Synthesis, Characterization And Biological Studies Of Cr(Iii), Cu(Ii) And Zn(Ii) Complexes Of Metformin And Novel Oxo Ligands: A Combined Experimental And Computational Study

Abstract

The Synthesis And Use Of Transition Metal Complexes For Medical And Health Related Applications Has Gained Momentum In Recent Years. Transition Metal Complexes Offer A Rich Platform For Useas Therapeutic Agents Ranging From Antimicrobial And Anti-Inflammatory To Anti-Proliferative And Enzyme Inhibitory Activities. Their Unique Electronic And Stereochemical Properties: Molecular Geometries, Ligand Exchange, Redox, Catalytic, And Photophysical Reactions Are Among The Major Reasons For The Convergence Of Attention Towards The Compounds?�? Both Therapeutic And Diagnostic Roles. Even Though Promising Results Are Reported And Different Metal Complexes Are Under Clinical Trial, The Incidence And Death Associated To Oxidative Stress, Microbial Infection, Antimicrobial Resistance And Cancer Are Rapidly Increasing. These Urged Us To Synthesize Metal Complexes Using Novel Ligand Screening Tools And Drug Repositioning Strategies. In This Work, Cr(Iii), Cu(Ii) And Zn(Ii) Heteroleptic Complexes Of Metformin And Oxo-Ligands Were Synthesized And Subjected To Cytotoxicity, Antibacterial And Antioxidant Activity Evaluations. A Naturally Available Ligand Chrysin Was Employed After A Series Of In-Silico Aided Screening Protocols Which Showed Its Drug Like Molecular Nature And Potential For Complexation With Metals. Metformin And Ciprofloxacin Drugs As Well As 1,10-Phenathroline Were Also Used As Ligands For The Synthesis Of The Metal Complexes. The Synthesized Metal Complexes Were Characterized Using Uv-Vis, Ftir, Ms, Sem-Edx, Tga/Dta, Xrd And Molar Conductance Measurements. In Order To Support And Well Describe The Experimental Results Dft, Td-Dft, In-Silico Admet And Molecular Docking Computational Tools Were Employed. All The Synthesized Complexes Were Confirmed To Possess Polycrystalline Natures With Average Crystallite Sizes Ranging From 18 ?�? 36 Nm. Furthermore, Mixed Ligand Complexes Of Wide Range Crystalline Materials With Percent Crystalline Index Ranging From 22 ?�? 94% Were Synthesized. Biologically, In-Vitro Cytotoxic Activity Against Human Breast Adenocarcinoma Cancer Cell Line (Mcf-7), Antibacterial Activity Against Two Gram-Negative (E.Coli And P. Aeruginosa) And Two Gram-Positive (S. Aureus And S. Pyogenes) Bacterial Strains, And Antioxidant Activity Against Dpph Radical Were Evaluated. The Statistical Analysis (Anova) For Significance Difference (P < 0.05) Showed That Variations In Metal Center And Concentration Have Significance Effect On The Bacterial Activity Of The Metal Complexes. Promising Results From The In Vitro Cytotoxic Activity With Ic50 Value Ranging 3.72 ?�? 44.88 ??M Compared To The Positive Control Cisplatin (18.62 ??M) Were Found. Among The Synthesized Complexes Three Cu(Ii) Complexes That Consists Of 1,10-Phenathroline And Chrysin (55), 1,10-Phenathroline And Metformin (60) And,Xx1,10-Phenathroline And Ciprofloxacin (61) Were Found To Show Unique Cytotoxicity Profile With Ic50 Values Of 3.72,4.29 And 7.58 ??M, Respectively. A Cr(Iii) Complex (54) Of 1,10-Phenathroline And Chrysin Was Found To Be The Fourth Cytotoxic Complex Against Mcf-7 Cell Lines W