Central Drug Research Institute (CDRI) is one of the fourty laboratories under the Council of Scientific and Industrial Research, an autonomous registered society of the federal government. Though established in 1947, it was formally inaugurated on 17 th February 1951.
CDRI is an institute dedicated to drug research. It possesses state-of-art facilities and infrastructure. The institute is a multi-disciplinary research laboratory with seventeen research and development divisions, nine technical services/divisions, three national facilities, two on one field center

Dr. C. M. Gupta
Central Drug Research Institute
P.O. Box - 173, M.G. Marg
Lucknow - 226 001 U.P., India 
Phone: +91-522-2210932, 2223286 
Fax: +91-522-2223405, 2223938 
E-mail : info@cdriindia.org
Website : http://www.cdriindia.org

• Study on pathophysiology of diseases for identification of new molecular targets in order to develop novel approaches for chemical intervention and development of diagnostics or bioassays.
• Characterization of enzyme markers for drug resistant malaria parasite and specific genome sequences as new drug targets and exploit them as novel approaches in drug discovery .
• Novel drug design using classical and combinatorial approaches, molecular modeling and X-ray crystallography.
• Highthroughput screening, using molecular targets, for rapid screening of large number of molecules in a short time in order to discover effective and safer drugs.
• Studies on mycobacterial proteins and virulence genes and characterisation of novel antigens and drug targets; comparative proteomics of cell membranes and study of cytoskeleton of target organisms (M tuberculosis).
• Bio-assay guided isolation of active principles from terrestrial plants and marine flora and fauna and synthesis of combinatorial libraries of bioactive molecules.
• Isolation of microbial strains from soil samples and their testing for antimicrobial activity against pathogenic bacteria and fungi, cultivation of strains for the production of active metabolite and characterization of the active compound.
• Fermentation processes related with the development of drug, drug intermediates, enzymes, amino acids, biotransformation products, etc. are studied.
• Optimization of process variables/parameters at bench and pilot scale fermenters, down stream processing of different fermentation products and studies on immobilized bioreactor systems.
• PCR based diagnostics for infective diseases (tuberculosis).
• Molecular characterization of the enzyme heme oxygenase of Plasmodium falciparum and development of antisense oligonucleotides for chemotherapy
• Analysis of Plasmodium apicoplast genome replication
• Molecular detection of pathogenic organisms for malaria, leishmaniasis and filariasis
• Screening of synthetic and natural products for antituberculosis, antifungal and antibacterial activity
• Construction of mycobacterial vectors, novel antigens and drug targets; basic studies on virulence genes
• Microbial production of lipases and microbial transformation of steroidal and non- steroidal compounds
• Design and synthesis of oligopeptide with antiarrhythemic and antithrombin activity

Equipments and facilities: 

• Tissue and cell culture facility
• Facility for the synthesis of peptides and nucleic acids
• X-Ray crystallography facility
• HTS DNA sequencing by gel based method
• Flow cell cytometer
• Image analyzer
• Thermal cyclers
• DNA electrophoresis
• Gel documentation system etc.

Several new facilities have been created keeping in view paradigm shift in recent years in approaches in drug discovery and development.

1. Facilities for utilizing knowledge tools and technologies such as for studies in frontier areas, viz. proteomics, genomics and structural and molecular biology for rational drug design.

2. Proteomics: 2D Electrophoresis, Image acquisition and analysis, spot cutting and processing, peptide mass mapping through MALDI-MS, protein identification through genome database search.

3. Facilities for development of new leads through the use of robotic multiple organic synthesiser for construction of new chemical libraries of several thousand compounds.

4. High throughput screening facility for quick screening of large number of compounds; Robotic assisted High throughput Screening System (Beckman Coulter)

5. Structural and computation biology facility for discovery of new drug targets and their structural elucidation, besides predicting types of molecules around which to build combinatoriallibraries through virtual screening.

6. State-of-the-art electron microscopy facility comprising of analytical transmission and environmental scanning electron microscopes and ultra microtome for better understanding of the mechanism of action of candidate drugs at molecular level.

7. PC based 120 Kv Transmission Electron MicroscopeFEI-Philips (Tecnai-12);

   Environmental Scanning Electron Microscope FEI-Philips(XL-30);

   Ultracryomicrotome UCT Leica.

8. Confocal microscope for investigating mechanism of drug action.

9. Fermentation technology equipments: Autoclaves, shaker incubators, laboratory fermenters, centrifuge, extractors, dryer, ball mill, evaporator, etc.

10. Sophisticated Animal facility registered under CPCSEA, possesses facilities for SPF animals, genetically characterised animals and inbreeding of rhesus monkeys.

