Module 1: Introduction to Enediyne Class of Natural Products

Lecture 1 : History of Discovery of Enediynes and History of Cancer

1.2.6. The Anticancer Antibiotics

Analysis of the number and sources of anticancer and antiinfective agents, indicates that over 60% of the approved drugs and pre-approved candidates developed in the area of these diseases are of natural origin. Drugs of natural origin have been classified as original natural products, products derived semisynthetically from natural products, or synthetic products based on natural product models. Anticancer antibiotics are drugs derived from microbial sources. Data showed that of the new approved drugs reported between 1983 and 1994 antibacterial drugs of natural origin is 78%  while 61% of the 31 anticancer drugs  are naturally-derived  or are modeled on a parent natural product. Of the 87 approved anticancer drugs, 62% are of natural origin or are modeled on natural parent products-fifteen are the original natural product, and 25 are semisynthetic derivatives including steroids, nucleosides, microbial- and plant-origin, choline and peptide derivative. Approved rest 14 anticancer drugs may be classified natural product  models. Of the 299 pre-approved anticancer drug candidates which were in preclinical or clinical development for the period 1989-1995, 50 are the original natural product of  marine-,  microbial-, and  plant source and 48 are semisynthetic derivatives of nucleosides, aniimal-, microbial-, and plant origin, while 30 are based on natural product models and 88 are biologics. Among them enediyne class of natural products are newer anticancer antibiotics.

Over the past ten years there has been a rapid escalation in the discovery of molecular targets that may be applied to the discovery of novel tools for the diagnosis, prevention, and treatment of human diseases. With the sequencing of the human genome, there has been an explosion in the knowledge of combinatorial synthesis and screening to select the active drug candidates including anticancer agents.Therefore now a day many new drugs are coming up which are already approved or in clinical or pre-clinical trial. Some important examples of anticancer drugs are given below.

(a) Anthracyclines

Figure 1. Chemical structures of anthracyclin class of anticancer drugs

(b) Dactinomycin (Cosmegen)

(c) Plicamycin (Mithramycin)

(d) Mitomycin (Mutamycin)  

Figure 2. Chemical structures of some anticancer agents.

(e) Platinum Compound 

(f) Bleomycin (Blenoxane)

Figure 3. Chemical structure of Bleomycin.

(g) Enediynes

Figure 4. Chemical structure of Enediyne-Calicheamicin.

Below is a schematic presentation of the A-T and G-C base pairs in the minor groove with designated sites of action of various anticancer drugs (Figure 5).

Figure 5. Schematic presentation of the A-T and G-C base pairs in the minor groove with designated sites of anticancer drug action.