The 4th Euro-Mediterranean Conference of Natural Products and Drug Discovery:Back to Mother Nature(BioNat-IV),Cairo/Sharm El-Sheikh,Egypt,March 3–7,2015

Ashraf A.Khalil*,Marwa M.S.Dia,Kamal D.Moudgil

aDepartment of Protein Technology,City of Scientifc Research and Technological Applications,Borg Elarab, Alexandria,Egypt

bMolecular Drug Evaluation Department,National Organization for Drug Control and Research(NODCAR), Giza 12553,Egypt

cUniversity of Maryland School of Medicine,Baltimore,MD 21201,USA

The 4th Euro-Mediterranean Conference of Natural Products and Drug Discovery:Back to Mother Nature(BioNat-IV),Cairo/Sharm El-Sheikh,Egypt,March 3–7,2015

Ashraf A.Khalila,*,Marwa M.S.Diabb,Kamal D.Moudgilc

aDepartment of Protein Technology,City of Scientifc Research and Technological Applications,Borg Elarab, Alexandria,Egypt

bMolecular Drug Evaluation Department,National Organization for Drug Control and Research(NODCAR), Giza 12553,Egypt

cUniversity of Maryland School of Medicine,Baltimore,MD 21201,USA

A R T I C L EI N F O

Article history:

Available online 10 February 2016

BioNat

Natural products

Drug discovery

Mother Nature

Cooperation

The 4th Euro-Mediterranean Conference of Natural Products and Drug Discovery:Back to Mother Nature(BioNat-IV)was recently(from March 3rd through 7th,2015)convened in Cairo and Sharm El-Sheikh along the Red Sea coast of Egypt.Overall,the meeting provided a platform for scientists from different nations to discuss emerging ideas that focused on cell signaling in cancer;the pathogenesis of autoimmune diseases;the identifcation and use of natural products as well as novel drug delivery approaches for the treatment of cancer, arthritis,diabetes,tuberculosis,fungal infection,etc.;and untapped or unconventional sources for natural products.This fourth in a row conference tried to bridge the gap not only between basic research and clinical applications,but also between developed nations and developing countries.With the continuing success of these past meetings,the ffth Euro-Mediterranean Conference of Natural Products and Drug Discovery(BioNat-V)is slated to be in February 2017.

?2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical

University.This is an open access article under the CC BY-NC-ND license(http:// creativecommons.org/licenses/by-nc-nd/4.0/).

A natural product is a substance or chemical compound produced by a living organism that is found in nature.In the broadest sense,natural products include any substance produced by life.Natural products can also be replicated by chemical synthesis(both semisynthesis and total synthesis), and such undertakings have played a central role in the development of the feld of organic chemistry by taking on challenging synthetic targets.The term natural product has also been embraced for commercial purposes to refer to cosmetics,dietary supplements,and foods produced from natural sources without added artifcial ingredients.Within the feld of organic chemistry,the defnition of natural products is usuallyrestricted to purifed organic compounds isolated from natural sources that are produced via the pathways of primary or secondary metabolism.

Withinthefeldofmedicinalchemistry,thedefnitionisoften further restricted to secondary metabolites.Secondary metabolites are not essential for survival,but nevertheless provide the organisms that produce them with an evolutionary advantage.Many secondary metabolites are cytotoxic and have beenselectedandoptimizedthroughevolutionforuseas“chemical warfare”agents against prey,predators,and competing organisms.Natural products may possess pharmacological or biological activity that can be of therapeutic beneft in treatingdiseases.Assuch,naturalproductsaretheactivecomponents not only of most traditional medicines but also many modern medicines.Furthermore,because the structural diversity of natural products exceeds that readily achievable by chemical synthesis,and synthetic analogs of natural products can be prepared with improved potency and safety,natural products are often used as starting points for drug discovery.

