A Lazarus natural product from an Ethiopian medicinal plant

By Fekadu Fullas (PhD)

In the medical world, there is a phrase known as the “Lazarus phenomenon” to describe a rare situation where a person comes back to life (spontaneous self-resuscitation) after completely shutting down (in yet another common parlance, after going down the drain). The phrase is derived from the biblical Lazarus of Bethany, who was allegedly brought back to life from the dead. The term has also been used generically to describe other similar situations.

In a recent American Society of Pharmacognosy (ASP) newsletter (Vol 53, Issue 1), natural product scientist David Newman highlighted maytansine as a “Lazarus compound.” The anticancer molecule was originally isolated from the Ethiopian medicinal plant Maytenus serrata (locally known as qoqba). Lazarus, because once dubbed dead and abandoned by the natural product research community due to its diminished activity in later trials, maytansine now seems to be resurrected back to life a la Lazarus.

In the 1970’s, the National Cancer Institute (NCI) in the USA launched an extensive project to comb the world flora in search of potential anticancer molecules which could then be developed into modern agents. Parenthetically, it should be noted that about 49% of the 175 or so modern cancer drugs available today in hospitals and cancer treatment centers were developed from prototype compounds from nature. It turned out that qoqoba was one of the thousands of plant specimens that the NCI put through a battery of cancer screen cell lines. After further clinical trials, the bioactive maytansine was dropped due to insufficient activity. According to the ASP newsletter article, in 2013 a small biotech company re-picked up the a slightly modified version of maytansine and hooked it up on a monoclonal antibody (MAb) to deliver it to a key locus on the cancer oncogene. Newman likens the maytansine derivative to a warhead on an MAb delivery system. The agent was developed as Herceptin®, fast tracked and approved by FDA as a drug for the treatment of metastatic breast cancer. According to the newsletter, a variety of other monoclonal antibody-linked maytansinoid congeners directed against certain receptors in a variety of cancer types are in on-going clinical trials.

Indeed, what a comeback natural product that traces back its origin to the Ethiopian medicinal plant qoqoba (M. serrata)!