclusions:As a result it may be suggested that althoughN.oleanderdistillate has some medicinal effects as food supplement it may not be suitable as an MDR modulator for drug resistant breast cancer cells.
基金supported by the National Natural Science Foundation of China(Nos.U1812403,81872772,and 81960546)the Scie nee and Tech no logy Departme nt of Guizhou Province(Nos.QKH 2020-1Z076,QKHZC[2020]4Y203z QKHJC[2018]1409,QKHZC[2019]2762,and QKHPTRC[2020]5008)+3 种基金the High-level Innovative Talents in Guizhou Provinee(Thousand Levels of Talent for Chunmao Yuan in 2018)the"Light of the West"Talent Cultivation Program of Chinese Academy of Sciences for Chunmao Yuan(No.RZ[2020]82)the 100 Leading Talents of Guizhou Provinee(fund for Y.M.L)the Guizhou Provincial Engineering Research Center for Natural Drugs.
文摘Eleven biogenetically related polyprenylated acylphloroglucinols(PPAPs),including four novel skeletons(1-4)and five new com-pounds(5-9),were isolated from the flowers of Hypericum monogynum.Hypermonones A-D(1-4)represented the first example of a unique dilactone structure containing carbonyl bonded single 5-lactone and tricyclic γ-lactone moieties.Their structures were elucidated by NMR analysis,X-ray crystallography,and ECD calculations.Moreover,we revised the structure of hyperibrin B to hy perm on one I(9)via NMR an alysis,a qua ntum computational chemistry method,and hypothetic bios yn thetic con siderations.Three compounds(5,6,and 9)with significant MDR reversal activity(RF ranging from 61 to 223)were superior to the positive control verapamil(MCF-7/ADR,RF:53;HepG2/ADRz RF:124).Mechanism study for compound 5 indicated that this compound could inhibit the function of P-gp tran sport rather tha n its expressi on,and the possible recog nition mechanism betwee n compo und 5 and P-gp was predicted by molecular docking.
文摘A novel class of molecules with structure N-（3-arylpropyl）-9,10-dihydro-9-oxoacridine-4-carboxamides （20- 29） were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design software. The designed molecules were synthesized by a novel synthesis route and evaluated for their inhibitory effects on the transport activity of P-glycoprotein （P-gp） by standard Hoechst 33342 assay method. Based on the pIC50 values of ten title compounds screened, three compounds exhibited better activity as compared to Verapamil used as standard.
