title: Urease inhibition and anti-leishmanial assay of substituted benzoylguanidines and their copper(II) complexes.
abstract: A series of N,N',N''-trisubstituted guanidines (1-6) and their copper(II) complexes, [κ(2)(O,N)-C(6)H(5)CONHC(NHC(6)H(4)Cl)NR](2)Cu(ii) (R = iso-propyl (1a), n-butyl (2a), sec-butyl (3a), tert-butyl (4a), benzyl (5a), and para-tolyl (6a)) were synthesized and characterized using elemental analysis, FTIR and NMR spectroscopy. DFT studies were used to assess the location of the protons in the free ligands. However, calculations have shown that, in all cases, hydrogen bonding from either N-H group gives conformations that are very similar in energy. Single crystal XRD studies were used to characterize ligands 1 and 4 and the related complexes 1a and 4a. The structures reveal that these complexes are mononuclear in the solid state and that copper adopts a regular square planar geometry. In both metallic species, the N, N', N''-trisubstituted guanidine ligands chelate the Cu(II) atom using the oxygen and one nitrogen. The synthesized compounds were investigated for urease inhibition using thiourea as a standard drug. Most complexes exhibit a better activity than the respective guanidines and compound 1a was found to be the most active with IC(50) = 9.83 ± 0.07 μM (the IC(50) for thiourea is 21.0 ± 0.1 μM). The species were also screened for their anti-leishmanial activity. However, all of the compounds were devoid of any significant activity.
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Murtaza
authors.forename: Amin
authors.initials: A
authors.lastname: Badshah
authors.forename: Muhammad
authors.initials: M
authors.lastname: Said
authors.forename: Hizbullah
authors.initials: H
authors.lastname: Khan
authors.forename: Ajmal
authors.initials: A
authors.lastname: Khan
authors.forename: Samreen
authors.initials: S
authors.lastname: Khan
authors.forename: Sadia
authors.initials: S
authors.lastname: Siddiq
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
authors.forename: Josée
authors.initials: J
authors.lastname: Boudreau
authors.forename: Frédéric-Georges
authors.initials: FG
authors.lastname: Fontaine
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D007887:Fabaceae / Q000201:enzymology; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D006146:Guanidines; D009942:Organometallic Compounds; D003300:Copper; D014510:Urease