Insights into Structure and Biological Activity of Copper(II) and Zinc(II) Complexes with Triazolopyrimidine Ligands

In an attempt to increase the biological activity of the 1,2,4-triazolo[1,5-a]pyrimidine scaffold through complexation with essential metal ions, the complexes trans-[Cu(mptp)₂Cl₂] (1), [Zn(mptp)Cl₂(DMSO)] (2) (mptp: 5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine), [Cu₂(dmtp)₄Cl₄]·2H₂O (3) and [Zn(dmtp)₂Cl₂] (4) (dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine), were synthesized and characterized as new antiproliferative and antimicrobial species. Both complexes (1) and (2) crystallize in the P2₁/n monoclinic space group, with the tetrahedral surroundings generating a square-planar stereochemistry in the Cu(II) complex and a tetrahedral stereochemistry in the Zn(II) species. The mononuclear units are interconnected in a supramolecular network through π–π interactions between the pyrimidine moiety and the phenyl ring in (1) while supramolecular chains resulting from C-H∙∙∙π interactions were observed in (2). All complexes exhibit an antiproliferative effect against B16 tumor cells and improved antibacterial and antifungal activities compared to the free ligands. Complex (3) displays the best antimicrobial activity against all four tested strains, both in the planktonic and biofilm-embedded states, which can be correlated to its stronger DNA-binding and nuclease-activity traits.     

Synthesis, spectroscopic characterization and in vitro antimicrobial activity of diorganotin(IV) dichloride adducts with [1,2,4]triazolo-[1,5-a]pyrimidine and 5,7-dimethyl-[1,2,4]triazolo-[1,5-a]pyrimidine

The heterocyclic ligands [1,2,4]triazolo-[1,5-a]pyrimidine (tp) and 5,7-dimethyl-[1,2,4]triazolo-[1,5-a]pyrimidine (dmtp), react with diorganotin dichlorides giving the addition compounds Me₂SnCl₂(tp)₂, Et₂SnCl₂(tp)₂, Me₂SnCl₂(dmtp)₂, Et₂SnCl₂(dmtp)₂, Bu₂SnCl₂(dmtp), Ph₂SnCl₂(dmtp). The organotin:ligand stoichiometry goes from 1:2 to 1:1 by increasing the steric hindrance of the organic groups bound to tin. The compounds have been characterized by means of infrared, ¹¹⁹Sn Mössbauer and ¹H AND ¹³C NMR spectroscopy.The ligands presumably coordinate to tin classically through the nitrogen atom at the position 3. The 1:1 complexes adopt trigonal bipyramidal structures, with the organic groups on the equatorial plane and the ligand in the apical position. All-trans octahedral structures are inferred for the 1:2 complexes, except for Et₂SnCl₂(tp)₂, characterized by a skew-trapezoidal structure.¹¹⁹Sn Mössbauer measurements, at room temperature, in concomitance with DFT calculations, performed on isomeric structures of R₂SnCl₂(tp)₂ (R = Me, Et), allowed us to conclude that the all-trans octahedral coordination induces self-assembly in the solid state, possibly accomplished through π-π stacking interactions among the planar ligands coordinated to the organotin(IV) compound, while the skew-trapezoidal structure attributed to Et₂SnCl₂(tp)₂, induces the formation of monomeric adducts in the solid state.In vitro antimicrobial tests showed that [n-Bu₂SnCl₂(dmtp)] has interesting properties as anti Gram-positive and antibiofilm agent.     

Synthesis,physico-chemical characterization and bioevaluation of Ni(II), Pd(II), and Pt(II) complexes with 1-(o-tolyl)biguanide: Antimicrobial and antitumor studies

