Tag Archives: Drug development

Better Prescription

After open source software, it is now the turn of open source drug research. If this unique process can find a new anti-TB drug, it might well become the future of drug research. G.S. Mudur reports
In the temple town of Thanjavur, Aparna Venkatachalam, a final year engineering student, has turned into a foot soldier in a fresh scientific assault on the microbe that causes tuberculosis. After combing through some 200 research papers and spending dozens of hours searching online biological databases, she has assigned functions — biological tasks — to 60 proteins found in the TB microbe. She picked up a reward for her efforts last week — an Acer Netbook.

Venkatachalam is one of a group of 120 students and researchers scattered across India, Dubai, Japan and Germany, who have put together the most detailed map constructed so far to describe the biochemistry of a living organism. The 18-month science project, spearheaded by India’s Council of Scientific and Industrial Research (CSIR), is seeking new drugs against the TB microbe in a manner never attempted before.

“When you want to destroy an enemy, it’s good to identify vulnerabilities,” said Samir Brahmachari, director general of the CSIR. “This map will provide us unprecedented insights into the biochemistry of the TB micro-organism.”

The search for new drugs against TB is the first project of the CSIR’s Open Source Drug Discovery (OSDD) programme, a Rs 150 crore effort to solve complex problems by breaking them into smaller “work packets” open to virtually anyone across the scientific community to solve. The challenges are posed on the OSDD website, and researchers wishing to try and tackle them need only to register and join the effort.

An international consortium of scientists had sequenced the genome of the microbe Mycobacterium TB [MTB] nearly 12 years ago. And over the past decade, scientists have identified 3,998 genes, and assigned biological functions to all but nine of them.

The OSDD effort has now generated a map that places about 3,700 MTB genes and their protein products into a network of biochemical pathways. The network, a web of biochemical reactions, shows how these genes and proteins allow MTB to carry out its myriad life-cycle activities — from invading human cells to evading the human immune system to routine housekeeping.

“It’s a very big and a very complex circuit,” said Hiraoki Kitanu, director of the Systems Biology Institute in Japan, who leads a research team that has contributed significantly to the development of a computer-readable format to display models of biological processes, and who has joined the OSDD effort. “This is a new approach for drug discovery,” Kitanu said.

Scientists believe MTB is an appropriate organism to pit innovative ideas against. This killer microbe claims about 1,000 lives across India each day. The four best anti-TB drugs that make up the first line of therapy were developed in the 1950s and 1960s. Secondary drugs are toxic and expensive. There are now drug-resistant versions of MTB, which pose a new challenge. While clinical trials are under way, a new drug is not expected to be ready for use until 2012.

All previous efforts at finding drugs to fight MTB involved a laborious trial-and-error method in which researchers exposed the organism to compounds and picked the ones that appeared most effective in killing bacteria or suppressing their growth. Researchers believe that the map of biochemical pathways will now allow them to choose specific regions of the pathway as targets for future drugs. “Instead of shooting in the dark, we’ll be searching for targets in a rational way,” said Anshu Bharadwaj, a scientist at the Institute of Genomics and Integrative Biology, New Delhi, who, among other roles, also assigns work packets to OSDD researchers.

Some 800 researchers — most of them students — joined the effort, but only some 120 who succeeded in assigning functions to at least 40 genes — Venkatachalam among them — were picked to receive the reward. One of them was a homemaker from Dubai who had used her skills in bioinformatics to help build the pathways map. All those who won a reward, however, did not attend the meeting in Delhi — a software engineer from Germany told the OSDD that he doesn’t travel as he is wheelchair bound.

Venkatachalam, a bioinformatics student at SASTRA University in Thanjavur, and her colleague Ahalyaa Subramanian scanned published scientific literature to tell the stories of 60 MTB genes. In all, Brahmachari estimates, the consortium of researchers scanned at least 12,000 research papers on TB and compiled the information in a standardised format to build the map.

Some biologists caution people not to expect a new drug too soon. “I’m very optimistic this is going to have an impact,” said Richard Jefferson, a molecular biologist based in Australia and chief executive officer of Cambia, a non-profit institute seeking to promote innovation. “But it’s important we do not expect too much too soon. It’s going to be a long fight,” Jefferson said at the OSDD meeting last week.

