Tea polyphenol esters and analogs thereof for cancer prevention and treatment
AssigneeUniversity of South Florida
InventorsQ. Ping Dou, Sangkil Nam, David M. Smith
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Abstract
Disclosed herein are ester-bond containing tea polyphenols that has a susceptibility to nucleophilic attack, their analogs and pharmaceutically acceptable salts, method for inhibiting proteasomal chymotrypsin-like activity in vivo and in vitro, methods for cancer treatment with tea-derived polyphenols, such as EGCG, ECG, GCG, or CG, as well as pharmaceutical compositions comprising the same.
Claims15
A method for inhibiting the proteasomal chymotrypsin activity but not the proteasomal trypsin activity in a cell, comprising contacting the cell with an effective amount of a polyphenol having an ester bond that has a susceptibility to nucleophilic attack,
- wherein the polyphenol compound is
- and verifying that proteasomal chymotrypsin activity has been inhibited.
A method for inhibiting the proteasomal chymotrypsin activity but not the proteasomal trypsin activity in a cell, comprising contacting the cell with an effective amount of a polyphenol having an ester bond that has a susceptibility to nucleophilic attack;
- wherein the polyphenol ester has a structure selected from the group consisting of:
- wherein each R is independently —H, —OH, —NH, —OMe, —CH2OH, —CH2NH2, or -gallate;
- and
- wherein each R′ is independently ═O, —H, —OH, —HN2, —OMe, —CH2OH, —CH2NH2, or -gallate;
- and
- verifying the proteasomal chymotrypsin activity has been inhibited.
A method for inhibiting the proteasomal chymotrypsin activity but not the proteasomal trypsin activity in a cell, comprising contacting the cell with an effective amount of a compound having the formula:
- wherein R and R1 are each independently —H or -gallate;
- and verifying that proteasomal chymotrypsin activity has been inhibited.
A method for inhibiting the proteasomal chymotrypsin activity but not the proteasomal trypsin activity cell in a patient having a cancer, comprising administering to the patient an effective amount of a compound having the formula:
- wherein R and R1 are each independently —H or -gallate or a pharmaceutically-acceptable salt thereof;
- and
- observing an effect of proteasomal chymotrypsin inhibition in the patient.
A method for inhibiting selectively proteasomal chymotrypsin or chymotypsin-like activity in a neoplastic cell comprising contacting a neoplastic cell exhibiting chymotrypsin or chymotrypsin-like activity with an effective amount of at least one phenolic substance which bears a carboxylic acid ester bond that is susceptible to nucleophilic attack, or an analog thereof, wherein
- the phenolic substance is
- or combinations thereof.
A method for inhibiting selectively proteasomal chymotrypsin or chymotypsin-like activity in a neoplastic cell comprising contacting a neoplastic cell exhibiting chymotyrpsin or chymotyrpsin-like activity with an effective amount of at least one phenolic substance which bears a carboxylic acid ester bond that is susceptible to nucleophilic attack, or an analog thereof, wherein
- the analog of the phenolic substance is selected from at least one compound of the formula (1)-(28), in which R can be H, —OH, —NH2, —OCH3, —CH2OH, —CH2NH2, or -gallate and R′ can be the same as or different from R and, in addition, together with the carbon atom to which it is attached, can be C═O.
A method for arresting a tumor cell at a G1-phase or inducing tumor cell apoptosis comprising contacting a tumor cell with an effective amount of an analog of a phenolic substance found in tea, wherein said analog of the phenolic substance is selected from at least one compound of the formula (1)-(28), in which R can be H, —OH, —NH2, —OCH3, —CH2OH, —CH2NH2, or -gallate and R′ can be the same as or different from R and, in addition, together with the carbon atom to which it is attached, can be C═O.
Dependencies are inferred from the claim text.