In Vitro Evaluation of the Novel Chemotherapeutic Agents U-73, 975, U-77, 779, and U-80, 244 in Gynecologic Cancer Cell Lines

Abstract

U-73, 975 (U-73), U-77, 779 (U-77), and U-80, 244 (U-80) are analogs of the potent antitumor compound CC-1065. This class of drugs act us alkylating agents binding to DNA preferentially. Using the ATP-chemosensitivity assay, this study wus designed to compare the potencies of U-73, U-77, and U-80 with cisplatin (DDP) or adriamycin (DXR) in 10 gynecologic cancer cell lines. The mean IC50s were: U-73, 0.173 2 0.115 ng/ml; U-77, 0.650 ± 0.209 ng/ml; U-80, 3.0 ± 3.0 ng/ml; DDP, 4.40 ± 2.83 μg /ml; and DXR, 0.286 ± 0.040 μg /ml. U-73 appears the most potent analog, being 10³ to 10⁴ times more cytotoxic than DDP and DXR. U-77 and U-80 were somewhat comparable, demonstrating approximately 10² to 10³ greater potency than DDP and DXR. All the cervical, endometrial, und ovarian cell lines were sensitive to U-73, with decreasing sensitivity to U-77, U-80, DXR, and DDP in that order. U-73 as well as the other analogs appear promising chemotherapeutic agents.