New complexes of type [M(tbg)₂]Cl₂ [tbg = 1-(o-tolyl)biguanide; M = Ni(II), Pd(II), and Pt(II)] were synthesized and characterized to develop new biologically active compounds. The features of the complexes were assigned from microanalytical and thermal data. The NMR, FT-IR, and UV-Vis spectra were established by comparison with HtbgCl. All complexes exhibit a square-planar geometry resulting from the chelating behavior of tbg. The HtbgCl and [Ni(tbg)₂]Cl₂ complexes were fully characterized by single-crystal X-ray diffraction. The HtbgCl species crystallize in the monoclinic C2/c spatial group, while the Ni(II) complex adopts an orthorhombic Pna2₁ spatial group. The structure is stabilized by a complex hydrogen bonds network. The in vitro antimicrobial assays revealed improved antimicrobial activity for complexes in comparison with the ligand against both planktonic and biofilm embedded microbial cells. The most efficient compound, showing the largest spectrum of antimicrobial activity, including Gram-positive and Gram-negative bacteria, as well as fungal strains, in both planktonic and biofilm growth states was the Pd(II) complex, followed by the Pt(II) complex. The Pt(II) compound exhibited the most significant antiproliferative activity on the human cervical cancer SiHa cell line, inducing a cell cycle arrest in the G2/M phase.     

In Vitro Anticancer Screening,Molecular Docking and Antimicrobial Studies of Triazole-Based Nickel(II) Metal Complexes

Herein we describe the synthesis of a series of nickel(II) complexes (C1–C3) with Schiff bases (HL1–HL3) derived from 4-amino-5-mercapto-3-methyl-1,2,4-triazole and ortho/meta/para-nitrobenzaldehyde having composition [Ni(L)₂(H₂O)₂]. The obtained ligands and their complexes were characterized using physico-chemical techniques viz., elemental analysis, magnetic moment study, spectral (electronic, FT-IR, 1H-NMR) and thermal analysis. The elemental analysis and spectral analysis revealed that Schiff bases behave as monoanionic bidentate ligands towards the Ni(II) ion. Whereas, the magnetic moment study suggested the octahedral geometry of all the Ni(II) complexes. The thermal behavior of the complexes has been studied by thermogravimetric analysis and agrees well with the composition of complexes. Further, the biological activities such as antimicrobial and antifungal studies of the Schiff bases and Ni(II) complexes have been screened against bacterial species (Staphylococcus aureus and Pseudomonas aeruginosa) and fungal species (Aspergillus niger and Candida albicans) activity by MIC method, the results of which revealed that metal complexes exhibited significant antimicrobial activities than their respective ligands against the tested microbial species. Furthermore, the molecular docking technique was employed to investigate the active sites of the selected protein, which indeed helped us to screen the potential anticancer agents among the synthesized ligand and complexes. Further, these compounds have been screened for their in vitro anticancer activity using OVCAR-3 cell line. The results revealed that the complexes are more active than the ligands.     

Efficient Direct Nitrosylation of α-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release

The reaction of rhenium α-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)₂(NO)(N-N)X]⁺ species (where X = halide). The complexes, accessible in a single step in good yield, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)₂(NO)(N-N)X]⁺ is that of a hard Re acid, probably due to the stronger π-acceptor properties of NO⁺ as compared to those of CO. The metal ion thus shows great affinity for π-basic ligands, which are consequently difficult to replace by, e.g., σ-donor or weak π-acids like pyridine. Attempts of direct nitrosylation of α-diimine fac-[Re(CO)₃]⁺ complexes bearing π-basic OR-type ligands gave the [Re(CO)₂(NO)(N-N)(BF₄)][BF₄] salt as the only product in good yield, featuring a stable Re-FBF₃ bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)₂(NO)(N-N)X]⁺ complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs.     

Structural Characterization,Antimicrobial Activity and BSA/DNA Binding Affinity of New Silver(I) Complexes with Thianthrene and 1,8-Naphthyridine

Three new silver(I) complexes [Ag(NO₃)(tia)(H₂O)]_n (Ag1), [Ag(CF₃SO₃)(1,8-naph)]_n (Ag2) and [Ag₂(1,8-naph)₂(H₂O)_1.2](PF₆)₂ (Ag3), where tia is thianthrene and 1,8-naph is 1,8-naphthyridine, were synthesized and structurally characterized by different spectroscopic and electrochemical methods and their crystal structures were determined by single-crystal X-ray diffraction analysis. Their antimicrobial potential was evaluated against four bacterial and three Candida species, and the obtained results revealed that these complexes showed significant activity toward the Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and the investigated Candida species with minimal inhibitory concentration (MIC) values in the range 1.56–7.81 μg/mL. On the other hand, tia and 1,8-naph ligands were not active against the investigated strains, suggesting that their complexation with Ag(I) ion results in the formation of antimicrobial compounds. Moreover, low toxicity of the complexes was detected by in vivo model Caenorhabditis elegans. The interaction of the complexes with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to evaluate their binding affinity towards these biomolecules for possible insights into the mode of antimicrobial activity. The binding affinity of Ag1–3 to BSA was higher than that for DNA, indicating that proteins could be more favorable binding sites for these complexes in comparison to the nucleic acids.     

