title: Boron betaine analogs: antitumor activity and effects on Ehrlich ascites tumor cell metabolism.
abstract: Several newly synthesized boron betaine analogs had antitumor activity in Ehrlich ascites, Walker 256 ascites carcinosarcoma, and Lewis lung screens and marginal activity in the B-16 melanotic melanoma screen. In vivo testing demonstrated that trimethylamine-cyanoborane inhibied Ehrlich ascites cell DNA and protein syntheses as well as gene modulation by chromatin protein phosphorylation and methylation. Trimethylamine-cyanoborane increased cyclic-AMP levels. In vitro testing showed that nuclear DNA polymerase, thymidylate synthetase, S-adenosylmethyltransferase, nonhistone chromatin methylation, deoxyribonuclease, ribonuclease, and cathepsin were inhibited by the boron analogs. These compounds did not demonstrate high antitumor activity at the doses employed, but blockage of methyl transfer from S-adenosylmethionine was established as a feasible method for controlling cell proliferation.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001622:Betaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis; D000242:Cyclic AMP / Q000096:biosynthesis; D004273:DNA, Neoplasm / Q000096:biosynthesis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009374:Neoplasms, Experimental / Q000188:drug therapy; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D001896:Boron Compounds; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D001622:Betaine; D002784:Cholesterol; D000242:Cyclic AMP