towards an integrated research policy in the area of drug discovery in the arab countries
DESCRIPTION
Towards an Integrated Research Policy in the Area of Drug Discovery in the Arab Countries Including mechanisms to better utilization of their terrestrial and marine wealth . Bassem El-Menshawi NEPAD Sci & Technol Regional Coordinator for Northern Africa, - PowerPoint PPT PresentationTRANSCRIPT
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Towards an Integrated Research Policy in the Area of Drug Discovery in the
Arab Countries
Including mechanisms to better utilization of their terrestrial and marine wealth.
Bassem El-Menshawi
NEPAD Sci & Technol Regional Coordinator for Northern Africa,
National Research Centre, Cairo, Egypt
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DRUG DISCOVERY
TYPES OF RESEARCH LABORATORIES NEEDED:
This depends on the therapeutic class
required
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DRUGS TO BE DISCOVEREDFOR EXAMPLE: IF PRIORITY GIVEN TO:
-ANTITUMORS,
-ANTICARCINOGENIC,
-IMMUNOMODULATORY,
-ANTIVIRAL AGENTS
A CELL CULTURE LAB IS NEEDED
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THE STATE OF THE ART OF DRUG DISCOVERY:
• THE USE OF IN VITRO BIOASSAYS
• THE USE OF CELL LINES
(e.g. HUMAN TUMOR CELL LINES)
ADVANTAGES AND DISADVANTAGES In-Vitro Bioassays-Rapid, less selective, but diagnostic, less expensive, -suitable for minute amounts of materials, -suitable for screening large number of samples in Drug Discovery programs. In-Vivo Bioassays More selective, expensive, mostly Time Consuming,Animal model, require large amounts of material,hardly could guide the fractionation of extracts or mixture of compounds.
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TYPES OF RESOURCES TO BE UTILIZED:
Natural Resources Line : - Plants - Microbes (bacteria, fungi) - Marine Organisms
Synthetic Line: - Novel Chemical Entities - Generics
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THE BASIC CHEMICAL LABS:
LAB FOR NATURAL PRODUCTS(Isolation of Natural Compounds)
LAB FOR SYNTHESIS
(Rational Pharmacological, &
Computer Aided Drug Design)
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IN ADDITION TO
- ANTI-VIRAL TESTING LAB
- PHARMACOLOGICAL PROFILE &
TOXICOLOGY LAB
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FOR BIOTECHNOLOGICAL PRODUCTS
A BIOTECH / MOLECULAR BIOLOGY
FOR DISCOVERY OF ANTIBIOTICS:
A MICROBIOLOGY / FERMENTATION LAB
FOR ANTI-SCHISTOSOMIASIS:
PARASITOLOGY LAB
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THERAPEUTIC NATURAL PRODUCTS
- ACTIVE COMPOUNDS
- ACTIVE EXTRACTS
- COMBINED ACTIVE EXTRACTS
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METHODS OF DRUG DISCOVERY FROM NATURAL PRODUCTS
How the Active Principle be identified ? -Phytochemical Approach -Bio-Activity Approach -High Throughput Screening -Computer Aided HPLC/MS
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EXISTING PROJECT MODEL:AT THE NATIONAL RESEARCH CENTRE, EGYPT
A SEARCH FOR
SCHISTOSOOMICIDAL, ANTITUMOR, ANTICARCINOGENIC,
IMMUNOMODULATORY,
AND ANTIVIRAL AGENTS
IN EGYPTIAN PLANTS
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• This is a drug discovery program conducted at NRC
• based on Egyptian plants,
• utilizes universally accepted protocols
for bioabioactivitctivity-guided fractionationy-guided fractionation
of plant extracts,
• and in-Vitro Bioassays.
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Under this project Egyptian plants
are Bio-assayed for specific
medicinal activities:
1. Schistosomicidal
2. Antitumor
3. Cancer chemopreventive
[anticarcinogenic]
4. Immunomodulating
5. Antiviral
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BIOACTIVITY APPROACH:
-Extracts are screened for a specific medicinal activity (an in-vitro bioassay).
-Only BioActive extracts are fractionated.
-Active fractions are further fractionated
to isolate the active compound(s) in pure form.
-Characterization of its structure.
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• Only Bio-Active Extracts are subjected to
Bioassay-Guided Fractionation, in 2
steps:
1. Initial Partitioning
2. Comprehensive Fractionation
for the isolation of their active
principles.
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EX-VIVO BIOASSAY
• In-Vivo / In-Vitro
• Used for assaying the activity of compounds isolated in limited amounts,
• untill additional materials could be obtained sufficient for in-vivo bioassy.
• It detects the effect of in-vivo absorption and metabolism on compounds that are active in-vitro.