Mixtures of plant-derived products are known as botanicals,and the term is defned by the United States(US)Food and Drug Administration(FDA)to describe fnished,labeled products that contain vegetable matter as ingredients,which can include plant materials,algae,macroscopic fungi,and combinations thereof[1].They can fall under the classifcation of a food(including a dietary supplement),a drug(including a biological drug),a medical device,or a cosmetic[1].The vast majority of plant-derived treatments are based on synthetic, semisynthetic,or otherwise highly purifed or chemically modifed drugs[1,2].According to the most recent report by BCC Research,the global plant-derived drug market was valued at US$22.1 billion in 2012,and sales are projected to grow to US$ 26.6 billion by 2017 at a compound annual growth rate(CAGR) of 3.8%[3].

Specifcally for life,health-driven research is an ideal objective to aim for.With this in mind,in 2011 fve Egyptian scientists from the City of Scientifc Research,Egypt,who possessed administrative skills,professional experience,research capabilities and scientifc relations/collaborations at local,regional(Arab)and international levels,decided to form the Euro-MediterraneanAssociation of Life Sciences(EMALS).The primary aims of EMALS were to contribute effectively to the international and national programs of scientifc research development, along with providing strategic services that affect the lives of scientists,researchers and their assistants,develop their professional and research competence,and raise the awareness of various segments of the society for natural products research and the use of these products for health care.Another main goal of this Association was to biannually organize a conference series in the Euro-Mediterranean area and invite the leaders from all over the world to discuss latest developments in life sciences,drug discovery and cancer research and other major diseases.Special emphasis and encouragement are provided to students,and trainees in Egypt and Euro-Mediterranean are to attend these meetings and to network with the leaders in their felds.

The purposes of the series of Euro-Mediterranean Conferences of Natural Products and Drug Discovery(BioNat)are to promote discussion and interaction among academic researchers,practitioners,and other professionals in the feld of natural products(metabolic networks,vitamins,carotenoids,favonoids,anti-nutrients,toxins,products of plant-associated microorganismsandbioactiveproteins).Attentionisalsodevoted toherbalmedicine,plant-deriveddrugs,phytopharmaceuticals, synthetic drugs,ethnopharmacology,biodiversity,as well as research strategies and legislations concerning natural productsresearch.Ultimately,thisseriesofconferenceswillovercome the challenges of drug discovery and drug delivery in a completely new way.BioNat hopes to help delegates convert these expensive,challenging and ineffcient processes into more accessible and affordable ones.

Planned open panel discussions and breakout sessions on key thematic areas are effective in energizing the participants in defning the drug discovery and development landscape.Several eminent scientists are expected to continue to attend these conferences,and this will defnitely contribute to advancing the scientifc knowledge regarding natural products.Beside our normal scientifc events,attendees have access to a variety of activities covering a large range of interests.

The frst such conference(BioNat-I)was conducted in the city of Cairo under the title Plant Natural Products from Biodiversity to Bioindustry from 8 to 10 December 2009.The themes of the frst meeting were(1)Plant Natural Products as Health Promoters and Food Additives;(2)Plant Biotechnology;(3)Plant Biodiversity,Protection and Conservation;(4)Plant Biodiversity&Chemical Ecology;(5)PlantToxins;(6)Evaluation of Plant Antioxidant Activities;and(7)Novel Elicitation Strategies&Enhancing Secondary Metabolite Production in Plants.This conference was inaugurated by the then President of the Egyptian Academy of Scientifc Research,Prof Mahmoud Saker.

The second international conference(BioNat-II)was conducted in the city ofAlexandria under the title Natural Products from Biodiversity to Bioindustry from 11 to 13 December 2011. The themes of the second meeting were:(1)Biotechnology, Pharmacology,and Toxicology;(2)Biological Actions;(3)Phytochemistry;(4)Formulations,Applications,Folklore,and Standardizations;(5)Plant-associated Microorganisms;and(6) Biodiversity and Conservations.This conference was inaugurated by the Governor ofAlexandria,the President ofAlexandria University and the Director of City of Scientifc Research.

The third international conference(BioNat-III)was conducted in the city of Cairo under the title Natural Products from Biotechnology to NanoMedicine from 4 to 7 January 2013.The topics covered in BioNat-III were(1)Stability and Effcacy of Natural Products;(2)Biotechnology and Molecular Biology;(3) ModeofActionofNaturalProducts;(4)Pharmacogenomics,Pharmacodynamics and Pharmacokinetics;(5)Nanoformulations, Nanoparticle Delivery and Nanotoxicology;(6)Pharmacology, Toxicology and BiologicalActions;and(7)RiskAssessment,Formulations,Applications&Standardizations.

