In vitro evaluation of the novel chemotherapeutic agents U-73,975, U-77,779, and U-80,244 in gynecologic cancer cell lines.

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 as alkylating agents binding to DNA preferentially. Using the ATP-chemosensitivity assay, this study was 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 +/- 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 micrograms/ml; and DXR, 0.286 +/- 0.040 micrograms/ml. U-73 appears the most potent analog, being 10(3) to 10(4) times more cytotoxic than DDP and DXR. U-77 and U-80 were somewhat comparable, demonstrating approximately 10(2) to 10(3) greater potency than DDP and DXR. All the cervical, endometrial, and 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.