[Structure-activity relationship of semi-synthetic derivatives of the PIA component of pristinamycin].

Pristinamycin is a naturally occurring streptogramin made up of 2 groups of synergistic components (PI and PII). Because these components are not water soluble, use of pristinamycin has up till now been confined to the oral route. Water soluble semisynthetic derivatives of the PIA component, appropriate for parenteral use, have lately been developed. PIA is a peptidic macrolactone. As opening of the lactone results in total loss of biologic activity, semisynthesis must spare this function and preserve the macrocycle. Reactions at 5 gamma and 5 delta yielded 4 families of derivatives. Antimicrobial activity has been studied for more than 80 compounds. Several derivatives are promising as they are water soluble and have in vitro and in vivo (mice) activities similar to those of the original PIA component.