title: Ferrocene-based guanidine derivatives: in vitro antimicrobial, DNA binding and docking supported urease inhibition studies.
abstract: Some novel ferrocenyl guanidines 1-8 were synthesized and characterized by different spectroscopic methods, elemental analysis and single crystal X-rays diffraction techniques. The crystallographic studies revealed that the existence of the strong non-bonding interactions facilitate these molecules to interact with biological macro-molecules like DNA that described to inherit good biological activities. The DNA interaction studies carried out by cyclic voltammetry (CV) and UV-visible spectroscopy are in close agreement with the binding constants (K) (0.79-5.4) × 10(5) (CV) and (0.72-5.1) × 10(5) (UV-vis). The shift in peak potential, current and absorption maxima of the studied ferrocenyl guanidines in the presence of DNA revealed that CV coupled with UV-vis spectroscopy could provide an opportune to characterize metal-based compounds-DNA interaction mechanism, a prerequisite for the design of new anticancer agents and understanding the molecular basis of their action. The compounds 1-8 have been screened for their antibacterial, antifungal and urease inhibition potency. A concurrent in silico study has also been applied on ferrocene moiety impregnated guanidines 1-8 to identify most active compounds having for inhibiting the activity of urease (pdb id 3LA4). Most of the compounds were found as potent inhibitors of urease and the compound 1 was found to be the most active with an IC50 of 16.83 ± 0.03 μM. The docking scores are in close agreement with the in vitro obtained IC50 values of inhibitors 1-8.
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Gul
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: mkhawarrauf@yahoo.co.uk.
authors.forename: Muhammad Khawar
authors.initials: MK
authors.lastname: Rauf
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: aminbadshah@yahoo.com.
authors.forename: Amin
authors.initials: A
authors.lastname: Badshah
authors.affiliation: National Center for Bioinformatics, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Syed Sikander
authors.initials: SS
authors.lastname: Azam
authors.affiliation: Department of Physics, Sargodha University, Sargodha 40100, Pakistan.
authors.forename: Muhammad Nawaz
authors.initials: MN
authors.lastname: Tahir
authors.affiliation: Department of Chemistry, Gomal University, Dera Ismail Khan 29050, Pakistan.
authors.forename: Azim
authors.initials: A
authors.lastname: Khan
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D032449:Canavalia / Q000201:enzymology; D004247:DNA / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005296:Ferrous Compounds / Q000737:chemistry*; D005658:Fungi / Q000187:drug effects; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D000075163:Metallocenes; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D014510:Urease / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D006146:Guanidines; D000075163:Metallocenes; D004247:DNA; D014510:Urease; C004998:ferrocene
keywords: Antimicrobial; DNA interaction; Ferrocene-based guanidines; Urease docking; Urease inhibition