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

TYPES OF RESEARCH LABORATORIES NEEDED: DRUG DISCOVERY TYPES OF RESEARCH LABORATORIES NEEDED: This depends on the therapeutic class required

FOR EXAMPLE: IF PRIORITY GIVEN TO: DRUGS TO BE DISCOVERED FOR EXAMPLE: IF PRIORITY GIVEN TO: -ANTITUMORS, -ANTICARCINOGENIC, -IMMUNOMODULATORY, -ANTIVIRAL AGENTS A CELL CULTURE LAB IS NEEDED

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.

TYPES OF RESOURCES TO BE UTILIZED: Natural Resources Line : - Plants - Microbes (bacteria, fungi) - Marine Organisms Synthetic Line: - Novel Chemical Entities - Generics

LAB FOR NATURAL PRODUCTS THE BASIC CHEMICAL LABS: LAB FOR NATURAL PRODUCTS (Isolation of Natural Compounds) LAB FOR SYNTHESIS (Rational Pharmacological, & Computer Aided Drug Design)

IN ADDITION TO - ANTI-VIRAL TESTING LAB - PHARMACOLOGICAL PROFILE & TOXICOLOGY LAB

FOR BIOTECHNOLOGICAL PRODUCTS A BIOTECH / MOLECULAR BIOLOGY FOR DISCOVERY OF ANTIBIOTICS: A MICROBIOLOGY / FERMENTATION LAB FOR ANTI-SCHISTOSOMIASIS: PARASITOLOGY LAB

THERAPEUTIC NATURAL PRODUCTS - ACTIVE COMPOUNDS - ACTIVE EXTRACTS - COMBINED ACTIVE EXTRACTS

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

EXISTING PROJECT MODEL: AT THE NATIONAL RESEARCH CENTRE, EGYPT A SEARCH FOR SCHISTOSOOMICIDAL, ANTITUMOR, ANTICARCINOGENIC, IMMUNOMODULATORY, AND ANTIVIRAL AGENTS IN EGYPTIAN PLANTS

This is a drug discovery program conducted at NRC based on Egyptian plants, utilizes universally accepted protocols for bioactivity-guided fractionation of plant extracts, and in-Vitro Bioassays.

Under this project Egyptian plants are Bio-assayed for specific medicinal activities: Schistosomicidal Antitumor Cancer chemopreventive [anticarcinogenic] Immunomodulating Antiviral

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.

Only Bio-Active Extracts are subjected to Bioassay-Guided Fractionation, in 2 steps: Initial Partitioning Comprehensive Fractionation for the isolation of their active principles.

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.

Active compounds isolated are then bioassayed in animal models to confirm the bioactivity and determine their therapeutic value and toxicity profiles.

The overall accomplishments After 3 years of the project’s life are as follows:

Conclusions -Screening Large Number of Natural Species -Using In Vitro Bioassays -For 5-10 Medicinal Activities

Conclusions: -Integrates Arab Natural wealth -Optimizes Arab IPR -Enhance the Invention in a Strategic Area

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

Conclusions - Arab Meeting for Strategic Planning of Drug Discovery - Role of Bibliotheca Alexandrina

ALL THE PRAISES AND THANKS BE TO ALLAH

THIS PROJECT IS FUNDED BY THE ACADEMY OF SCIENTIFIC RESEARCH AND TECHNOLOGY, CAIRO, EGYPT, UNDER THE PROGRAM OF BIOTECHNOLOGY 1998.