CAMPTOTHECIN AND TAXOL - FROM DISCOVERY TO CLINIC

Camptothecin (CPT) and taxol are secondary metabolites found in the st embark of Camptotheca acuminata, a native of China, and Taxus brevifol ia, found in the northwest Pacific coastal region of the USA, respecti vely. The compounds were isolated through bioassay-guided fractionatio n of various extracts and through chromatographic fractions. Their uni que and hitherto unknown structures were elucidated by nuclear magneti c resonance, mass spectrometry and X-ray analysis. Both compounds have unique mechanisms of antitumor activity; CPT uniquely inhibits an enz yme, topoisomerase I, involved in DNA replication, while taxol binds t o a protein, tubulin, thus inhibiting cell division. Taxol has been ca lled the best new anticancer agent developed from natural products, sh owing particular efficacy against ovarian cancer. CPT and analogs sing ly or combined with cisplatinum show efficacy against solid tumors, br east, lung, and colorectal, which hitherto have been unaffected by mos t cancer chemotherapeutic agents.