title: Design and synthesis of guanylthiourea derivatives as potential inhibitors of Plasmodium falciparum dihydrofolate reductase enzyme.
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.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali 160062, Punjab, India.
authors.forename: Legesse
authors.initials: L
authors.lastname: Adane
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali 160062, Punjab, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Bhagat
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali 160062, Punjab, India.
authors.forename: Minhajul
authors.initials: M
authors.lastname: Arfeen
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali 160062, Punjab, India.
authors.forename: Sonam
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Department of Biochemistry, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Rachada
authors.initials: R
authors.lastname: Sirawaraporn
authors.affiliation: Department of Biochemistry, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Worachart
authors.initials: W
authors.lastname: Sirawaraporn
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali 160062, Punjab, India.
authors.forename: Asit K
authors.initials: AK
authors.lastname: Chakraborti
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali 160062, Punjab, India. Electronic address: pvbharatam@niper.ac.in.
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Bharatam
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006164:Guanylthiourea / Q000138:chemical synthesis* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase; D006164:Guanylthiourea
keywords: Antimalaria; Guanylthiourea; MESP; Molecular docking; PfDHFR