3-(CARBOXYALKYLTHIO) RIFAMYCIN-S AND RIFAMYCIN-SV DERIVATIVES INHIBITHUMAN NEUTROPHIL FUNCTIONS

In order to further investigate the potential of rifamycins as antiinf lammatory drugs, twenty-five semisynthetic rifamycins were tested at c oncentrations ranging from 10(-9) to 10(-5) M on in vitro human neutro phil functions such as locomotion, superoxide anion production, and de granulation, under different stimulatory conditions. They were also te sted as antiproliferative agents on peripheral blood lymphocytes. The present semisynthetic derivatives are in general characterized by thei r carrying a hydrophilic substituent; they are rifamycin S or rifamyci n SV derivatives carrying at C(3) either a carboxyalkyl side-chain or a glycosyl side-chain. Derivatives of the former group displayed inhib itory activities covering the whole range of activities tested, sugges ting that the sum of these different effects could support their antii nflammatory activity in vivo. These derivatives, carrying a free carbo xyl, are more water soluble than rifamycin SV at physiological pH, and may serve as antiinflammatory drugs for local administration, alterna tive to rifamycin SV, possibly giving higher efficacy and reduced side effects of pain and tissue swelling.