<i>In vitro</i> α-glucosidase, docking and density functional theory studies on novel azide metal complexes
Creators: name: Avcı, Davut
name: Özge, Özgen
name: Sönmez, Fatih
name: Tamer, Ömer
name: Başoğlu, Adil
name: Atalay, Yusuf
name: Kurt, Belma Zengin
Publisher: name: Taylor & Francis
Year: 2024
Subjects: Biophysics
Biochemistry
Space Science
Medicine
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified

description: <b>Aim:</b> The goal of this study is to synthesize new metal complexes containing <i>N</i>-methyl-1-(pyridin-2-yl)methanimine and azide ligands as α-glucosidase inhibitors for Type 2 diabetes. <b>Materials &amp; methods:</b> The target complexes (<b>12–16</b>) were synthesized by reacting <i>N</i>-methyl-1-(pyridin-2-yl)methanimine (L<sub>1</sub>) with sodium azide in the presence of corresponding metal salts. The investigation of target protein interactions, vibrational, electronic and nonlinear optical properties for these complexes was performed by molecular docking and density functional theory studies. <b>Results:</b> Among these complexes, complex <b>13</b> (IC<sub>50</sub> = 0.2802 ± 0.62 μM) containing Hg ion showed the highest α-glucosidase inhibitory property. On the other hand, significant results were detected for complexes containing Cu and Ag ions. <b>Conclusion:</b> Complex <b>13</b> may be an alternate anti-diabetic inhibitor according to <i>in vitro</i>/docking results. In this study, new effective α-glucosidase inhibitor series of Schiff base-azide metal complexes {[Cu<sub>2</sub>(L<sub>1</sub>)<sub>2</sub>(N<sub>3</sub>)<sub>3</sub>], (<b>12</b>), [Hg(L<sub>1</sub>)<sub>2</sub>(N<sub>3</sub>)·H<sub>2</sub>O] (<b>13</b>), [Cd(L<sub>1</sub>)<sub>2</sub>(N<sub>3</sub>)], (<b>14</b>), [Ag(L<sub>1</sub>)(N<sub>3</sub>)<sub>2</sub>·2H<sub>2</sub>O], (<b>15</b>), [Zn<sub>2</sub>(L<sub>1</sub>)<sub>2</sub>(N<sub>3</sub>)<sub>2</sub>Cl<sub>2</sub>·4H<sub>2</sub>O], (<b>16</b>); L<sub>1</sub>: <i>N</i>-methyl-1-(pyridin-2-yl)methanimine} were synthesized. The electronic spectral features for these complexes characterized by <sup>1</sup>H and <sup>13</sup>C NMR (except for complex <b>12</b> including Cu ion), mass (LC-HRMS) and FT–IR spectra were examined by UV–Vis spectra. In complexes <b>12–16</b>, being α-glucosidase inhibitory potential, the IC<sub>50</sub> values of 0.2802 ± 0.62 and 420.88 ± 1.42 μM range were obtained. Considering the CAM-B3LYP and ωB97XD/6–311+G(d,p)//LanL2DZ levels of density functional theory (DFT), the optimal ground state geometries and vibrational wavenumbers of the complexes <b>12–16</b> were computed, and the obtained results were compared with the corresponding experimental wavenumbers. The corresponding theoretical wavelengths, oscillator strengths as well as major contributions to the electronic transitions were calculated at TD-DFT/ωB97XD and TD-DFT/CAM-B3LYP levels. Additionally, the molecular orbitals and atoms/functional groups that make important contributions to electronic transitions were determined with the SWizard and Chemissian programs. Moreover, to survey nonlinear optical parameters of the complexes <b>12–16</b>, the CAM-B3LYP and ωB97XD/6–311+G(d,p)//LanL2DZ levels of density functional theory were used. Demonstration of target protein interactions with complexes <b>12–16</b> has been fulfilled by molecular docking studies. It is deduced that while IC<sub>50</sub> results of the <b>15</b> and <b>12</b> against α-glucosidase are obtained remarkably, the β and γ results that complexes <b>15</b> and <b>12</b> are highly efficient in terms of microscopic second- and third-nonlinear optics properties, respectively. The experimental vibrational wavenumbers and absorption wavelength results were compared with corresponding theoretical ones, it was observed that the results were quite compatible.