title: Synthesis, characterization and urease inhibition, in vitro anticancer and antileishmanial studies of Ni(II) complexes with N,N,N'-trisubstituted thioureas.
abstract: A series of N,N,N'-trisubstituted thioureas (1-12) and their Ni(II) complexes (1a-12a) were synthesized and characterized by multinuclear ((1)H and (13)C) NMR, FT-IR spectroscopy and LC-MS techniques in combination with elemental analysis. The crystal structures of both ligands and Ni(II) chelates of type Ni(L-O, S)2 were determined by single crystal X-ray diffraction analysis. All the complexes were adopted to have square planar geometry, where the N,N,N'-trisubstituted thioureas showed bidentate mode of coordination at nickel centre through oxygen and sulfur atoms. The synthesized complexes were screened for potential inhibitors of Jack bean urease. Compounds 1a and 3a were observed as most potent inhibitors of urease exhibiting IC50 values of 1.17 ± 0.12 and 1.19 ± 0.41 µM, respectively. Cytotoxicity assay on lung carcinoma (H-157) and kidney fibroblast (BHK-21) cell showed that compounds were significant anticancer agents. Additionally, the complexes were tested against Leishmania major and found to be potent antileishmanial agents.
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Muhammad Khawar
authors.initials: MK
authors.lastname: Rauf
authors.forename: Samad
authors.initials: S
authors.lastname: Yaseen
authors.forename: Amin
authors.initials: A
authors.lastname: Badshah
authors.forename: Sumera
authors.initials: S
authors.lastname: Zaib
authors.forename: Raffia
authors.initials: R
authors.lastname: Arshad
authors.lastname: Imtiaz-Ud-Din
authors.forename: Muhammad Nawaz
authors.initials: MN
authors.lastname: Tahir
authors.forename: Jamshed
authors.initials: J
authors.lastname: Iqbal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001681:Biological Assay; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D009532:Nickel / Q000737:chemistry*; D013890:Thiourea / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014510:Urease / Q000037:antagonists & inhibitors*; D014709:Vero Cells
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D014344:Trypanocidal Agents; D009532:Nickel; D014510:Urease; D013890:Thiourea