Small molecules inhibitors of RAD51
Embodiments concern methods and small molecule compositions for selectively inhibiting RAD51-mediated D-loop formation while preserving RAD51's ability to form nucleoprotein filaments. The selective RAD51 D-loop formation activity inhibitors DNA repair while minimizing replication-associated toxicity in normal tissue.
1. A method for inhibiting RAD51 D-loop-formation activity in a ovarian cell comprising providing to said cell an effective amount of a RAD51 inhibitor, wherein the RAD51 inhibitor is a compound of formula (I):
wherein R 1 is hydrogen, hydroxyl, ether, halo-alkyl ether, nitro, amine, alkylamine, dialkylamine, or heterocycle;
R 2 is hydrogen, nitro, or amine;
R 3 and R 4 are independently selected from hydrogen, halogen, hydroxyl, ether, halo-alkyl ether, alkoxyalkyl, or 2-oxy-2-methylpropanamide;
W is C or CH;
X is C, CH, or N;
Y is C, CH, or N;
Z is C or CH; and
A and B are H or join to form a carbocyclic ring;
or a salt, or enantiomer thereof.
2. The method of claim 1 , wherein the cancer cell is resistant to chemotherapy or radiation.
3. The method of any of claim 1 , wherein the cell is in a patient.
4. The method of claim 3 , wherein the patient is a cancer patient.
5. The method of claim 3 , wherein the patient has been determined to have chemotherapy- or radiation-resistant cancer.
6. The method of claim 1 , wherein the cells have been treated or will be treated with a DNA damaging agent.
7. The method of claim 6 , wherein the DNA damaging agent is a cross linking agent, an alkylating agent, nitrosourea, anti-metabolite, plant alkaloid, plant extract, radiation, or radioisotope.