ABSTRACT
The functional components in soymilk may vary depending upon the fermentation process. A fermented soymilk product (FSP) obtained by incubation with the microorganisms of intestinal microflora was found to reduce the risk of breast cancer. Guided by the inhibitory activities against breast cancer cells, two cytotoxic compounds, daidzein and (S)-latifolicinin A, were isolated from the FSP by repetitive extraction and chromatography. Latifolicinin A is the n-butyl ester of ß-(4-hydroxyphenyl)lactic acid (HPLA). A series of the ester and amide derivatives of (S)-HPLA and L-tyrosine were synthesized for evaluation of their cytotoxic activities. In comparison, (S)-HPLA derivatives exhibited equal or superior inhibitory activities to their L-tyrosine counterparts, and (S)-HPLA amides showed better cytotoxic activities than their corresponding esters. In particular, (S)-HPLA farnesyl amide was active to triple-negative MDA-MB-231 breast cancer cells (IC50 = 27 µM) and 10-fold less toxic to Detroit-551 normal cells.
Subject(s)
Amides/chemistry , Amides/pharmacology , Breast Neoplasms/physiopathology , Cell Proliferation/drug effects , Glycine max/microbiology , Lactates/chemistry , Lactates/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Soy Milk/chemistry , Soy Milk/pharmacology , Amides/metabolism , Cell Line, Tumor , Female , Fermentation , Growth Inhibitors/chemistry , Growth Inhibitors/metabolism , Growth Inhibitors/pharmacology , Humans , Lactates/metabolism , Lactobacillus/metabolism , Plant Extracts/metabolism , Saccharomyces cerevisiae/metabolism , Glycine max/chemistry , Structure-Activity RelationshipABSTRACT
Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the P1 site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent and selective FAP inhibitor is needed in evaluating that FAP as a therapeutic target. Therefore, it is important to develop selective FAP inhibitors for the use of target validation. To achieve this, optimization of the nonselective DPP-IV inhibitor 8 led to the discovery of a new class of substituted 4-carboxymethylpyroglutamic acid diamides as FAP inhibitors. SAR studies resulted in a number of FAP inhibitors having IC(50) of <100 nM with excellent selectivity over DPP-IV, DPP-II, DPP8, and DPP9 (IC(50) > 100 µM). Compounds 18a, 18b, and 19 are the only known potent and selective FAP inhibitors, which prompts us to further study the physiological role of FAP.
Subject(s)
Amides/chemical synthesis , Gelatinases/antagonists & inhibitors , Membrane Proteins/antagonists & inhibitors , Pyrrolidonecarboxylic Acid/analogs & derivatives , Pyrrolidonecarboxylic Acid/chemical synthesis , Amides/pharmacokinetics , Amides/pharmacology , Animals , Dipeptidases/antagonists & inhibitors , Dipeptidyl-Peptidase IV Inhibitors , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/antagonists & inhibitors , Endopeptidases , Humans , Mice , Mice, Inbred BALB C , Pyrrolidonecarboxylic Acid/pharmacokinetics , Pyrrolidonecarboxylic Acid/pharmacology , Serine Endopeptidases , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Linear-like and photoluminescent polyethylenimines (LPEIs) were synthesized through a one-pot reaction within 5 min using synchrotron radiation for intracellular imaging and siRNA delivery.
Subject(s)
Luminescent Agents/chemical synthesis , Polyethyleneimine/chemical synthesis , RNA, Small Interfering/administration & dosage , Cell Line, Tumor , Cyclin B1/genetics , Gene Silencing , Humans , Luminescent Agents/chemistry , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Polyethyleneimine/chemistry , RNA, Small Interfering/geneticsABSTRACT
A specific ion-pair approach can be involved in precise control of the size of gold nanodots. The dendrimers with terminal amine and hydroxyl groups were a hydrophilic and hydrophobic microcavity-template, respectively, for trapping gold salts. The facile strategy can significantly enhance the quantum yield of gold nanodots from 20% to 62% after microwave irradiation.
