PHENYLHYDRAZONES WITH ANTIESTROGEN ACTIVITIES

SUBSTITUTED BENZOPHENONE PHENYLHYDRAZONES HAVE BEEN SYNTHESIZED AND HAVE DEMONSTRATED GOOD ANTIESTROGEN ACTIVITIES WITH LOW TO ABSENT INTRINSIC ESTROGENICITY (IN ANIMMATURE RAT UTERI ASSAY). 4,4(,)-DIHYDROXYBENZOPHENONE-2, 4-DINITROPHENYLHYDRAZONE (A-007) HAS DEMONSTRATED A 38-PERCENT CR WITH AN OVERALL 25- TO 50-PERCENT REDUCTION INTUMOR VOLUME OF DMBA-INDUCED RAT BREAST TUMORS. THIS IS IN CONTRAST TO A 125-PERCENT INCREASE IN TUMOR VOLUME PRODUCED BY TAMOXIFEN AND AN 850-PERCENT INCREASE SEEN IN THE CONTROLANIMALS. STUDIES USING THE COLONY-FORMING ASSAY (CFA) DOCUMENTED A-007'S ABILITY TO INHIBIT THE COLONIZATION OF HUMAN BREAST AND OVARIAN CANCERS AND NORMAL HUMAN ENDOMETRIAL CELLS. THESPECIFIC OBJECTIVES OF THIS PHASE I STUDY WILL BE TO INITIATE A-007 RAT AND MOUSE ACUTE/CHRONIC TOXICITY STUDIES AND TO DOCUMENT BONE MARROW TOXICITY OF A-007 USING THE GRANULOCYTE-MACROPHAGE COLONY-FORMING CELL ASSAY. DEKK-TEC, INC., WILL CONTINUE TO SYNTHESIZE AND SCREEN SUBSTITUTED HYDRAZONES FOR ANTIESTROGEN AND ANTICANCER PROPERTIES IN IMMATURE RATS AND IN ZR-75-1 HUMAN BREAST CANCER CELLS IN THE CFA.