Bioactive Tryptophan-Based Copper Complex with Auxiliary β-Carboline Spectacle Potential on Human Breast Cancer Cells: In Vitro and In Vivo Studies

Biocompatible tryptophan-derived copper (1) and zinc (2) complexes with norharmane (β-carboline) were designed, synthesized, characterized, and evaluated for the potential anticancer activity in vitro and in vivo. The in vitro cytotoxicity of both complexes 1 and 2 were assessed against two cancerous cells: (human breast cancer) MCF7 and (liver hepatocellular cancer) HepG2 cells with a non-tumorigenic: (human embryonic kidney) HEK293 cells. The results exhibited a potentially decent selectivity of 1 against MCF7 cells with an IC₅₀ value of 7.8 ± 0.4 μM compared to 2 (less active, IC₅₀ ~ 20 μM). Furthermore, we analyzed the level of glutathione, lipid peroxidation, and visualized ROS generation to get an insight into the mechanistic pathway and witnessed oxidative stress. These in vitro results were ascertained by in vivo experiments, which also supported the free radical-mediated oxidative stress. The comet assay confirmed the oxidative stress that leads to DNA damage. The histopathology of the liver also ascertained the low toxicity of 1.     

New Cobalt (II) Complexes with Imidazole Derivatives: Antimicrobial Efficiency against Planktonic and Adherent Microbes and In Vitro Cytotoxicity Features

Three novel Co(II) complexes of the type [Co(C₄H₅O₂)₂L₂] (where C₄H₅O₂ is methacrylate anion; L = C₃H₄N₂ (imidazole; HIm) (1), C₄H₆N₂ (2-methylimidazole; 2-MeIm) (2), C₅H₈N₂ (2-ethylimidazole; 2-EtIm) (3)) have been synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopic techniques, thermal analysis and single crystal X-ray diffraction. X-ray crystallography revealed for complexes (1) and (2) distorted trigonal bipyramid stereochemistry for Co(II), meanwhile for complex (3) evidenced that the unit cell comprises three molecular units with interesting structural features. In each unit, both stereochemistry adopted by metallic ion and coordination modes of carboxylate anions are different. The screening of antimicrobial activity revealed that Candida albicans planktonic cells were the most susceptible, with minimal inhibitory concentration (MIC) values of 7.8 μg/mL for complexes (1) and (2) and 15.6 μg/mL for complex (3). Complexes (1) and (2) proved to be more active than complex (3) against the tested bacterial strains, both in planktonic and biofilm growth state, with MIC and minimal biofilm eradication concentration (MBEC) values ranging from 15.6 to 62.5 μg/mL, the best antibacterial effects being noticed against Staphylococcus aureus and Pseudomonas aeruginosa. Remarkably, the MBEC values obtained for the four tested bacterial strains were either identical or even lower than the MIC ones. The cytotoxicity assay indicated that the tested complexes affected the cellular cycle of HeLa, HCT-8, and MG63 cells, probably by inhibiting the expression of vimentin and transient receptor potential canonical 1 (TRPC1). The obtained biological results recommend these complexes as potential candidates for the development of novel anti-biofilm agents.     

