ABSTRACT
The research team of Dr. Monroe E. Wall and Dr. Mansukh C. Wani of Research Triangle Institute discovered two first-in-class life-saving chemotherapeutic agents. Camptothecin, first isolated and identified from Camptotheca acuminata, was found to kill cancer cells uniquely via topoisomerase I poisoning. Presently, two first-generation analogues of camptothecin are used to treat ovarian, colorectal, and small-cell lung cancers, and several second-generation analogues are in clinical trials. Taxol, first isolated and identified by Wall and Wani from Taxus brevifolia, was found to inhibit cancer cell growth via the stabilization of microtubules. In 1992, taxol was approved for refractory ovarian cancer and today is used against breast and non-small cell lung cancers and in Kaposi's sarcoma. While there have been numerous reviews of these molecules individually, this review offers an integrated account of the research team of "Wall and Wani" and the significance of their discoveries to chemistry, biology, and clinical medicine.
Subject(s)
Antineoplastic Agents, Phytogenic/history , Biological Products/history , Camptothecin/history , Paclitaxel/history , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Biological Products/chemistry , Biological Products/pharmacology , Camptotheca/chemistry , Camptothecin/chemistry , Camptothecin/pharmacology , Drug Screening Assays, Antitumor , Enzyme Inhibitors/history , History, 20th Century , Humans , Paclitaxel/chemistry , Paclitaxel/pharmacology , Taxus/chemistry , Topoisomerase I InhibitorsABSTRACT
Camptothecin (CPT) and taxol are secondary metabolites found in the stembark of Camptotheca acuminata, a native of China, and Taxus brevifolia, found in the northwest Pacific coastal region of the USA, respectively. The compounds were isolated through bioassay-guided fractionation of various extracts and through chromatographic fractions. Their unique and hitherto unknown structures were elucidated by nuclear magnetic resonance, mass spectrometry and X-ray analysis. Both compounds have unique mechanisms of antitumor activity; CPT uniquely inhibits an enzyme, topoisomerase I, involved in DNA replication, while taxol binds to a protein, tubulin, thus inhibiting cell division. Taxol has been called the best new anticancer agent developed from natural products, showing particular efficacy against ovarian cancer. CPT and analogs singly or combined with cisplatinum show efficacy against solid tumors, breast, lung, and colorectal, which hitherto have been unaffected by most cancer chemotherapeutic agents.
Subject(s)
Antineoplastic Agents, Phytogenic , Camptothecin , Paclitaxel , Antineoplastic Agents, Phytogenic/history , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/history , Camptothecin/isolation & purification , Camptothecin/pharmacology , Camptothecin/therapeutic use , Cell Division/drug effects , Chemistry, Analytic/methods , Chemistry, Pharmaceutical/methods , Clinical Trials as Topic , Countercurrent Distribution , Enzyme Inhibitors/history , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , History, 20th Century , Humans , Molecular Structure , Neoplasms/drug therapy , Paclitaxel/history , Paclitaxel/isolation & purification , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Structure-Activity Relationship , Topoisomerase I Inhibitors , Tubulin Modulators , United StatesABSTRACT
Camptothecin and taxol are secondary metabolites found, respectively, in the wood bark of Camptotheca acuminata, a native of China, and Taxus brevifolia, found in the northwest Pacific coastal region of the United States. The compounds were isolated guided by bioassay on various extracts and chromatographic fractions. Their unique and hitherto unknown structures were elucidated by nuclear magnetic resonance, mass spectrometry, and X-ray analysis. Both compounds have unique mechanisms of antitumor activity; camptothecin uniquely inhibits an enzyme, topoisomerase I, involved in DNA replication. Taxol binds to a protein, tubulin, thus inhibiting cell division. Taxol has been called the best new anticancer agent developed from natural products, showing particular efficacy against ovarian cancer. Camptothecin and analogues singly or combined with cisplatin show efficacy against solid tumors, breast, lung, and colorectal, which hitherto have been unaffected by most cancer chemotherapeutic agents.
