Novel nano-sized metal complexes based on aceclofenac and glycine ligands: Synthesis, Characterization, molecular docking studies and their enhanced efficacy in ameliorating testicular and spermatological oxidative damages in male rats.

Rats-treated with Acecl showed marked-atrophy of seminiferous-tubules, arrested-spermatogenesis and sperm-deformation, while animals-treated with Zr(IV)-complex showed testicular-histo-architecture improvement back towards healthy-tissues. Regarding molecular-docking, binding affinities of Zr(IV)-complex to anti-oxidative-enzymes; SOD, CAT and pro-apoptotic; P53 higher than corresponding parent-ligand Acecl , giving the opportunity to Zr(IV)-complex to attenuating oxidative-damages (testicular-tissue-atrophy) caused by Acecl. [Display omitted] • Synthesis of new mixed complexes of Cu(II), Zr(IV), La(III), Th(IV) and U(VI) with Acecl in presence of Gly. • Characterization for Acecl , Gly and their metal-complexes with different techniques. • Acecl -treated rats showed higher levels of oxidants with inhibition of anti-oxidants activities. • Acecl -treatment triggered testicular cell apoptosis by rising P53 and lowering BCL2 proteins. • Acecl-metal complexes ameliorate testicular oxidative toxicity back towards healthy rats. New nano metal complexes of Cu(II), Zr(IV), La(III), Th(IV) and U(VI) ions using Acecl as primary ligand and glycine (Gly) as secondary ligand were synthesized and characterized. Physico-chemical and spectroscopic techniques namely, elemental (CHN), molar-conductance (Λ), magnetic susceptibility (µeff), ultraviolet–visible (UV–Vis.), Fourier-transform-infrared (FT-IR), proton-nuclear-magnetic-resonance (1H NMR), x-ray-diffraction (XRD), mass-spectrometry (m/z), and thermal-analyses (TG-DTG/DTA), were utilized to determine the binding mode and composition of the complexes. FT-IR spectra revealed that Acecl chelated as negative bidentate mode to the metal ions via oxygen of carboxylic and keto groups while, Gly chelated as negative bidentate via nitrogen of amino group and deprotonated carboxylic oxygen. Λ values revealed that La(III) and Th(IV) complexes were 1:1 and 1:2 electrolytes. XRD designated the formation of metal complexes, in which their structures changed from ligands due to presence of metal ions and all complexes found as crystalline in phase. Forty-two male-albino-rats categorized into seven groups, comprising healthy, Acecl treated and its metal complexes groups were examined. Treatment with Acecl showed severe testicular-toxicity, manifested by severe atrophy in seminiferous tubules, arrested spermatogenesis and negatively-altered semen parameters. Such oxidative-damages recognized by elevated oxidants levels, reduced anti-oxidant activities and up-regulated testicular cell pro-apoptotic-P53. Contrarily, metals complexation, particularly Zr(IV) complex, protected testes from Acecl -induced testicular-apoptosis through increasing pro-survival-BCL2, lowering pro-apoptotic-P53, reducing oxidant levels and stimulating anti-oxidants activities. Consequently, marked improvements in testicular histo-architecture, spermatognial maturation and sperm characteristics towards the healthy were noticed. Regarding molecular docking, Zr(IV)-complex experienced the best binding affinities with superoxide-dismutase, catalase and P-53 targets. ADME-Tox prediction of novel metal complexes revealed their acceptable drug-likeness properties. [ABSTRACT FROM AUTHOR]