POTENTIATION OF THE ANTI-TUMOR ACTIVITY OF 2-FORMYLPYRIDINE THIOSEMICARBAZONE BY METAL CHELATION - 2-FORMYLPYRIDINE THIOSEMICARBAZONE ZINC-SULFATE (NSC 294721)

A Zn chelate of 2-formylpyridine-thiosemicarbazone (2-FPTS-Zn) has been synthetized and its antitumour activity has been investigated on a spectrum of tumours transplantable in mice: the ascitic from of L1210 lymphoid leukemia, the ascitic and blood forms of P388 lymphocytic leukemia and solid tumours such as Melanoma B16 and Lewis lung carcinoma. The therapeutic activity of the chelate was compared to that of the free drug against leukemias. The following activities were established. The 2-FPTS-Zn chelate showed a higher therapeutic activity against leukemias as compared to the free drug. Treatment with the chelate induced a high percentage of increase in life span (151-157%) of L1210 leukemia bearing mice over controls and a high percentage of long-term survivals in treated groups (10-40%) was recorded when the optimal schedule of treatment was used (6-8 mg/kg given every 3 hr on days 1, 5 and 9 after tumour cells inoculation). The Zn chelate significantly inhibited the formation of lung metastases in the Lewis lung tumour and was inactive against the B16 tumour under the conditions of the experiment. A good direct contact between the chelate and the tumour cells seemed to be required to induce therapeutic activity. © 1979.