Building R&D Capacity in S&T-lagging Countries for Discovery and Development of New Drugs from Regional Biota

1st DRDC Conference, BUHS, Dhaka, October 3-6, 2015

(DRAFT) Report on Scientific Program and Recommendations

Prepared by Ahmed A Azad (aaazad1945@gmail.com)

1. Introduction:

The first international conference on “Drug Discovery and Development Research in Developing Countries” (DRDC-1) was held on October 3-6, 2015 in Dhaka, Bangladesh. It was organised by the Bangladesh University of Health Sciences (BUHS), a new private institution that aims to evolve into a research university of international standing with a major focus on clinical translational research with all the required constituent academic disciplines. The conference was very generously sponsored by the International Centre for Genetic Engineering and Biotechnology (Trieste, Italy) and Incepta Pharmaceuticals Ltd. (Bangladesh). Other major sponsors included The World Academy of Sciences (TWAS) and the Ministerial Standing Committee on Scientific and Technological Cooperation of the OIC (COMSTECH). The conference was held within the still under-construction BUHS campus in the recently completed Ibrahim Lecture Theatre, named after the visionary Prof Ibrahim who built many medical institutions in Bangladesh including BIRDEM and whose philosophy of making medicine readily affordable to disadvantaged populations who need it most pervades the thinking of the newly established BUHS. The number of total participants from academia, industry and government was in excess of 450.Foreign participants came from India, Pakistan, Turkey, Argentina, USA, UK, Singapore, Japan, Switzerland and South Korea.Out of the 48 invited speakers,26 were from overseas and of these 13 were young expatriate scientists of Bangladeshi origin.

1. Conference Theme:

The theme of the conference was“Building R&D Capacity in S&T-lagging Countries for Discovery and Development of New Drugs from Regional Biota”.Till about the mid-19th century almost all medicines were herbal remedies. In more recent times some of the best known modern medicines such as aspirin, morphine, digitalis, penicillin and taxol are derived from living organisms. The developing worldis endowed with a very rich biodiversity with unique hot spots of flora and fauna in different regions, and a wide and varying wealth of indigenous knowledge systems. This coupled with modern technology could lead to the discovery and development of new medicines for the diseases afflicting the developing countries. Translation of discovery into products is severely affected by the R&D chasm that exists in almost all S&T-lagging countries of the developing world, and hence the need to develop the required expertise and capacity in modern technologies.The consistently high attendance throughout the conference showed that the thematic topics were both interesting and relevant.

Even today discovery and development of natural product-based medicines remains highly relevant when the pipeline of new conventional medicines has almost dried up.   On the third day of the conference the recipients of Nobel Prizes for Medicine in 2015 were announced. These awards reinforced the importance and topicality of the conference theme. It was no accident that the Nobel Prize for Medicine this year was awarded to three scientists for the development of drugs from the Biota (flora, fauna and living organisms). Dr TuYouyouof China received her award for the development of a new anti-malarial drug, artemisinin, from a medicinal plant that has been used in China for over 2000 years. In the last 15 years artemisinin has halved the number of deaths inflicted by malaria. Dr Satoshi Omura of Japan and Dr William Campbell from USA received their award for the discovery and development of avermectin from Streptomyces bacteria. Avermectin kills parasitic worms that cause filariasis and river blindness. A newer version called ivermectin is listed on the WHO’s list of Essential Medicines. It should be stressed that neither of the two parasitic drugs are crude natural product extracts but modern medicines developed through multidisciplinary research and use of new technologies. This was also emphasised in the two inaugural lectures on the first day of the conference.

1. Inaugural Lectures:(October 3)

The two Inaugural Lectures, an Introductory Lecture and a State-of-Art Lecture,helped set the tone and agenda for the rest of the conference proceedings.

Introductory Lecture:

Prof Ahmed Azad (BUHS) demonstrated, with examples from research in his own laboratory, how conventional natural products-based drug research and modern molecular biosciences can have a very beneficial symbiotic relationship. He emphasised the use of disease-specific bioassays based on disease-specific molecular targets to discover lead compounds and to monitor efficacy through the development process, and also the use of modern technologies and appropriate animal models to optimise the lead compounds intocandidate drugs. In S&T-lagging low and middle income countries some of the required technologies can be accessed through focused collaboration between research groups possessing complementary expertise and facilities.

State-of-Art Lecture:

Prof M Iqbal Choudhary is the Director of Karachi University’s International Centre for Chemical and Biological Sciences (ICCBS), a centre that possesses many of the modern technologies required for drug discovery and pre-clinical development that are not readily available in the S&T-lagging countries. He described the use of cutting edge technologies at the interface of chemistry and biology in discovering from nature anti-infective agents against multiple drug resistant (MDR) bacteria, helper molecules that enhance activity of existing antibiotics, and potential antiepileptic medicines. These discoveries would not have been possible without using an interdisciplinary approach.

1. Symposium “From Bench to the Bedside”: (October 3-5)

The main component of the conference was the Symposium that was held over three days (Oct 3-5) and spanned the entire spectrum of multidisciplinary drug discovery and development research, where international and local experts in different scientific, technological and commercial disciplines covered the range of expertise and technologies required for the production of modern medicines starting from the discovery of new leads to regulatory requirements and manufacturing. The symposium lectures also allowed an assessment of what expertise and facilities were already available and what new capacity needed to be developed for the production and commercialisation of new medicines in Bangladesh and other developing countries. The following is a summary of the symposium proceedings:

Symposium Session 1 “Biota as a source of new medicines”:(October 3)

• Dr BholaNathDhawan (Emeritus Scientist, Central Drug Research Institute, Lucknow, India) described the range of medicinal plants, bioassays and other biological resources held at CDRI, the results of extensive bioprospecting, and some of the natural products-based drugs developed in his institute.
• Prof MunirOzturk (Emeritus Professor of Botany, Ege University, Izmir, Turkey) covered the ethnobiological and ethnopharmacological knowledge of traditional medicines used in West Asia, East Mediterranian countries and North Africa.
• Dr Julian Ferreras (Universidad National de Misiones, Misiones, Argentina) described the activities of his group in exploring natural products isolated from Actinomycetes bacteria in the only surviving forests in the Atlantic belt of northern Argentina. Because of the remoteness and scientific backwardness of Misiones province, Dr Ferreras is very keen to establish collaborations with S&T-lagging developing countries.
• Prof TohruMitsunaga (Natural Products Chemistry Lab, Gifu University, Japan) talked about his work with Indonesian collaborators in developing quercetin derivatives from traditional medicines that have an effect on melanogenesis stimulation of melanoma cells.

Symposium Session 2 “Structural insights into new therapeutic lead compounds”:(October 3)

• Prof Chitra Mandal (CSIR-Indian Institute of Chemical Biology, Kolkata, India) described a non-toxic carbazole alkaloid isolated from an edible plant that has shown great potential in vitro and in xenografic mouse model against a number of different cancers. The plant extract is also active and could be used as a nutriceutical.
• Prof Bina Siddiqui (ICCBS, Karachi University, Pakistan) showed how a number of lead compounds from natural products were chemically modified to greatly enhance their efficacy to qualify as candidate drugs against various diseases.
• Dr MontasirElahi (Jutendo University, Tokyo, Japan) presented a paper on the structural and thermodynamic analysis of the envelope protein of dengue virus that provide insights into the serospecificity and evolution of the virus.

Symposium Session 3 “Disease-specific molecular targets”:(October 4)

• Emeritus Prof Samir Bhattacharaya (School of