Synthesis and antitumor activity of vitamin B1 derivatives containing ferrocene fragment

Ferrocenes as potential anticancer drugs. Facts and hypotheses

“…140 At the same time, the study of intensity of DNA synthesis processes by the 3 H thymidine test on sarcoma 37, MH 22a hepatoma, and P388 leukemia established that the conjugates of this compound with thiamines activate the DNA synthesis. 140…”

Antitumor activities of ferrocene compounds

“…Sodium (diferrocenyl)dithiophosphinic acid Na + (Fc 2 PS 2 ) -, in which the ferrocene fragments are parts of the anion, i.e., have an overall negative charge, showed no antitumor activity in vivo against Ehrlich ascites carci noma model upon subcutaneous administration. 76 In in vitro studies of the intensity of DNA synthetic processes by the 3 H thymidine test (the 3 H thymidine or antiproliferative test is used to estimate the intensity of incorporation into DNA of tritium labeled thymidine nucleoside, 3 H thym ine ribose) on sarcoma 37, hepatoma mh 22a, and Р388 leukosis tumor cells, it was found that ferrocene deriva tives of thiamine (11a) and (hydroxy)thiamine (11b)* ac tivate the synthesis of DNA, which is especially noticeable on short term treatment (3 h). 76 On subcutaneous administration of thiamine and (hydroxy)thiamine(diferrocenylduithiophosphinates) (11a,b), both compounds were found to have low toxicity with LD 50 exceeding 1000 mg kg -1 (exact LD 50 values could not be determined due to sparing solubility of the agents in water).…”

“…76 In in vitro studies of the intensity of DNA synthetic processes by the 3 H thymidine test (the 3 H thymidine or antiproliferative test is used to estimate the intensity of incorporation into DNA of tritium labeled thymidine nucleoside, 3 H thym ine ribose) on sarcoma 37, hepatoma mh 22a, and Р388 leukosis tumor cells, it was found that ferrocene deriva tives of thiamine (11a) and (hydroxy)thiamine (11b)* ac tivate the synthesis of DNA, which is especially noticeable on short term treatment (3 h). 76 On subcutaneous administration of thiamine and (hydroxy)thiamine(diferrocenylduithiophosphinates) (11a,b), both compounds were found to have low toxicity with LD 50 exceeding 1000 mg kg -1 (exact LD 50 values could not be determined due to sparing solubility of the agents in water). 76 * 4 Methyl 3 [2 methyl 4 aminopyrimidyl 5)methyl] 5 (2 hydroxyethyl)thiazolium (thiamine is Vitamin В 1 , R = NH 2 ); 4 methyl 3 [2 methyl 4 hydroxypyrimidyl 5)methyl] 5 (2 hydroxyethyl)thiazolium ((hydroxy)thiamine is Vitamin В 1 antagonist, R = OH, has antitumor activity).…”