Studies on thermal,spectral, magnetic and biological properties of new Ni(II), Cu(II) and Zn(II) complexes with a bismacrocyclic ligand bearing an aromatic linker

Novel complexes of M₂LCl₄·nH₂O type (M:Ni, n = 4; M:Cu, n = 3 and M:Zn, n = 0; L: ligand resulted from 1,4-phenylenediamine, 3,6-diazaoctane-1,8-diamine and formaldehyde one-pot condensation) were synthesized and characterised by microanalytical, ESI–MS, IR, UV–Vis, ¹H NMR and EPR spectra, magnetic data at room temperature and molar conductivities as well. The electrochemical behaviour of complexes was investigated by cyclic voltammetry. Simultaneous TG/DTA measurements were performed in order to evidence the thermal behaviour of the obtained complexes. Processes such as water elimination, fragmentation and oxidative degradation of the organic ligand as well as chloride elimination occurred during thermal decomposition. The antimicrobial assays demonstrate that the compounds exhibited good antibacterial activity, especially against S. aureus and E. coli strains, the most active being the copper(II) complex, which also exhibited the most prominent anti-biofilm effect, suggesting its potential use for the development of new antimicrobial agents. The biological activity was correlated with log P _ow values. All complexes disrupt the membrane integrity of HCT 8 tumour cells.     

Synthesis,Identification, Computer-Aided Docking Studies,and ADMET Prediction of Novel Benzimidazo-1,2,3-triazole Based Molecules as Potential Antimicrobial Agents

2-azido-1H-benzo[d]imidazole derivatives 1a,b were reacted with a β-ketoester such as acetylacetone in the presence of sodium ethoxide to obtain the desired molecules 2a,b. The latter acted as a key molecule for the synthesis of new carbazone derivatives 4a,b that were submitted to react with 2-oxo-N-phenyl-2-(phenylamino)acetohydrazonoyl chloride to obtain the target thiadiazole derivatives 6a,b. The structures of the newly synthesized compounds were inferred from correct spectral and microanalytical data. Moreover, the newly prepared compounds were subjected to molecular docking studies with DNA gyrase B and exhibited binding energy that extended from −9.8 to −6.4 kcal/mol, which confirmed their excellent potency. The compounds 6a,b were found to be with the minimum binding energy (−9.7 and −9.8 kcal/mol) as compared to the standard drug ciprofloxacin (−7.4 kcal/mol) against the target enzyme DNA gyrase B. In addition, the newly synthesized compounds were also examined and screened for their in vitro antimicrobial activity against pathogenic microorganisms Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, Aspergillus niger, and Candida albicans. Among the newly synthesized molecules, significant antimicrobial activity against all the tested microorganisms was obtained for the compounds 6a,b. The in silico and in vitro findings showed that compounds 6a,b were the most active against bacterial strains, and could serve as potential antimicrobial agents.     

Syntheses and Structural Investigations of Penta-Coordinated Co(II) Complexes with Bis-Pyrazolo-S-Triazine Pincer Ligands,and Evaluation of Their Antimicrobial and Antioxidant Activities

Two penta-coordinated [Co(^MorphBPT)Cl₂]; 1 and [Co(^PipBPT)Cl₂]; 2 complexes with the bis-pyrazolyl-s-triazine pincer ligands ^MorphBPT and ^PipBPT were synthesized and characterized. Both ^MorphBPT and ^PipBPT act as NNN-tridentate pincer chelates coordinating the Co(II) center with one short Co-N(s-triazine) and two longer Co-N(pyrazole) bonds. The coordination number of Co(II) is five in both complexes, and the geometry around Co(II) ion is a distorted square pyramidal in 1, while 2 shows more distortion. In both complexes, the packing is dominated by Cl…H, C-H…π, and Cl…C (anion-π stacking) interactions in addition to O…H interactions, which are found only in 1. The UV-Vis spectral band at 564 nm was assigned to metal–ligand charge transfer transitions based on TD-DFT calculations. Complexes 1 and 2 showed higher antimicrobial activity compared to the respective free ligand ^MorphBPT and ^PipBPT, which were not active. MIC values indicated that 2 had better activity against S. aureus, B. subtilis, and P. vulgaris than 1. DPPH free radical scavenging assay revealed that all the studied compounds showed weak to moderate antioxidant activity where the nature of the substituent at the s-triazine core has a significant impact on the antioxidant activity.     

