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Design and synthesis of guanylthiourea derivatives as potential inhibitors of Plasmodium falciparum dihydrofolate reductase enzyme
Affiliation:1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali 160062, Punjab, India;2. Department of Biochemistry, Mahidol University, Bangkok 10400, Thailand;1. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar 160 062, Punjab, India;2. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar 160 062, Punjab, India;1. Department of Chemistry, Tripura University (A Central University), Suryamaninagar, Tripura 799 022, India;2. Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, Howrah 711 103, India;3. Department of Physics, M.B.B. College, Agartala, Tripura 799 004, India;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar 160 062, Punjab, India;2. Department of Pharmacy, Birla Institute of Technology & Science – Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India;1. MLS Professor׳s Unit, Indian Association for the Cultivation of Science, 2A & 2B Raja S.C. Mullick Road, Kolkata 700032, India;2. School of Materials Science and Engineering, Kensington, University of New South Wales, Sydney 2052, Australia;3. Department of Physics, Rammohan College, 102/1 Raja Rammohan Roy Sarani, Kolkata 700009, India;4. Department of Physics, Gurudas College, Kolkata 700054, India;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, Punjab 160 062, India;2. Department of Pharmacy, Birla Institute of Technology & Science—Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India;1. Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433, PR China;2. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
Abstract:A new class of compounds based on S-benzylated guanylthiourea has been designed as potential PfDHFR inhibitors using computer aided methods (molecular electrostatic potential, molecular docking). Several compounds in this class have been synthesized starting from guanylthiourea and alkyl bromides. In vitro studies showed that two compounds from this class are active with the IC50 value of 100 μM and 400 nM.
Keywords:Antimalaria  Guanylthiourea  MESP  Molecular docking
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