TY - JOUR
T1 - Novel Ag(I) and Zn(II) complexes based on benzenesulfonamide ligand
T2 - synthesis, characterization, and biological evaluation as multitarget antidiabetic agents
AU - Ayoup, Mohammed Salah
AU - Yasser, Mennatallah
AU - Soliman, Saied M.
AU - Abdel-Hamid, Hamida
AU - Cordes, David Bradford
AU - McKay, Aidan
AU - Ghareeb, Doaa A.
AU - Elghamry, Ibrahim
AU - Ashraf, Samah
AU - Sonousi, Amr
AU - Kassab, Asmaa E.
AU - Yousri, Amal
N1 - Funding: This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia (Project No. KFU250713).
PY - 2025/3/7
Y1 - 2025/3/7
N2 - Three novel d10-metal complexes of the antidiabetic sulfonamide ligand (HPPS) were synthesized and characterized using elemental analysis, FTIR, NMR spectra, and single-crystal X-ray structure. The two Ag(I) complexes share the common cationic formula [Ag(HPPS)2]+, abbreviated as [1]. The structure of the /studied Ag(I) complexes could be represented by the formula [1]ClO4·2H2O and [1]NO3·CH3CN. Both complexes are mononuclear, where Ag(I) is tetra-coordinated with two neutral HPPS units as bidentate ligands via the pyrazole and pyridine N-atoms. In both cases, the coordination geometry around Ag(I) is a twisted form that is intermediate between tetrahedral and square planar geometry. The Zn(II) complex [Zn4(PPS)2Cl6(H2O)2]·2EtOH, 2, is tetra-nuclear in which the Zn(II) ions are tetra- and penta-coordinated. The anionic PPS- ligand acts as a bis-bidentate ligand, bridging both independent Zn(II) sites, which are then further bridged by chloride ions to adjacent zincs. The synthesized complexes were evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities and glucose uptake. The results revealed that the synthesized Ag(I) and Zn(II) complexes showed remarkably excellent antidiabetic potential. Interestingly, α-glucosidase and α-amylase inhibitory activities and glucose uptake efficacy of Ag(I) and Zn(II) complexes highly surpassed their free ligand HPPS. Ag(I) complexes )[1]ClO4·2H2O and [1]NO3·CH3CN ( and Zn(II) complex )2( showed excellent inhibitory potential against α-glucosidase with IC50 values of 3.68, 5.22, and 3.93 µM, respectively (2.13, 1.5, and 2 times more potent than acarbose). Ag(I) complex, [1]ClO4·2H2O and Zn(II) complex, 2 (IC50 values of 2.78 and 4.93 µM) exhibited significant α-amylase inhibitory potential, 4.8- and 2.7- fold more potent than acarbose. Ag(I) and Zn(II) complexes showed 3.38- to 3.89-fold more glucose uptake efficacy than berberine with EC50 values of 12.01, 11.15, and 10.45 µM, for [1]ClO4·2H2O, [1]NO3·CH3CN and 2, respectively. Docking studies were conducted for the synthesized silver and zinc complexes using α-glucosidase protein (PDB:2QMJ) and α-amylase (PDB:1XCW) complexed with acarbose. Keywords: Ag(I) and Zn(II) complexes; Sulfonamide; α-Glucosidase; α-Amylase; Glucose uptake; Antidiabetic.
AB - Three novel d10-metal complexes of the antidiabetic sulfonamide ligand (HPPS) were synthesized and characterized using elemental analysis, FTIR, NMR spectra, and single-crystal X-ray structure. The two Ag(I) complexes share the common cationic formula [Ag(HPPS)2]+, abbreviated as [1]. The structure of the /studied Ag(I) complexes could be represented by the formula [1]ClO4·2H2O and [1]NO3·CH3CN. Both complexes are mononuclear, where Ag(I) is tetra-coordinated with two neutral HPPS units as bidentate ligands via the pyrazole and pyridine N-atoms. In both cases, the coordination geometry around Ag(I) is a twisted form that is intermediate between tetrahedral and square planar geometry. The Zn(II) complex [Zn4(PPS)2Cl6(H2O)2]·2EtOH, 2, is tetra-nuclear in which the Zn(II) ions are tetra- and penta-coordinated. The anionic PPS- ligand acts as a bis-bidentate ligand, bridging both independent Zn(II) sites, which are then further bridged by chloride ions to adjacent zincs. The synthesized complexes were evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities and glucose uptake. The results revealed that the synthesized Ag(I) and Zn(II) complexes showed remarkably excellent antidiabetic potential. Interestingly, α-glucosidase and α-amylase inhibitory activities and glucose uptake efficacy of Ag(I) and Zn(II) complexes highly surpassed their free ligand HPPS. Ag(I) complexes )[1]ClO4·2H2O and [1]NO3·CH3CN ( and Zn(II) complex )2( showed excellent inhibitory potential against α-glucosidase with IC50 values of 3.68, 5.22, and 3.93 µM, respectively (2.13, 1.5, and 2 times more potent than acarbose). Ag(I) complex, [1]ClO4·2H2O and Zn(II) complex, 2 (IC50 values of 2.78 and 4.93 µM) exhibited significant α-amylase inhibitory potential, 4.8- and 2.7- fold more potent than acarbose. Ag(I) and Zn(II) complexes showed 3.38- to 3.89-fold more glucose uptake efficacy than berberine with EC50 values of 12.01, 11.15, and 10.45 µM, for [1]ClO4·2H2O, [1]NO3·CH3CN and 2, respectively. Docking studies were conducted for the synthesized silver and zinc complexes using α-glucosidase protein (PDB:2QMJ) and α-amylase (PDB:1XCW) complexed with acarbose. Keywords: Ag(I) and Zn(II) complexes; Sulfonamide; α-Glucosidase; α-Amylase; Glucose uptake; Antidiabetic.
KW - Ag(I) and Zn(II) complexes
KW - Sulfonamide
KW - α-Glucosidase
KW - α-Amylase
KW - Glucose uptake
KW - Antidiabetic
U2 - 10.1016/j.ica.2025.122639
DO - 10.1016/j.ica.2025.122639
M3 - Article
SN - 0020-1693
VL - 582
JO - Inorganica Chimica Acta
JF - Inorganica Chimica Acta
M1 - 122639
ER -