TUBERCULOSIS - A SEARCH FOR NOVEL THERAPY STARTING WITH NATURAL-PRODUCTS

The reemergence of tuberculosis and closely related diseases as signif icant public health problems is briefly reviewed with particular empha sis on the exacerbating role of AIDS and multiple drug resistance. Scr eening methods available for discovering new chemical entities active against resistant strains are discussed and their use in screening ext racts and compounds for activity is illustrated with a number of newly discovered structures being presented. In particular, the properties of the potent and structurally novel indoloquinazolinone alkaloid, try ptanthrin, is described. Many analogs of this lead structure were synt hesized by combinatorial and multiple parallel synthetic techniques an d evaluated in vitro and in vivo for their potential in the chemothera py of human infections. (C) 1998 John Wiley & Sons, Inc.