The fourth international conference titled Natural Products and Drug Discovery was convened in Sharm El-Sheikh, March 3–7,2015.Long before the frst foreign tourists dived beneath Sharm el Sheikh’s crystal blue waters,this popular holiday destination was one of Egypt’s most signifcant ports. Located at the southern tip of the Sinai Peninsula,where the Red Sea meets the Gulf of Suez and the Gulf of Aqaba,Sharm el Sheikh has grown from a sleepy fshing village where 100 Bedouins lived just 40 years ago,into a major touristic hotspotand resort city in Egypt.Sharm el Sheikh has and continues to be called the“City of Peace,”referring to the large number of international peace conferences that have been held there. The most historical chapter of Sharm el Sheikh is said to have taken place in Jabal Musa(Mount Sinai),where,in Biblical times, Moses is believed to have climbed the mountain and received two tablets upon which the Ten Commandments were inscribed.Another important Biblical landmark situated near Sharm el Sheikh is St.Catherine’s Monastery,which dates all the way back to the 4th century BC and is widely acknowledged as being the site of the Burning Bush.

About 150 scientists from more than 15 nations gathered in the City of Peace to discuss natural products and drug discovery.During recent years,it has been recognized that identifcation of pathways that lead to the maintenance,survival,and/or proliferation of tumor tissue is needed to understand the pathophysiology of the disease,and importantly to identify druggable targets based on this pathophysiology. Drugs,such as Gleevec,which targets the biology of the disease, has become the poster child of how cancer could be treated, controlled,or cured.The objective of the 3-day conference (BioNat-IV)was to bring together laboratory and clinical scientists from developed and developing nations to share current knowledge and future strategies for drug discovery and to enlighten the chemistry of natural products.The format of the meeting was the daily main conference,parallel mini symposia,and poster sessions.

Prof.Dr.Ahmad M H Shaban,the vice president of the National Research Center(NRC),inaugurated the meeting in Cairo and emphasized the importance of research in natural products and medicinal plants,particularly for controlling cancer.Prof Dr.Ashraf Khalil(City of Scientifc Research,Borg Elarab,Egypt)chaired the frst session on Natural and Chemical Prevention of Cancer.Dr.Hassan Mukhtar(Wisconsin University)set the scientifc stage with his keynote speech that focused on his journey of targeted cancer therapy with nanoencapsulation of natural products.He reviewed 25 years of molecular medicine that evolved from oncogenomics.He has been instrumental in developing novel targeted therapeutics.His presentation also emphasized that while targets could be identifed and specifc drugs could be developed,in many cases resistance develops to the therapy,which poses new challenges.In another keynote lecture,Dr.Kamal D.Moudgil (University of Maryland School of Medicine,Baltimore,USA) discussed Celastrus as an example of Chinese herbs,which have been used in traditional Chinese medicine for centuries for the treatment of infammatory and other diseases,that can control autoimmune arthritis by altering proinfammatory cytokines and T helper 17(Th17;pathogenic cells)/T regulatory(Treg;protective cells)balance.

The afternoon session on the frst day was devoted to one plenary lecture and three oral presentations.In a plenary lecture, Dr.Mohammed A Ramadan(Cairo University,Egypt)presented the results of his frst report on antimycobacterial activity of the EgyptianEuphorbia paraliasplant and explained its importance as a promising source for antimycobacterial drugs. Dr.Hanan Alashaal(Pharmaceutical and Drug Industries Research Division,NRC)gave an oral presentation on the development of antidiabetic drugs from natural resources using the plant cell and tissue culture biotechnology.This application was based on her results on the evaluation andin vitroproduction of oral hypoglycemic agents synthesized from Solanum andBalanities aegyptiacaplants.Also,Dr.Ahmed M Alzohairy gave an oral presentation on the comparative assessments of the genotype,chemical composition and biological activities of three different Moringa species in Egypt.Finally,Dr.Hisham El-Shoky(Agriculture Research Center,Egypt)concluded in his presentation that thein vitroconfocal microscopy of SeNPs and PEGlated SeNPs confrmed the intracellular delivery of nanoparticles by endocytosis.In his experimental system,PEGSeNPs were uptaken and diffused into the Caco-2 cells within 3 hours.Also,PEG-SeNPs exhibited dose-dependent growth inhibition.

