A.4.
Cisplatin and other platinum drugs
Cisplatin,
cis-dichlorodiammine platinum(II)
(Fig. 1.4), is the grandparent of all platinum drugs. It is a widely prescribed
anticancer drug with therapeutic activity against various solid tumors, but
also with substantial side effects. The anticancer activity of cisplatin was
discovered by Dr. Barnett Rosenberg of Michigan State University in 1965 [2]. In 1978, the first formulated pharmaceutical
product of cisplatin, Platinol, was approved by the FDA and sold by
Byistol-Myer Squibb.
As
an alkylating agent, the platinum ion of cisplatin forms coordination bonds
mostly with guanine on DNA. This crosslinking causes the interference of DNA
replication, thus, inhibits the replication of cancer cells.
Fig. 1.4 Cisplatin,
carboplatin, and oxaliplatin
Since
the discovery of cisplatin’s anticancer activity, thousands of cisplatin
analogues have been made and/or studied. Two of the notable platinum drugs
successfully developed by Bristol-Myers Squibb are carboplatin and oxaliplatin
(Fig. 1.4); both were approved by the FDA for treating a variety of cancers.
In
the last thirty years or so, the impact of platinum drugs on cancer treatment
has been tremendous and has benefited many cancer patients. However, because
platinum drugs are often associated with significant side effects, scientists
are still working on finding better platinum compounds with fewer/less side
effects. Currently, there are a number of new platinum drugs under
investigation or development, including some of the platinum compounds
synthesized by one of the co-authors, Dr. Jiajiu Shaw. A couple of these new platinum
compounds are shown in Fig. 1.5. The dinuclear platinum compound is the first
to show a coordination bond between the amide oxygen and platinum(II).
Fig. 1.5 Examples
of a 3-Nitrogen Pt compound (left) and a dinuclear Pt compound (right)
© Jiajiu Shaw, 2018
Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen.
