DOI: 10.6084/m9.figshare.27060503.v1
title: Exploration of newly synthesized transition metal(II) complexes for infectious diseases

description: <b>Aim:</b> In the annals of human history, infectious diseases significantly influencing the collective well-being of people worldwide. Consequently, to identify effective agents for infectious ailments, the octahedral Co(II), Ni(II), Cu(II), Zn(II) complexes of 4-(3-methoxyphenyl)pyrimidin-2-amine and 2-methoxy-1-napthaldehyde based ligand were synthesized and well characterized in the current investigation. <b>Results & methodology:</b> The synthesized compounds were evaluated for anti-TB, anti-inflammatory, antibacterial, antifungal activities by microplate Alamar blue, bovine serum albumin, serial dilution assays. The [Zn(L<sup>1</sup>)<sub>2</sub>(H<sub>2</sub>O)<sub>2</sub>] complex <b>(5)</b> demonstrates robust potency with 0.0040 ± 0.0007 and 0.0038 μmol/ml MIC value in anti-tuberculosis and antimicrobial activities, correspondingly while 06.57 ± 0.03 μM IC<sub>50</sub> value in anti-inflammatory investigation. <b>Conclusion:</b> Complex (5) show promising potential as targets for pathogen deformities, supported by rigorous biological and computational investigations including pharmacophore modelling, molecular docking (binding score -121.018 and -59.8662 kcal/mol for 6H53 and 1CX2 proteins, respectively), DFT (Density functional theory), MESP (Molecular Electrostatic Potential) and ADMET (absorption, distribution, metabolism, excretion and toxicity). Antituberculosis, anti-inflammation, antibacterial, antifungal activities of newly synthesized and well characterized transition metal complexes of heterocyclic Schiff base ligand. Further, molecular docking, pharmacophore modeling, DFT, MESP and AMDET computational studies were performed to validate the <i>in vitro</i> results which gives a new insight in the research. The proliferation of pathogenic deformities remains a primary contributor to mortality rates, underscoring the urgent need to identify selective agents capable of targeting pathogens causing ailments. This research represents the synthesis of Co(II), Ni(II), Cu(II), Zn(II) complexes of heterocyclic Schiff base ligand which are based on 4-(3-methoxyphenyl)pyrimidin-2-amine and 2-methoxy-1-napthaldehyde. The purity and structure elucidation of the compounds were demonstrated by mass spectrometry, UV-Vis, NMR, FTIR, powder XRD, TGA, SEM, molar conductance, elemental analysis and magnetic susceptibility. The instrumental analysis confirmed the octahedral environment around central metal atom which bonded <i>via</i> nitrogen, oxygen atoms of the bidentate ligand and oxygen atoms of two water molecules. The synthesized compounds were evaluated for <i>in vitro</i> anti-TB, anti-inflammatory, antibacterial, antifungal activities by microplate Alamar blue, bovine serum albumin, serial dilution assays. <i>In vitro</i> anti-TB activity of the compounds (1–10) was assessed by <i>against M. tuberculosis</i> H<sub>37</sub>R<sub>v</sub> strain which revealed that the [Zn(L<sup>1</sup>)<sub>2</sub>(H<sub>2</sub>O)<sub>2</sub>] <b>(5)</b> was reported as three-times more effective compared with streptomycin with MIC value of 0.0040 ± 0.0007 μmol/ml against TB dysfunction. Anti-inflammatory investigation revealed that <b>(5)</b> has significant efficacy against inflammation as indicated by comparable IC<sub>50</sub> value (06.57 ± 0.03 μM) to standard drug whereas <b>(5)</b> (0.0038 μmol/ml MIC value) was also reported as highly potent for tested microbial strains than standard drugs. Further, the compounds (1–5) were scrutinized by using various computational studies such as molecular docking, pharmacophore modelling, DFT, MESP and ADMET. Computational studies have substantiated the bioactivity of complex (5), indicating its potential application as a biological agent in health cares for TB, inflammation and as antioxidant. Thus, biological and computational investigations provide compelling evidence supporting the more potency of the Zn(II) complex (5).