By the dawn of the second day,the whole BioNat-IV group traveled to a lovely resort along the bay of Sharm El-Sheikh. The agenda of the conference was rich and informative.The attendees participated in nine different scientifc sessions that focused on various themes in anticancer drug discovery,antiinfectives,cardiovascular drug discovery,CNS drug discovery, diabetes and obesity drug discovery,drug delivery,target identifcation and validation,chemistry of natural products and computational approaches and bioinformatics.Every session was introduced by a chairperson presenting an overview of the topic,opportunities to intervene,and challenges confronted. The frst session in Sharm El-Sheikh was introduced by Dr. Kamal Moudgil(University of Maryland School of Medicine, USA),and many important topics were discussed by several speakers in that session.

Dr.Larysa M Skivka(Taras Shevchenko Kyiv National University,Ukraine)focused on circadian control of metabolic polarization and drug sensitivity of circulating granulocytes in healthy men.While Dr.Irina Camilia CHIS(University of Medicine and Pharmacy“Iuliu Hat?ieganu,”Romania)reported that oral supplementation of Quercetin to trained diabetic rats restored endothelial function and NO bioavailability and signifcantly restored lipid peroxidation and protein carbonylation markers to near normal in the thoracic aorta. Based on these fndings,she suggested that Quercetin treatment in association with chronic moderate exercise reverses vascular endothelial dysfunction in diabetic rats.

On the third day,the morning session was chaired by Dr. HishamAl-Askary(Faculty of Pharmacy,Cairo University,Egypt). The keynote presentation for the session was by Dr.Mohamed Hassanein(Biochemistry Department,Zagazig University,Egypt). His research and presentation was focused on bioactive lipids from unconventional sources.He spotlighted the effects of fatty acids and bioactive lipids on physiological functions of the human body,and the role of oilseeds and phenolipids as a new generation of natural antioxidants with improved bioavailability.

Additional major presentations in this session from Drs. Sadish Kumar(Paramedical College(Pharmacy),Ghaziabad, India)and Salwa Mohamed Khogali(Pharmacology Central of Veterinary Research,Sudan)centered on the path that may lead to the discovery of many drugs from algae and fruits of the plants.These scientists concurred that natural products could act as potential drugs to target infammation and cancer.

The fnal session on the last day was devoted to a story of success presented by Dr Kamal D Moudgil.He spoke about his research interests which focused on two areas:frst,the induction and regulation of autoimmunity;and second,antigenprocessing and presentation.His studies are based on the rat adjuvant arthritis(AA)model of human rheumatoid arthritis (RA).He also shared a lot of his scientifc experience with the conference participants on how to navigate their professional career during and after graduate studies leading to their frst job as a scientist in academia or industry.He offered anecdotes from his own experience and that of others he was aware of in overcoming any problems that they faced as they worked to achieve their goals.

The poster sessions were chaired by Dr Mona M Marzouk (NRC,Egypt)and Dr.Mona Kassem(NRC,Egypt),with more than 60 posters competing in a fair contest and cozy atmosphere. Dr.Alaadin E.El-Haddad(Department of Pharmacognosy,Faculty of Pharmacy,University of 6th October,Egypt)presented a poster on antihyperglycemic activity and nitrile glycosides ofMoringa peregrina(Forssk.)seeds.Dr.Walaa H Salama(Department of Molecular Biology,NRC,Egypt)presented a poster on methods of purifcation and biochemical characterization of thermoactive L-amino acid oxidase isozymes from Egyptian horned viper venom.Dr Ashraf A Khalil presented a poster on enhancementofmechanicalproperties,microstructureand antimicrobial activities of zein flms cross-linked using succinic anhydride,eugenol,and citric acid[4,5].Dr.Maha M Salama (Department of Pharmacognosy,Faculty of Pharmacy,Cairo University,Egypt)presented a poster on antiprotozoal activity of the major constituents from the bioactive fraction ofVerbesina encelioides.Amira A Abdellatef(Institute of Genetic Engineering and Biotechnology,City of Scientifc Research,Borg Elarab, Alexandria,Egypt)presented a poster on lactic acid bacteria as antimycotic and antimycotoxin agents against toxigenic Fusarium species associated with maize grains stored/sold in Egyptian markets[6,7].Mariia P.Rudyk(Department of Microbiology and General Immunology,Educational and Scientifc Centre,Institute of Biology,Taras Shevchenko National University of Kyiv,Ukraine)presented interesting work on circadian control of metabolic polarization and drug sensitivity of circulating granulocytes in healthy men.

