Relationship between tumor (T) antigen expression and substituent effects on benzo [a] phenothiazines

Human adenovirus, oncogene-type 12 infected HEp-2 cells were exposed to six benzo[a]phenothiazines. 5-Oxo-5H-benzo[a]phenothiazine (4) and 6-hydroxy-5-oxo-5H-benzo[a]phenothiazine (5) were moderately toxic. 9-Methyl-12H-benzo[a]phenothiazine (2), 10-methyl-12H-benzo[a]phenothiazine (3), 6-methyl-5-oxo-5H-benzo[a]phenothiazine (6), and 12H-benzo[a]phenothiazine (1) were not toxic in the system tested. 6-Methyl-5-oxo-5H-benzo[a]phenothiazine (6) enhanced the expression of viral oncogene product (tumor antigen) in the adenovirus infected cells. 5-Oxo-5H-benzo[a]phenothiazine (4) and 6-hydroxy-5-oxo-5H-benzo[a]phenothiazine (5) reduced this effect. 6-Methyl-5-oxo-5H-benzo[a]phenothiazine (6), with hyperconjugation due to the methyl group, increased the T antigen activity at higher dose concentrations, whereas 6-hydroxy-5-oxo-5H-benzo[a]phenothiazine (5) with a hydroxy substituent had the opposite effect on T antigen expression. The methyl substitution at positions C9 or C10 increased the T antigen expression of adenovirus infected cells.