Molecules made to order

Restructuring molecules for specific purposes -- be it symmetry of design or to develop medicinal drugs -- has come of age in India.

 
Last Updated: Saturday 04 July 2015

A drug designer: A V Rama Rao< TWO CHEMISTS in Hyderabad, working separately, have synthesised many complex organic molecules (those containing carbon) that are the basic constituent of most drugs. The chemistry of carbon is essential to understand the basis of all life, as most biological processes are mediated by organic compounds.

Govardhan Mehta, a professor of chemistry at the University of Hyderabad, and A V Rama Rao, director of the Indian Institute of Chemical Technology (IICT), specialise in applying the principles and techniques of organic chemistry for the synthesis of organic compounds with new and complicated structures. However, the orientation of their research is quite different.
Molecular architecture Mehta's research is motivated mainly by aesthetic considerations. "Designing and building a new molecule is an art," he says. "A molecule that is highly symmetrical has a certain beauty about it." He describes his work as molecular architecture -- conceiving a novel structure that combines elegance and utility and then putting it together.

Over the past 10 years, Mehta has synthesised a wide range of organic molecules, many of which have structures not known before. An example is a highly symmetrical molecule in the form of a cage, which Mehta has named Golcondane. This name was chosen by Mehta to commemorate the 400th anniversary of the city of Hyderabad, whose original name was Golconda.

Another of his achievements is the synthesis of a bowl-shaped hydrocarbon -- C21 -- that he has named Sumanene, a Sanskrit word for "flower". This is an important component of the fullerene molecule, C60, which has received a great deal of attention because of its properties as a superconductor.

Explains Mehta, "The synthesis of Sumanene is an important step towards the synthesis of C60 itself, one of the most challenging problems in synthetic organic chemistry today." On his table he displays a model of the fullerene molecule that he breaks up into two identical C21 fragments and one C18 fragment. "My approach is to synthesise these two components separately and then see if they can be joined together to yield C60," he says.

Mehta has also been involved in the synthesis of complex chemical substances that are found in plants. He has synthesised about 10 natural products, of which six were produced in the lab for the first time. These substances are important in medicine and their synthesis in the lab is useful because in many cases they cannot be obtained in sufficient amounts from natural sources.

Rao's work at IICT, on the other hand, is directed towards synthesising drugs to treat such diseases as AIDS, cancer, tuberculosis, diabetes and asthma.

"Many of the vital drugs marketed by foreign companies are too expensive for most patients in India," he says. "Much of my work is concerned with finding methods of preparing essential drugs indigenously."

Rao is presently engaged in the synthesis of cyclosporin, a drug that suppresses the immune response and thereby prevents transplanted organs and tissues from being rejected by the body. A year's supply of this drug, manufactured by the Swiss company Sandoz, costs an Indian patient Rs 50,000. This cost could be reduced by more than half once cyclosporin is made indigenously. Rao has taken an important step in this direction by synthesising an amino acid that imparts the immunosuppression property to cyclosporin.

Rao has also made headway in the synthesis of FK-506, a newly discovered antibiotic that has attracted worldwide attention because it was shown to be 100 times more active as an immunosuppressant than cyclosporin. The structure of this compound is extremely complex and synthesising it poses a challenge to organic chemists, explains Rao. "Ours was the only group outside the US to have succeeded in building the top and bottom fragments of FK-506 and we are actively pursuing its total synthesis," he says.

Earlier, Rao had synthesised the AIDS drug AZT, which is now being marketed by CIPLA, Bombay. He is also well known for his work on the development of drugs against cancer, especially Fredericamycin, an antibiotic with anti-tumor properties.

Rao is focussing his attention on modifying the molecular structure of known drugs. "By making small variations in the structure of known molecules, it is possible to enhance their activity and reduce their side-effects," he says.

Rao's expertise in drug development is also reflected in the funding that his group has received from multinational drug companies such as Smith Kline Beecham Pharmaceuticals Ltd and Parke-Davis, USA, for research that may lead to new drugs.

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