Building With the Molecules of Medicine

Adushan Pillay (center) with colleague Justin Omolo (left) and supervisor Carles de Koning
Adushan Pillay (center) with colleague Justin Omolo (left) and supervisor Carles de Koning

For South African organic chemistry student Adushan Pillay, conducting research for his PhD is like building with Lego children’s blocks.

“That’s what we do at a molecular level,” he said. “You can’t predict what will work – you build and build, and it’s trial and error to figure out what works.”

Pillay’s building materials are molecular compounds known as naphthoquinones found in a parasitic fungus that causes blight on potato plants. These compounds kill the host plant by producing toxins, but what’s interesting to Pillay is whether they could combat human diseases.

The 26-year-old from Pietermaritzburg in South Africa’s KwaZulu Natal province is probing the potential of these compounds to fight cancer. He has identified a specific molecule, known as marticin, which shows great promise as an anti-cancer drug, according to Pillay and his supervisor.

Pillay is studying under a program to support science in developing countries, the Science Initiative Group (SIG) of the U.S. Institute for Advanced Study. He is one of the PhD students from sub-Saharan Africa in SIG’s Regional Initiative in Science and Education (RISE) and is studying at Johannesburg’s Witwatersrand (Wits) University.

RISE has grouped scientists into networks relating to their research areas. Pillay’s work falls under SABINA, the Southern African Biochemistry and Informatics for Natural Products.

“We’re lucky to have 10 percent of the world’s biodiversity in plants here in Africa,” said Pillay. The goal of SABINA is to use this biodiversity to increase capacity in natural products research in southern Africa.

In addition to Wits, where Pillay is conducting his research, the University of Malawi, the University of Namibia, and the Tea Research Foundation of Central Africa (TRFCA) are SABINA partner institutions, along with Pretoria University and the South African Council for Scientific and Industrial Research (CSIR).

Given SABINA’s emphasis on natural products, it might seem that the focus would be on plants in nature rather than on synthesizing compounds in a lab. However, the fungus makes the key compound in very small amounts, so if its anti-cancer properties are proven, this medicinal plant will be worth a lot of money, which could lead to over-harvesting.

This is why Pillay is working so hard to make a molecule in the lab which is identical to the one found in nature – a challenge in that it is structurally complex. Such a “synthetically identical natural product” could be produced in large quantities.

To this end Pillay aims to develop a novel methodology, for the synthesis of a model tricyclic system, but he has been finding it hard to introduce the final ring to make it a naphthoquinone.

“It’s only about 30 percent of the time that you get what you want, so you get used to being disappointed,” he mused. “But if you go into something knowing that the outcome will be uncertain, then when it does work you’re on a high for three days.”

Pillay’s supervisor, Charles de Koning, professor of Organic Chemistry at the University of the Witwatersrand, harks back to that Lego analogy. “You build and build, and then if the next block doesn’t fit, you have to kick whole house down and start over.”

De Koning describes his student as “a very creative organic chemist”. “He’s in my office just about every day with new ideas on how to synthesize the complex quinones we have set as targets for his PhD. Then by the end of the week, as if by magic, he has already obtained some interesting results.”

Pillay is aware that for all his hard work his research could produce an unexpected outcome, that marticin might not be the anti-cancer drug he hopes it is.

“So I’m doing other things on the side,” he said. “I know I can’t put all my eggs in one basket.” He aims to test the compound for anti-malarial and anti fungal properties as well.

Pillay said he receives support from fellow chemistry students, especially his Tanzanian colleague in the SABINA-RISE program, Justin Omolo. Omolo in turn says he appreciates Pillay.

“I also get depressed when my research isn’t going well,” said Omolo, who is investigating the anti-HIV properties of an indigenous Tanzanian plant. “Adushan and I support each other, we tell each other that things are going to work out.”

Pillay said that one of the aspects of the RISE program that he values is the interaction with students from other African countries, who he sees as “the cream of the crop”

Story: Julie Frederikse ( August 2011), Photography: Arlen Hastings (RISE)