Abstract: This lecture will be focused on two parts. In the first part, we will present diarylphosphonate inhibitors for urokinase-type plasminogen activator (uPA) with anticancer activity. Urokinase-type plasminogen activator (uPA) is a serine protease which is situated on the cell surface and can be bound to its receptor (uPAR). The role of uPA/uPARsystem in human cancer was demonstrated (Thromb. Haemostasis 2005, 93, 641).We have designed and developed peptidicdiphenylphosphonate inhibitors of uPA^.. A first potent and selective lead compounds were identified and a lead optimization program was started to modify the compounds to a small non-peptidicdiarylphosphonate irreversible inhibitor of uPA (J. Med. Chem. 2006, 49, 5785, ibid,J. Med. Chem. 2007, 50, 6638, J. Iran. Chem. Soc. 17, 1211 (2020). Biomedicines 9, 1767, 2021). Potent and selective uPA inhibition was obtained (IC₅₀< 10 nM; selectivity toward a set of other trypsine like serine proteases more than 1000 fold). The synthetic approach, structure activity relationship (SAR) and in vivo animal studies of these selective inhibitors will be presented.  While the Part II of my lecture will deal with the development of neocryptolepine scaffolds as a novel antimalarial active agents.As part of a larger project for developing more potent and safer antimalarial lead compounds based on natural product,  we have developed robust and efficient synthetic method for the natural product alkaloid, neocryptolepine (J. Med. Chem. 52, 2979, 2009), ibid, 56, 1431, 2013) isolated from the shrub Cryptolepissanguinolenta used in Central and West Africa in traditional medicine for the treatment of malaria.  A lead optimization program was started to modify the compound and a wide range of neocryptolepine analogues with diversified frameworks and drug-like properties were synthesized. Potent and selective analogues against malaria as well as cancer with IC₅₀ in the low nanomolar range were obtained (Med. Chem. Commun.5, 927, 2014), European Journal of Medicinal Chemistry 64, 498, 2013, Medicinal  Chemistry  Research  25, 879 (2016), Molecules 22, 1954 (2017), ibid, 24, 2121(2019), ibid, 26, 754, (2021). The synthetic routes of these molecules, their anticancer and antimalarial activities as well as the proposed mechanism of action will be illustrated from both our own research and literature.

Dr. Ibrahim Tantawy is a Professor of Medicinal Chemistry, Faculty of Science, Menoufia University, Egypt. His main research theme focused on drug discovery and development, through chemical synthesis, of new candidate drug for treatment of the world’s deadliest diseases such as cancer & Malaria. He received his PhD (1994) from MU and Aarhus University, Denmark. After PhD he spent many years of postdoctoral positions & as a visiting Professor at Vienna Univ. (Austria), Univ. of Tokyo (Japan), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan),  Uppsala Univ. (Sweden), Univ. of Antwerp (Belgium),. Okayama Univ. (Japan), Nagoya Univ. (Japan), Chinese Academy of Science (CAS) -Visiting Professor, Institute of Process Engineering, Beijing, China.  Currently he is the President of Japan Society for The Promotion of Science Alumni Association in Egypt (JSPSAAE) since 2012 and Head of Chemistry Department, Menoufia University.  He received many international awards including WHO Innovation Award and Japan’s Foreign Minister’s Commendation Award for 2021 He has published  over 100 papers, patents & book chapters  in  peer reviewed international  journals. Currently he acts as a editorial board member and reviewer for many international journals. Reviewer of the Promotion Committees of the Supreme Council of Egyptian Universities and Research Institutions. Board Member of  International Green Technology Association (IGTA), Chinese Academy of Sciences (CAS).

Currently he is PI of two  international funded projects: 1. Applications of Ecofriendly Ionic Liquids for Smart and Green valorization of Waste Biomass into Liquid Fuels. Joint funded through Egyptian-Chinese-Research Fund from STDF-MOST. 2. Design and Synthesis of Novel Alkaloids with Natural Origin as Anticancer Agent”. Joint funded through Egyptian and Japanese Scientific Cooperation (JEJSC) between STDF & JSPS). https://www.scopus.com/authid/detail.uri?authorId=7004479185