In the drug discovery process, scientists will have to look for “vulnerabilities” in MTB pathways that can be exploited to design a new drug. Researchers say that one of the biggest challenges will be to find compounds that act exclusively on MTB. “We’ll need to find a vulnerability exclusive to MTB that leaves the human system alone,” said Bharadwaj.

Brahmachari himself has ventured to suggest that the effort could lead to a new candidate drug ready for clinical trials within two years. If that happens, said Brahmachari, the OSDD will invite five drug companies to invest four per cent of drug development costs, while the CSIR will provide the remainder 80 per cent. Each company would then get an opportunity to produce inexpensive generic versions of the drug.

If the OSDD does indeed deliver a new and effective drug for TB, it might trigger a paradigm change in drug research.

Source: The Telegraph (Kolkata, India)

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Daruharidra (Berberis aristata)

Botanical Name : Berberis aristata
Family: Berberidaceae
Kingdom:
Plantae
Order:
Ranunculales
Genus:
Berberis
Species:
B. aristata

Common name: Chitra
Other Common Names:   Darlahad [H], Hint Amberparisi [E], Indian Lycium [E], Nepal Barberry [H], Ophthalmic Barberry [H] (From various places around the Web, may not be 100% correct.) Barberry, Nepal
Vernacular Name: Sans; Daruharidra; Hind: Darhald; Eng : Indian barberry
Synonyms: Berberis coriaria (Lindl.), Berberis chitria (Hort.)

Sanskrit Synonyms:
Darunisha, Peeta, Daruharidra, Darvi, Peetadru, Peetachandana, Hemakanti, Kashta Rajani, Peetaka, Peetahva, Hemakanta,Hemavarnavati, – All these synonyms explain about turmeric-like yellow coloured stem.
Katankati, Katankateri, Parjanya, Pachampacha, Kusumbhaka,
Habitat :E. Asia – Himalayas in Nepal.(Shrubberies to 3500 metres)Woodland, Dappled Shade, Shady Edge.

Description:

Daruharidra is an evergreen erect spiny shrub, ranging between 2 and 3 meters in height. It is a woody plant, with bark that appears yellow to brown from the outside and deep yellow from the inside. The bark is covered with three-branched thorns, which are modified leaves, and can be removed by hand in longitudinal strips. The leaves are arranged in tufts of 5-8 and are approximately 4.9 centimeters long and 1.8 centimeters broad. The leaves are deep green on the dorsal surface and light green on the ventral surface. The leaves are simple with pinnate venation. The leaves are leathery in texture and are toothed, with several to many small indentations along the margin of the leaf.
It is a woody plant, with bark that appears yellow to brown from the outside and deep yellow from the inside. The bark is covered with three-branched thorns, which are modified leaves, and can be removed by hand in longitudinal strips. The leaves are arranged in tufts of 5-8 and are approximately 4.9 centimeters long and 1.8 centimeters broad. The leaves are deep green on the dorsal surface and light green on the ventral surface. The leaves are simple with pinnate venation. The leaves are leathery in texture and are toothed, with several to many small indentations along the margin of the leaf.

The flowering season begins in mid-March and lasts throughout the month of April. The yellow flowers that develop are complete and hermaphroditic. The average diameter of a fully opened flower is 12.5 millimeters. The flowers form a racemose inflorescence, with 11 to 16 flowers per raceme, arranged along a central stem. The flower is polysepalous, with 3 large and 3 small sepals, and polypetalous, with 6 petals in total. The male reproductive structure, the androecium, is polyandrous and contains 6 stamens, 5 to 6 millimeters long. There is one female reproductive structure, the gynoecium, which is 4 to 5 millimeters long and is composed of a short style and a broad stigma. The plant produces bunches of succulent, acidic, edible berries that are bright red in color and have medicinal properties. The fruits start ripening from the second week of May and continue to do so throughout June. The berries are approximately 7 millimeters long, 4 millimeters in diameter and weigh about 227 milligrams.

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Cultivation :   Prefers a warm moist loamy soil and light shade but it is by no means fastidious, succeeding in thin, dry and shallow soils. Grows well in heavy clay soils. The plant prefers light (sandy), medium (loamy) and heavy (clay) soils and can grow in heavy clay and nutritionally poor soils. The plant prefers acid, neutral and basic (alkaline) soils. It can grow in semi-shade (light woodland) or no shade. It requires dry or moist soil. Plants are very hardy, they survived the severe winters of 1986-1987 without problems in most areas of Britain.