1. Computer Automated Semen Analyser (CASA)

2. Centrifugal Elutriation for Separation of specific germ cell types from testis

3. Microscope with phase, Fluoroscence and Photography System

4. Hereavs Centrifuge; Scintillation Counter

5. Computerized gel documentation system

6. Culture for chick and rat fetal bones and their surgical transfer preimplantation embryos in rodents

7. Thermal Cycler

Acquisition of these facilities is being complemented with adequate strengthening of expertise in these areas by induction of new staff and reorientation of existing scientists.

1. On Line:

   The center provides access to various Databases and Journals online (through dedicated leased line connectivity) as well as offline through CD-ROM. The Center provides online access through Internet to some subscribed sites like Sciencedirect, Scifinder STN (DIALOG).

    

2. Off Line:

   Comprehensive databases are also available offline on CD-ROM for MEDLINE, Biotechnology Abstract in the area of Drugs & Pharmaceuticals, Excerpta Medica, Biological Abstract, Current Contents, Popline, Chemical Abstract (One year old) and indigenously developed databases for Natural Products and Folklore.

1. Commercialized

2. Developed

Developed over 100 technologies for bulk drugs/drug intermediates/biological/fermentation products. Some important technologies are:

3. Being Developed

Are there any special facilities/services for commercialization of products?

1. Synthesis of Combinatorial Libraries for Identification of Bioactive Organic Molecules and Peptides

CDRI has procured two robotic multiple organic synthesizers (MOS) with the view to synthesize libraries of organic molecules using both solid and liquid phase methods. Synthetic combinatorial libraries (SCL) have a new dimension to drug discovery by allowing the rapid synthesis of a large number of novel chemical entities. The chemical diversity and the large number of compounds for each class of structures available in SCL formats increase the probability of identifying biologically active compounds with chemical characteristics that are different from those of existing biologically active compounds. These libraries can be used both for the purpose of lead optimization as well as for lead generation against various molecular target-based or whole cell assays available in the institute.

Several libraries of single compounds and of novel molecules and several mixture-based libraries of peptides have been synthesized and screened against various biological assays available in the institute. Some libraries have been found to exhibit high order of activity against M Tuberculosis and other parasitic infections.  

Small organic molecules comprising nitrogen heterocycles hold special place due to their broad range of biological activity. Synthesis of structurally diverse substituted pyrimidines on solid phase has been carried out in high yield with excellent purity. Synthetic routes for the solid phase synthesis of aryl/aryloxypropanolamines with three point diversity have also been optimized. The efficacy of synthetic routes have been established by synthesizing a small library of compounds which have been characterized using HPLC, NMR and ES-MS. The compounds were obtained in 75 to 85% yields with purities ranging from 75 to 93%. 

The value and impact of natural product like structures for the development of new drug candidates is very high. At CDRI several natural products with potent biological activity are available, which can be diversified using combinatorial approach with an objective to optimize their biological activity. Synthetic routes for bioactive triterpene derivatives derived from plants have been optimized using solid phase. The derivatives have been designed and synthesized in a manner so as to generate libraries with two point diversity. The compounds were obtained in more than 70 % yield and have been characterized using ES-MS and NMR. Efforts are in progress to generate libraries of these compounds in parallel format.

2. Facility in Structural Biology

The facility has been created for discovery of new drug targets and their structure elucidation besides producing ideal leads through virtual receptor screening. It covers facility for X-ray crystallography for both small and large molecules. X-ray diffraction studies will help in identification of molecules of biological, medicinal and structural importance obtained through synthesis/cloning and separation/purification for preparation of diffraction quality crystals, help collection of X-ray intensity data and atomic/molecular level structure determinations.

3. Facility in High Throughput Screening

The highthroughput screening (HTS) system installed aims to speed up the pace of drug discovery at CDRI. HTS enables rapid in vitro screening of drug candidates so as to select the promising ones for further development. The speed and precision is attained through computer- assisted robotics. Programmed assay procedures are allowed to run continuously and results are read using online

microplate readers.

 

Several HTS assays are under development within the institute. Some of the

selected assays for the moment are given below:

 

• Anti-tuberculosis activity: Inhibition of mycobacterial cell viability by monitoring the activity of a reporter gene (luciferase) or reduction of a fluorescent indicator dye (Alamar Blue).

• Anti-malaria activity: Inhibition of plasmodial cell viability by monitoring the activity of parasite lactate dehydrogenase as a reporter enzyme.

• Anti-Ieishmania activity: Inhibition of Leishmania promastigote viability by monitoring reduction of an indicator dye (MTT/ Alamar Blue).

• Anti-thrombin activity: Inhibition of thrombin activity by monitoring the rate of substrate consumption colorimetrically.

