Stereoselective effects of cis- and trans-cyclopropylbis(dioxopiperazines) related to ICRF-159 on metastases of a hamster lung adenocarcinoma

Abstract
The synthesis for cis-4,4''-(1,2-cyclopropanediyl)bis(2,6-piperazinedione) (cis-3) is discussed. Stereoselective effects on metastases of cis-3 and the previously reported trans-2 isomer were compared to conformationally mobile ICRF-159 [4,4''-(1-methyl-1,2-ethanediyl)bis(2,6-piperazinedione)] using a Syrian hamster lung adenocarcinoma (LG1002). Whereas ICRF-159 and cis-3 significantly inhibited lung metastases, the trans-2 isomer significantly increased the number of metastatic nodules in the lung. Antimetastatic activity can be separated from metastatic potentiating activity by controlling drug geometry.