861597-70-8

Upstream product

• 93-40-3 (3,4-Dimethoxyphenyl)acetic acid 
• 1234216-79-5 2-amino-1-(3,4-dimethoxyphenyl)ethanone hydrobromic acid 
• 1835-02-5 2-Bromo-1-(3,4-dimethoxyphenyl)ethanone 
• 10313-60-7 3,4-dimethoxyphenylacetyl chloride 

Downstream Products

• 73663-58-8 2-(3,4-dimethoxybenzyl)-5-(3,4-dimethoxyphenyl)oxazole 
• 78004-24-7 (3,4-dimethoxy-phenyl)-acetic acid-(β-hydroxy-3,4-dimethoxy-phenethylamide) 
• 1234216-81-9 3,4-bis(3',4'-dimethoxyphenyl)-1H-pyrrol-2(5H)-one 
• 653572-66-8 3,4-bis(3,4-dimethoxyphenyl)-1H-pyrrole-2,5-dione 
• 58-74-2 Papaverine 
• 139-76-4 N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl)acetamide 

Relevant academic research and scientific papers

Structure-activity relationship study of permethyl ningalin B analogues as P-glycoprotein chemosensitizers

A novel series of permethyl ningalin B analogues were synthesized and evaluated for their P-glycoprotein (P-gp)-modulating activities in a P-gp-overexpressing breast cancer cell line (LCC6MDR). Compounds 35 and 37, which possess one methoxy group and one benzyloxy group at aryl ring C, displayed the most potent P-gp-modulating activity. A 1 μM concentration of 35 and 37 resensitized LCC6MDR cells toward paclitaxel by 42.7-fold, with respective EC50 values of 93.5 and 110.0 nM. Their mechanism of P-gp modulation is associated with an increase in intracellular drug accumulation. Their advantages also include low cytotoxicity (IC50 for L929 fibroblast >100 μM) and high therapeutic indexes (>909 after normalization with their EC50 values). 35 is not a substrate of P-gp. They are potentially dual-selective modulators for both P-gp and breast cancer resistance protein transporters. The present study demonstrates that these new compounds can be employed as effective and safe modulators of P-gp-mediated drug resistance in cancer cells.

Design and syntheses of permethyl ningalin B analogues: Potent multidrug resistance (MDR) reversal agents of cancer cells

A series of novel N-arylalkyl-3,4-diaryl-substituted pyrrole-2,5-diones were synthesized. They exhibited promising P-gp modulating activity in a P-gp overexpressing breast cancer cell line (LCC6MDR). Compound 6 (with three methoxy groups at D-ring) displayed the highest P-gp modulating activity. 6 at 1 μM can sensitize LCC6MDR cells toward paclitaxel by 18.2-fold. Interestingly, a synergy on modulating P-gp was noted when 6 and 25 were used together (fractional inhibitory concentration index FICI = 0.42). Combination of 6 (0.5 μM) and 25 (0.5 μM) resulted in a 66-fold sensitization of LCC6MDR cells toward paclitaxel. They also reversed P-gp mediated doxorubicin (DOX) and vincristine resistance. Kinetic characterization suggests that permethyl ningalin B analogues likely act as a noncompetitive inhibitor of P-gp-mediated DOX transport (Ki = 5.4-5.8 μM). The present study demonstrates that synthetic analogues of permethyl ningalin B can be employed as effective and safe modulators of P-gp-mediated drug resistance in cancer cells.