Plants can be pruned back quite severely and resprout well from the base. The fruits are sometimes sold in local markets in India. Hybridizes freely with other members of this genus. Most plants cultivated under this name are B. chitria., B. coriaria., B. glaucocarpa. and, more commonly, B. floribunda.

Propagation:  Seed – best sown as soon as it is ripe in a cold frame, it should germinate in late winter or early spring.  Seed from over-ripe fruit will take longer to germinate. Stored seed may require cold stratification and should be sown in a cold frame as early in the year as possible. When they are large enough to handle, prick the seedlings out into individual pots and grow them on in the greenhouse or cold frame for at least their first winter. Once they are at least 20cm tall, plant them out into their permanent positions in late spring or early summer, after the last expected frosts. The seedlings are subject to damping off, so be careful not to overwater them and keep them well ventilated.

Cuttings of half-ripe wood, July/August in a frame. Very difficult, if not impossible. Cuttings of mature wood of the current season’s growth, preferably with a heel, October/November in a frame . Very difficult, if not impossible.

Edible Uses:  Fruit – raw or cooked. A well-flavoured fruit, it has a sweet taste with a blend of acid, though there is a slight bitterness caused by the seeds. The fruit is much liked by children. It is dried and used like raisins in India. The fruit contains about 2.3% protein, 12% sugars, 2% ash, 0.6% tannin, 0.4% pectin. There is 4.6mg vitamin C per 100ml of juice.The fruit is about 7mm x 4mm – it can be up to 10mm long. Plants in the wild yield about 650g of fruit in 4 pickings.

Flower buds – added to sauces.

Composition:  Fruit (Fresh weight) :In grammes per 100g weight of food:Protein: 2.3 Carbohydrate: 12 Ash: 2

Medicinal Uses:  Alterative; Antibacterial; Antiperiodic; Bitter; Cancer; Deobstruent; Diaphoretic; Laxative; Ophthalmic; Tonic.

The dried stem, root bark and wood are alterative, antiperiodic, deobstruent, diaphoretic, laxative, ophthalmic and tonic (bitter). An infusion is used in the treatment of malaria, eye complaints, skin diseases, menorrhagia, diarrhoea and jaundice.

Berberine, universally present in rhizomes of Berberis species, has marked antibacterial effects. Since it is not appreciably absorbed by the body, it is used orally in the treatment of various enteric infections, especially bacterial dysentery]. It should not be used with Glycyrrhiza species (Liquorice) because this nullifies the effects of the berberine. Berberine has also shown antitumour activity.

As per Ayurveda:
It is tikta, katu, ushnaveerya; applied in the treatment of septic wounds and polyuria, pruritus, erysipelas and diseases of skin, eye and ear; antidotal

 Therapeutic uses: Paste of root-bark finds external application for healing ulcers. Extract prepared from root-bark is used as a local application in affected parts of the eyelids and in chronic ophthalmia.The tincture of the root is used against intermittent fever and considered to be advantageous over quinine and cinchona since it does not produce deafness or cardiac depression.

The decoction is particularly useful in the enlargement of liver and spleen associated with malarial fever. It is also used for fever accompanied by diarrhoea. Root combined with opium, rocksalt and alum is considered to be an useful anti-inflammatory agent.

In bleeding piles, application of powdered root mixed with butter is beneficial. “Rasauf’ of the rootprepared withis found useful in stomatitis and leucorrhoea.

Decoction of stem mixed with that of curcuma longa is recommended in’gonorrhoea.

Bark juice is useful in jaundice.

Fruits are edible and prescribed as a mild laxative for children.

 Other Uses:A yellow dye is obtained from the root and the stem. An important source of dyestuff and tannin, it is perhaps one of the best tannin dyes available in India. The wood is used as a fuel.

Disclaimer:The information presented herein is intended for educational purposes only. Individual results may vary, and before using any supplements, it is always advisable to consult with your own health care provider.

 

Resources:
http://www.ibiblio.org/pfaf/cgi-bin/arr_html?Berberis+aristata
http://www.ayurvedakalamandiram.com/herbs.htm#bringraj
http://www.motherherbs.com/berberis-aristata.html
http://www.ayurgold.com/clinical_studies/indian_barberry

http://en.wikipedia.org/wiki/Berberis_aristata

 

 

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