Urease inhibition and anti-leishmanial properties of Zn(II) complexes of thiophenyl and furyl-derived C₂-symmetric ligands

Abstract

A series of Zn(II) complexes (1-4) supported by thiophenyl- and furyl-derived N,N-diamines ligands, L¹-L⁴, where L¹ = 2,2-dimethyl-N¹,N³-bis(thiophen-2-ylmethyl)propane-1,3-diamine, L² = N¹,N³-bis(thiophen-2-ylmethyl)propane-1,3-diamine, L³ = N¹,N³-bis(furan-2-ylmethyl)-2,2-dimethylpropane-1,3-diamine, and L⁴ = N¹,N³-bis(furan-2-ylmethyl)propane-1,3-diamine, were synthesized and characterized. Structural studies of 2 and 4 revealed a distorted tetrahedral geometry around the Zn(II) center. The synthesized ligands and their corresponding Zn(II) complexes were tested in vitro for urease inhibitory potential against Jack bean urease (JB urease) and Bacillus pasteurii urease (BP urease). Complex 2, possessing a thiophenyl pendant moiety, exhibited considerable inhibitory potential against JB urease (IC₅₀ = 5.5 ± 0.15 μM) and BP urease (IC50 = 6.0 ± 0.12 μM) relative to the standard thiourea (IC₅₀ = 10 ± 0.52 and 8.20 ± 0.90 μM, respectively). Additionally, molecular docking confirmed the probable binding modes of the active complexes in the crystal structure of the JB urease. The synthesized ligands and complexes were also screened for anti-leishmanial activity and were proven to be effective against the Leishmania parasite.

Graphical Abstract

Keywords:

• Zn(II) complexes
• tetrahedral geometry
• urease inhibition
• anti-leishmanial properties
• molecular docking

Authors’ contributions

Saira Nayab contributed to conceptualization; supervision-lead; writing an original draft, formal analysis; Momin Khan contributed to biological studies; Yerim Cho contributed to supporting; Hyosun Lee contributed to review-editing, validation-supporting.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by the Higher Education Commission (HEC), Islamabad, Islamic Republic of Pakistan, under the National Research Program for Universities (NRPU) [Grant No. 6840-KP]. X-ray crystallography with PLS-II 2D-SMC beamline was supported by MSIP and POSTECH, Republic of Korea. Molecular docking studies were performed in the Department of Biochemistry (AWKUM), Khyber Pakhtunkhwa, Islamic Republic of Pakistan by Dr. Farman A. Khan.