After the fnal evaluation of all presented posters,the poster presented by Dr.Shahira M Ezzat(Faculty of Pharmacy,Cairo University,Egypt)won the Award for the Best Poster.Her work was on hepatoprotective activity and UPLC-qTOF-PDA-MS profle of the anthocyanins ofHibiscus sabdariffaL.epicalyses.A couple of Complimentary Best Poster Awards were granted to Dr Mai M.Raslan(Faculty of Post Graduate Studies for Advanced Sciences,Beni-Suef University,Egypt)and Dr.Maha M Salama (Faculty of Pharmacy,Cairo University,Egypt).

Close to 25 presentations were concentrated on drug discovery and therapeutics,including natural products.The conference provided opportunities for young scientists and local scientists from Egypt to present their work to an international audience and discuss research work of mutual interest. Similarly,more than 60 students,fellows,and other trainees participated in two poster sessions that were attended by all participants.Please visit the website[8]to review previous meetings and to obtain updates and additional information for future BioNat conferences.

With the continuing success of these meetings,the ffth Euro-Mediterranean Conference of Natural Products and Drug Discovery(BioNat-V)is slated for February 2017.Please contact us if you are interested in participating,presenting,or supporting the next conference.

Acknowledgments

We sincerely acknowledge and appreciate the funding provided by The Science and Technological Development Foundation(STDF),Egypt,and The Euro Mediterranean Association of Life Sciences(EMALS)(grant number:1),which allowed us to convene this conference.We apologize to those speakers whose work could not be discussed here owing to space limitations.

R E F E R E N C E S

[1]Guidance for Industry.Botanical drug products,U.S. Department of Health and Human Services.2004.Available from:http://www.fda.gov/cder/guidance/index.htm.

[2]Dietary Supplements.U.S.Department of Health and Human Services.2015.Available from:http://www.fda.gov/Food/ DietarySupplements/default.htm.

[3]Lawson K.Botanical and Plant-derived Drugs:Global Markets. Wellesley:BCC Research;2013.

[4]Khalil AA,Deraz SF,Elrahman SA,et al.Enhancement of mechanical properties,microstructure and anti microbial activities of zein flms cross-linked using succinic anhydride, eugenol,and citric acid.Prep Biochem and Biotechnol 2015;45:551–567.

[5]Soliman EA,Khalil AA,Deraz SF,et al.Synthesis, characterization and antibacterial activity of biodegradable flms prepared from Schiff bases of zein.J Food Sci Technol 2014;51:2425–2434.

[6]Khalil AA,Abou Gabal A,Abdellatif AA,et al.Protective role of probiotic lactic acid bacteria against dietary fumonisin B1-induced toxicity and DNA-fragmentation in Sprague-Dawley rats.Prep Biochem Biotechnol 2015;45:530–550.

[7]Khalil AA,Abou Gabal A,Khaled A,et al.Lactic acid bacteria as antimycotic and antimycotoxins agents against toxigenic Fusarium species associated to maize grains stored in Egyptian markets.J Pure Appl Microbiol 2013;7(Spl.Edn.):93–105.

[8]Khalil AA.Euro-Mediterranean Conference of Natural Products and Drug Discovery.2011.Available from: www.bionats.org.

*< class="emphasis_italic">Corresponding author.

.Department of ProteinTechnology,City of Scientifc Research andTechnologicalApplications,Borg Elarab,Alexandria, Egypt.Tel.:+203–4599384;fax:+203–4599384.

E-mail address:ashraf_khalil@msn.com(A.A.Khalil).

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2016.02.002

1818-0876/?2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).