4. Electron Microscope:

A new state-of-the-art facility in the electron microscopy for biological sciences has been created. The facility comprise the following instruments.

 

(i) PC based (NT window) analytical transmission electron microscope (Philips Techai -12) incorporates the state-of-the-art in electron optics, complete digital control and has all peripherals fully embedded for routine operation using EDX, CCD camera and GATTAN cryo stage. It facilitates to acquire digital images using CCD camera and online image analysis using SIS software which can be stored in CDs. GATTAN cryo specimen stage also facilitates opportunity to examine cryo -fixed cells, virus and biomolecules in frozen state.

 

(ii) Environmental screening electron microscope (Philips) XL – 30 TMP ) is a versatile microscope that combines high vacuum and ESEM technologies in one unit. The SEM facilitate to obtain 3-D image of hydrated biological specimens in natural state using gaseous secondary electron detector (GSED) while maintaining high gas pressure in the specimen chamber. Resolution limit of the instrument at 30Kv is 3.5

nm in high vacuum mode and in 5 Torr ESEM mode and 25 nm at 1Kv. 

 

iii) Ultra cryomicrotome (LEICA Ultra cut UCT) allows preparation of ultra thin sections of plastic embedded specimens at room temperatures as well as facilitates to cut ultracryothin (70 nm) sections of frozen biological specimens. 

5. Animal Facility

            Laboratory animals comprising of 26 different strains of rodent species, including 8 inbred strains of mice, 3 inbred strains of rat, 2 inbred strains of hamster, 2 strains of lagomorphs are maintained for the purpose of biomedical research in CPCSEA registered research organization including Govt., Pvt., Pharmaceutical companies, universities etc. through out India. In addition to this, Rhesus monkeys are also bred in ECO-friendly and environmental controlled runs. This centre also possesses Specific Pathogen Free (SPF) conditions for rodents.

 

More than 15 Bio-chemical markers have been standardized for testing genetic purity homozygocity, hetrozyocity in these animal strains. In addition to this, bio-chemical markers are also used for diversity studies, strain identification as well as for improving breeding performances of some of the important strains of laboratory animals. A new strain of white hamster and hairless mouse has been developed in this facility using selective breeding of the specific mutation observed in the strains of golden hamster and Swiss mice respectively.

 

More than 16 cell lines derives from human as well as animals are maintained, kept preserved and supplied to various research organizations, including pharmaceuticals companies. This tissue culture unit is one of the active component of this facility for providing more alternatives to the animal usage for biomedical research.

 

Future programs of this centre aim at developing DNA micro-satellite markers for both disease diagnosis and strain characterization of laboratory animals. The programs on SPF, gnotobiotic and transgenic animal facility are also envisaged. Further extensive programs on ECO-friendly breeding and rehabilitation of rhesus

monkeys are also in process.

6. Development of a rapid PCR based assay for diagnosis of TB

            A rapid PCR based assay for diagnosis of tuberculosis (TB) has been developed by CDRI. This DNA based diagnostic assay consists of 12901 bp fragment of Mycobacterium tuberculosis, the causative agent of tuberculosis which is not present in other mycobacteria. The oligonucleotide primers were designed to amplify by PCR, a 791 bp fragment from M. tuberculosis present in clinical samples. The fragment can be amplified directly from clinical samples from TB patients and results can be reported within 24 hours as compared to 8 weeks by culture method.

 

The probe has been evaluated independently in three laboratories on coded sputum samples under the sponsorship of Department of Biotechnology (DBT) along with four other probes developed elsewhere in the country. After careful evaluation and discussion, it was recommended that "the assay was considered to be of

acceptable sensitivity as well as specificity for detection of M tuberculosis specific sequences and were considered to be suitable for use in sputum specimens". The probe and assay developed by CDRI has been used by Command Hospital and Sanjay Gandhi Post Graduate Institute of Medical Sciences located in Lucknow.

7. Fermentation Technology Facility

            The CDRI's strength in fermentation covers complete facilities for development of fermentation processes -optimization of process parameters and scaling up of bioprocesses to laboratory and pilot fermenter levels. Research programmes cover development of fermentation processes for drugs/drug intermediate, amino acids and enzymes; development of new antibiotics and modification of known antibiotics; microbial biotransformation, culture isolation, maintenance, improvement and development of new strains. Among important facilities available are: fermenters for 5, 10, 15, 20, 150 & 1500 L alongwith

downstream processing facilities such a centrifugation, extraction, concentration, drying, etc. Studies are carried out on various biotransformation processes at bench level in novel bioreactor systems using free as well as immobilized biocatalysts.

