Synthesis and in vitro urease inhibitory activity of N,N'-disubstituted thioureas.
Thiourea derivatives (1-38) were synthesized and evaluated for their urease inhibition potential. The synthetic compounds showed a varying degree of in vitro urease inhibition with IC50 values 5.53 ± 0.02-91.50 ± 0.08 μM, most of which are superior to the standard thiourea (IC₅₀ = 21.00 ± 0.11 μM). In order to ensure the mode of inhibition of these compounds, the kinetic study of the most active compounds has been carried out. Most of these inhibitors were found to be mixed-type of inhibitors, except compounds 13 and 30 which were competitive, while compound 19 was identified as non-competitive inhibitor with Ki values between 8.6 and 19.29 μM.
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University Karachi, Karachi 75270, Pakistan. Electronic address: hassaan2@super.net.pk.
Khalid Mohammed
KM
Khan
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University Karachi, Karachi 75270, Pakistan.
Farzana
F
Naz
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.
Muhammad
M
Taha
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University Karachi, Karachi 75270, Pakistan.
Ajmal
A
Khan
PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
Shahnaz
S
Perveen
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University Karachi, Karachi 75270, Pakistan.
M I
MI
Choudhary
Interfakultäres Institut für Biochemie der Universität Tübingen, Hoppe-Seyler Straße 4, D-72076 Tübingen, Germany.
Wolfgang
W
Voelter
D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D013890:Thiourea / Q000493:pharmacokinetics / Q000494:pharmacology*; D014510:Urease / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D014510:Urease; D013890:Thiourea
In vitro urease inhibition activity; Kinetic study; Synthesis; Thiourea derivatives