Compounds and methods for inhibition of ap endonuclease-1/redox factor-1 (hape1) activity
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsBarry I. Gold, Xiangqun Xie, Ajay Srinivasan, LiRong Wang
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Abstract
A method for treating a neoplasm in a subject, comprising co-administering to the subject a therapeutically effective amount of an anticancer agent and a substituted 6,7-methylenedioxy-4-amino-quinoline, or a pharmaceutically acceptable salt or ester thereof.
Claims34
A method of inhibiting AP endonuclease-1/redox factor-1 (NAPE 1) activity comprising application of a compound having the structure
- wherein domain A has the structure
- wherein R1 is H, a C1-C5 alkyl group, which can be branched, unbranched, cyclic or acyclic, or a 3-5 member ring, which can be homocyclic or heterocyclic;
- the linker is a flexible or rigid linking group;
- and
- domain B includes a portion that is suitable to form a π-cation interaction with Arg177.
A method of inhibiting AP endonuclease-1/redox factor-1 (hAPE1) activity comprising application of a compound having the structure
- wherein R1 is H, a C1-C5 alkyl group, which can be branched, unbranched, cyclic or acyclic, or a 3-5 member ring, which can be homocyclic or heterocyclic;
- R2 is H, or a C1-C5 branched, unbranched, cyclic or acyclic alkyl group;
- and R3 and R4 are independently and separately H, a C1-C5 alkyl group, which can be branched, unbranched, cyclic or acyclic, or a 3-5 member ring, which can homocyclic or heterocyclic.
A method of inhibiting AP endonuclease-1/redox factor-1 (hAPE1) activity comprising application of a compound having the structure:
A compound having the structure:
- wherein R1 is H, a C1-C5 alkyl group, which can be branched, unbranched, cyclic or acyclic, or a 3-5 member ring, which can homocyclic or heterocyclic;
- R2 is H, or a C1-C5 branched, unbranched, cyclic or acyclic alkyl group;
- and R3 and R4 are independently and separately a C1-C5 alkyl group, which can be branched, unbranched, cyclic or acyclic, or a 3-5 member ring, which can homocyclic or heterocyclic.
A method for treating cancer in a subject, comprising co-administering to the subject a DNA damaging anticancer agent and a compound having a structure of:
- wherein domain A has the structure
- wherein R1 is H, a C1-C5 alkyl group, which can be branched, unbranched, cyclic or acyclic, or a 3-5 member ring, which can be homocyclic or heterocyclic;
- the linker is a flexible or rigid linking group;
- and
- domain B includes a portion that is suitable to form a n-cation interaction with Arg177.
A method for enhancing the toxicity of a DNA methylating agent in a cell, comprising contacting the cell with a DNA alkylating agent and a compound having a structure of:
- wherein domain A has the structure
- wherein R1 is H, a C1-C5 alkyl group, which can be branched, unbranched, cyclic or acyclic, or a 3-5 member ring, which can be homocyclic or heterocyclic;
- the linker is a flexible or rigid linking group;
- and
- domain B includes a portion that is suitable to form a n-cation interaction with Arg177.
A method for treating a neoplasm in a subject, comprising co-administering to the subject a therapeutically effective amount of an anticancer agent and a substituted 6,7-methylenedioxy-4-amino-quinoline, or a pharmaceutically acceptable salt or ester thereof.
A method for treating a neoplasm in a subject, comprising administering to the subject a therapeutically effective amount of a substituted 6,7-methylenedioxy-4-amino-quinoline, or a pharmaceutically acceptable salt or ester thereof.
A method of inhibiting AP endonuclease-1/redox factor-1 (hAPE1) activity, comprising contacting hAPE1 with a substituted 6,7-methylenedioxy-4-amino-quinoline, or a pharmaceutically acceptable salt or ester thereof.
A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:
- wherein R1 is H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, cyano, optionally substituted heterocyclic, or halogen;
- L is linking group;
- and
- R5 is selected from:
- wherein R3 and R4 are each independently selected from H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclic, optionally substituted alkoxy, optionally substituted aryloxy, or halogen;
- and
- R6 is H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted alkoxy, or optionally substituted aryloxy;
- provided that at least one of the following substitutions is present:
- (i) R1 is optionally substituted alkyl or halogen;
- (ii) R6 is methyl;
- and/or
- (iii) R3 and R4 are each independently selected from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclic, optionally substituted alkoxy, optionally substituted aryloxy, or halogen.
Dependencies are inferred from the claim text.