University Students' Reasons for NOT Drinking: Relationship to Alcohol Consumption Level.

Abstract

Out of a series of fourteen 1,2,4-triazolo(4,3-b)-, and 1,2,3,4-tetrazolo-(1,5-b)pyridazine derivatives, 4 compounds have been found to reveal high cytostatic activity in KB and HeLa human cancer cell lines in vitro with ED50 activity values ranging from 0.25 to 3.0 micrograms/cm3 (0.009-0.158 x 10(-4) mole/l), and according to DR and D, NCI, NIH Bethesda criterion were qualified for further in vivo screening investigation. 6-Chloro-8-(N,N-dimethylaminosulfonylmethyl)-1,2,3,4-tetrazolo+ ++-(1,5-b)- pyridazine exhibited the strongest in vitro cytostatic activity (ED50 = 0.009 x 10(-4) mole/l), comparable with the best standards, and higher in comparison with a standard cytosine arabinoside (ED50 = 0.03-0.04 x 10(-4) mole/l). The presence of chlorine atom at C-6 position in the pyridazine ring determines the cytotoxic activity of tetrazolopyridazines as the primary factor and C-8 substituents, which influence their better solubility seems to be a secondary one, as confirmed by the results of the structure-activity and solubility-activity relationship analysis. However, for the exhibition of the triazolopyridazine activities the presence of two chlorine atoms at C-6 and C-3 position was essential.