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Antileukemic action of new aromatic bisguanylhydrazone derivatives
Author(s) -
Mihich E.
Publication year - 1967
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(1967)20:5<880::aid-cncr2820200548>3.0.co;2-c
Subject(s) - medicine , potency , methylglyoxal , pharmacology , therapeutic index , toxicity , l1210 cells , drug , chemotherapy , urea , mechanism of action , neoplasm , in vitro , biochemistry , cytotoxicity , chemistry , pathology , enzyme
The clinical usefulness of methylglyoxal‐bis(guanylhydrazone) (CH 3 ‐G) as an antileukemic agent is reduced by its substantial toxicity. Of more than 200 analogues of CH 3 ‐G tested, none showed significant antileukemic effects in mice. Two aromatic bisguanylhydrazones with borderline activity had marked effects against leukemia L1210 in DBA/2 Ha mice when given in combination with hydroxystilbamidine. Since the diamidine had only borderline activity when given alone, this represents an unusual example of synergism in cancer chemotherapy. A new drug, 4,4′‐diacetyl‐diphenyl‐urea‐bis(guanylhydrazone) (DDUG) showed marked activity against L1210: many of DBA/2 Ha mice survived. On a molar basis the LD 50 ′s of DDUG and CH 3 ‐G were comparable. Similar antileukemic effects were obtained with doses of DDUG 15‐to‐20‐fold smaller than doses of CH 3 ‐G. No cross‐resistance was apparent between DDUG and CH 3 ‐G. Because of its potency and its highly favorable therapeutic index, DDUG deserves clinical trial.