IMMUNOMODULATION ACTIVITY OF PHENOTHIAZINES, BENZO[A]PHENOTHIAZINES AND BENZ[C]ACRIDINES

Some non-differentiation - induction benzo[a]phenothiazines and mutage nic benz[c]acridines more potently inhibited the mitogen - induced bla st transformation of human-peripheral blood lymphocytes than different iation - induction and non-mutagenic counterparts and phenothiazines. Differential absorption spectrophotometry revealed tight compex format ion between these drugs and bacterial endotoxin or mitogens. All of th ese compounds only slightly affected antibody dependent cellular cytot oxicity and natural killer cell activity, but significantly inhibited the endotoxin-or heat-killed Staphylococcus aureus induced tumor necro sis factor production by human mononuclear cells. Pretreatment of mice with these drugs protected them from lethal E. coli infection. Quantu mchemical analysis suggests a correlation between the biological activ ity of these compounds and some molecular orbital parameters such as t he charge at C7, and the ratio of polar/total surface areas.