| Abstract: |
Geometric isomers of 2, 11-bis(morpholinomethyl)tetrahydrodipyrazino[1, 2-a:2′, 1′-c]pyrazine-1, 3, 10, 12-(2H, 4H, 9H, 1 1H)-tetrone (3 and 4) and the parent bisimides (1 and 2) were studied for their stereoselective antimetastatic activity in the Lewis Lung carcinoma model. The morpholinomethyl cis-syn-trans isomer 4 was more effective as an inhibitor of metastasis than the other three analogues. Using a postamputation protocol, the order of decreasing activity was cis morpholinomethyl analogue 4 > trans morpholinomethyl analogue 3 > parent cis imide 2 > parent trans imide 1. Increased activity observed for the morpholinomethyl derivatives may reflect differences in solubility and delivery (prodrug) or an intrinsic antitumor activity of the morpholinomethyl-N functionality. © 1985, American Chemical Society. All rights reserved. |
| Keywords: |
cancer chemotherapy; drug efficacy; nonhuman; antineoplastic agents; comparative study; antineoplastic agent; mouse; animal; mice; lung neoplasms; animal experiment; animal model; drug screening; structure activity relation; structure-activity relationship; histology; piperazines; autopsy; therapy; lewis carcinoma; stereochemistry; stereoisomerism; respiratory system; drug comparison; intraperitoneal drug administration; new drug; female; priority journal; preliminary communication; tetrahydro 2,11 bis(morpholinomethyl)dipyrazino[1,2 a:2',1' c]pyrazine 1,3,10,12(2h,4h,9h,11h) tetrone; tetrahydrodipyrazino[1,2 a:2',1' c]pyrazine 1,3,10,12(2h,4h,9h,11h) tetrone
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