 

Microbes isolated from soil samples collected from selected places and evaluated for antifungal/antibacterial activities; active strains are isolated and cultivated. Facilities provide for downstream processing of active products, including their isolation and identification. The project drives strength from the fact that natural products continue to be a major source of structural diversity providing lead molecules with potential to show activity against a wide range of targets.

Type of Computer Networking (Yes / No): No LAN

7. Services Provided:

• Public Awareness

               Open days observed on National Science Day (28th February), CSIR Foundation Day (26 September) and other special occasions.

               Organise exhibitions on the occasion of national and international events.

• Educational/Human Resource Development

                Training to M. Tech., M.Sc. students from various institutions/training to industry sponsored personnel. 

• Major Events held in last five years:

1. Symposium on 'Bioprocessing and r-DNA Technology (27-28 March, 1998)

 

2. TCDC International Training Workshop on 'Emerging Trends in the Diagnosis of Infectious
    Diseases (7 December, 1998) 

 

3. 31st  Annual Conference of Indian Pharmacological Society (18-20 December, 1998)

 

4. Sixtyfifth Annual Meeting of Indian Academy of Sciences (29-31 October , 1999)

 

5. 4th National Conference of Indian Society of Chemists and Biologists (28-30 January,2000)

 

6. CDRI-Industry Meet "Pharma R&D in 21st  Century (16 February, 2000)

 

7. Mini Symposium on Structural Biology (19 February 2000)

 

8. Symposium on Current Status in Fertility Regulation (15-16 November, 2000)

 

9. National Symposium on Tropical Diseases (7-9 November, 2000)

 

10. CDRI Golden Jubilee celebrations (February 2001)

 

11. Mini Symposium on Structural Biology (19 February 2000)

12. Symposium on Current Status in Fertility Regulation (15-16 November, 2000)

13. National Symposium on Tropical Diseases (7-9 November, 2000)

14. CDRI Golden Jubilee celebrations (February 2001)

 

15. International Conference on "Current Trends in Drug Development Research" (11-15
      February,2001).

 

16. TDR/WHO Workshop on Good Laboratory Practice (GLP) (March 19-21,2001)

 

17. National Symposium on Chemical Sciences, Advancing Frontiers (June 03,2001)

 

18. Symposium on Natural Products in Health and Disease (11 October 2002)

• Events planned for next five years

            11 th BPCON conference (15-16 February, 2003)

8. Details of the Biotechnology Information Centre (if any) in the Organisation:

The center provides access to various Databases and Journals online (through dedicated leased line connectivity) as well as offline through CD-ROM. The Center provides online access through Internet to some subscribed sites like Sciencedirect, Scifinder STN (DIALOG).

Comprehensive databases are also available offline on CD-ROM for MEDLINE, Biotechnology Abstract in the area of Drugs & Pharmaceuticals, Excerpta Medica, Biological Abstract, Current Contents, Popline, Chemical Abstract (One year old) and indigenously developed databases for Natural Products and Folklore.

The Center has access to over 1200 journals and ten databases in the area of science and Biotechnological information. Subscribed journals are available as Full- Text Documents in PDF as well as HTML format. Bibliographic information is also available containing citations with abstract. The center also provides Internet facilities for Scientists, Research fellows, Technical and Administrative staff of this Institute.

9. Contact person for further enquiry:

Name:            Dr. Zaka Imam

Designation:    

Tel:                0522-

Fax:               0522-223405/223938

e-mail:            

1. Srivastava R., Deb D.K., Srivastava K.K., Locht C. and Srivastava B.S. (1998) Green fluoroscent protein as a reporter in rapid screening of antituberculosis compounds in vitro and in macrophages. Biochem. Biophys. Res. Commn. 253: 431-36
2. Singh N. and Rastogi A.K. (1999) Kinetoplast DNA minicircle of Leishmania donavani expresses a protein product. Biochem. Biophys. Acta 1444: 263-68
3. Srivastava K.K. and Verma P.K. (1999) A recombinant cellulolytic E. coli: Cloning of the cellulase gene and characterization of a bifunctional cellulase. Biotechnol. Lett. 21: 293-97

Products :

• Arteether
• Ablaquin
• Centchroman
• Gugulip
• Brahmi extract

Process technology for :

• Artemether
• Dextropropoxyphene-HCl
• Ephedrene

Dr. Zaka Imam
Deputy Director & Head,
Technical Information,
Industrial Liaison & Planning 
Central Drug Research Institute
P.O. Box - 173, M.G. Marg
Lucknow - 226 001 U.P., India 
Tel : +91-522-2223702
Fax : +91-522-2223405/2223938
E-mail : zaka_imam@yahoo.com
Website : http://www.cdriindia.org