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Active compounds isolated are then bioassayed in animal models
to confirm the bioactivity
and determine their therapeutic value and toxicity profiles.
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The overall accomplishments After 3 years of the project’s life are as follows:
1. Plant Collection
1625 plant samples collected(Corresponding to 958 species:534 wild, and 424 cultivatedspecies).
2. Preparation of Plant Extracts
1787 13501149
plant organs dried andpowderedalcoholic extracts preparedwater extracts prepared
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3. In-Vitro Bioassays
3.A. Schistosomicidal bioassay
17961196 600
extracts bioassayedalcoholicaqueous
3.B. Antitumor bioassay:
(i) Brine Shrimp Bioassay
21181268 850
extracts bioassayedalcoholicaqueous
(ii) Ehrlich Ascites Carcinoma
1447 951 496
extracts bioassayedalcoholicaqueous
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3.C. Anti-carcinogenic activity
Micronucleus bioassay Antioxidant prescreen
10
200
Extracts bioassayed Extracts bioassayed
3.D. Immunomodulatory activity Murine Lymphoprol- Iferative
153
Extracts bioassayed
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3.E. Antiviral Activity
Foot & Mouth Disease virus
259 Extracts bioassayed
Hepatitis-A virus 80 Extracts bioassayed
Herpes Simplex 372 Extracts bioassayed
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342
176
24 44
14
3 1
55
25
Extracts have been classified as “Promising Bioactive” in all the bioassayys. Are as follows:
lcoholic extracts possessed 100% activity at 100ppm as Schistosomicidals. alcoholic extract possessed 100% at 50ppm (Brine Shrimp). extracts gave 75% at 100 ppm as Antitumor (Ehrlich). Anticarcinogenic. Micronucleus: Activity is under investigation extracts with 90% activity (% of inhibitory activity of radicle production) at 25 μg / ml as Antioxidant. extracts showed activity as Immunosuppressant. extract showed acivity as immunostimulant
alcoholic extracts with activity higher than 80% at 30 and 40μg /ml (43 contain tannins, and 12 without tannins) as
water extracts with activity higher than 80% at 40 μg /ml as Antivirals.
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4. Initial Fractionation
157
30 27 20
80
50
22 14
5
9
“Most Active” plant extracts in the bioassays were selected for fractionation and
confirmatory testing. active in schistosomicidal bioassay active in the Brine Shrimp lethality bioassay active in the Ehrlich ascites carcinoma bioassay active in the antiviral bioassay (44 of them are of 2nd priority due to their tannin contents) Results: Out of the above 157 extracts were fractionated and bioassayed: active in the Schistosomicidal bioassay active in the Brine Shrimp Lethality bioassay active in the Ehrlich ascites carcinoma bioassay active in the antiviral activity against HSV type I
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5. Bioactivity–Guided Fractionation
5 Extracts of the above weresubjected to comprehensivefractionation (completed)
6. Structuredetermination
533
Compounds were isolatedof them were identifiedother compounds are inisolation steps.
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7. Bioassay In-Vivo 7 4
Extracts Fractions were tested in ex-vivo bioassay, prior to testing them in-vivo
8. Toxicity in Animals
25 Extracts were studied for their toxicity in animals.
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Patenting and Discoveries : Bioactive Compounds Under Patenting
Bioactive Extracts/Fractions under Patenting
4 Antitimors, and 1 schistosomicidal
157 In three bioactivities (Schistosomicides,
Antitumors, and antivirals.
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Conclusions
-Screening Large Number of Natural Species
-Using In Vitro Bioassays
-For 5-10 Medicinal Activities
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•Conclusions:
-Integrates Arab Natural wealth
-Optimizes Arab IPR
-Enhance the Invention in a
Strategic Area
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Conclusions
- 1-3 Central Joint Research Lab (under one strategy, one mechanism, one protocol, and one leader).- Nodes in each country- Joint Surveying of Biodiversity-Joint Ownership of Products- Networking
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Conclusions
- Arab Meeting for Strategic Planning of Drug Discovery
- Role of Bibliotheca Alexandrina
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ALL THE PRAISES AND
THANKS BE TO
ALLAH
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RESEARC TEAM
Prof. Dr. Bassem El-Menshawi NRC Principal Investigator
Prof. Dr. Fouad Youssif TBRI
Prof. Dr. Abdel-Monem Osman NCI/Cairo Univ.
Prof. Dr. Laila Emara NRC
Assoc. Prof. Dr. Mohamed Aly NRC
Prof. Dr. Karima Mahrous NRC
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•
• THIS PROJECT IS FUNDED BY THE ACADEMY OF SCIENTIFIC RESEARCH AND TECHNOLOGY, CAIRO, EGYPT, UNDER THE
PROGRAM OF BIOTECHNOLOGY 1998.