Mononuclear Tricoordinate Copper(I) and Silver(I) Halide Complexes of a Sterically Bulky Thiourea Ligand and a Computational Insight of Their Interaction with Human Insulin

Reaction of two equivalents of the bulky 1,3-bis(2,6-diethylphenyl)thiourea ligand (L) with MX (being M = Cu⁺, Ag+; and X = Cl⁻, Br⁻, I⁻) in acetonitrile afforded neutral complexes of the type [MXL₂] [CuClL₂].2CH₃CN (1a); [CuBrL₂].2CH₃CN (1b); [CuIL₂] (1c): [AgClL₂] (2a); [AgBrL₂] (2b) and [AgIL₂] (2c). The two aromatic groups in free ligand were found to be trans with respect to the thiourea unit, which was a reason to link the ligand molecules via intermolecular hydrogen bonding. Intramolecular hydrogen bonding was observed in all metal complexes. The copper complexes 1a and 1b are acetonitrile solvated and show not only intra- but also intermolecular hydrogen bonding between the coordinated thiourea and the solvated acetonitrile molecules. Silver complexes reported here are the first examples of structurally characterized tricoordinated thiourea-stabilized monomeric silver(I) halides. Molecular docking studies were carried out to analyze the binding modes of the metal complexes inside the active site of the human insulin (HI) protein. Analysis of the docked conformations revealed that the electrostatic and aromatic interactions of the protein N-terminal residues (i.e., Phe and His) may assist in anchoring and stabilizing the metal complexes inside the active site. According to the results of docking studies, the silver complexes exhibited the strongest inhibitory capability against the HI protein, which possesses a deactivating group, directly bonded to silver. All compounds were fully characterized by elemental analysis, NMR spectroscopy, and molecular structures of the ligand, and five out of six metal complexes were also confirmed by single-crystal X-ray diffraction.     

Nanoemulsions of Jasminum humile L. and Jasminum grandiflorum L. Essential Oils: An Approach to Enhance Their Cytotoxic and Antiviral Effects

Unprecedented nanoemulsion formulations (NE) of Jasminum humile and Jasminum grandiflorum essential oils (EO) were prepared, and examined for their cytotoxic and antiviral activities. NE characterization and stability examination tests were performed to ensure formula stability. The antiviral activity was determined against hepatitis A (HAV) and herpes simplex type-1 (HSV-1) viruses using MTT assay, while the cytotoxic potential was determined against liver (HepG-2), breast (MCF-7), leukemia (THP-1) cancer cell lines and normal Vero cells. Statistical significance was determined in comparison with doxorubicin as cytotoxic and acyclovir as antiviral standard drugs. GC-MS analysis indicated twenty four compounds in the EO of J. humile and seventeen compounds in the EO of J. grandiflorum. Biological investigations of pure EOs revealed weak cytotoxic and antiviral effects. Nevertheless, their NE formulations exhibited high biological value as cytotoxic and antiviral agents. NE formulations also showed feasible selectivity index for the viral-infected and cancer cells (especially HepG-2) than normal Vero cells. Both nanoemulsions showed lower IC₅₀ than standard doxorubicin against HepG-2 (26.65 and 22.58 vs. 33.96 μg/mL) and MCF-7 (36.09 and 36.19 vs. 52.73 μg/mL), respectively. The study results showed the dramatic effect of nanoemulsion preparation on the biological activity of EOs and other liposoluble phytopharmaceuticals.     

Arene Ruthenium(II) Complexes Bearing the κ-P or κ-P,κ-S Ph2P(CH2)3SPh Ligand

Neutral [Ru(η⁶-arene)Cl₂{Ph₂P(CH₂)₃SPh-κP}] (arene = benzene, indane, 1,2,3,4-tetrahydronaphthalene: 2a, 2c and 2d) and cationic [Ru(η⁶-arene)Cl(Ph₂P(CH₂)₃SPh-κP,κS)]X complexes (arene = mesitylene, 1,4-dihydronaphthalene; X = Cl: 3b, 3e; arene = benzene, mesitylene, indane, 1,2,3,4-tetrahydronaphthalene, and 1,4-dihydronaphthalene; X = PF₆: 4a–4e) complexes were prepared and characterized by elemental analysis, IR, ¹H, ¹³C and ³¹P NMR spectroscopy and also by single-crystal X-ray diffraction analyses. The stability of the complexes has been investigated in DMSO. Complexes have been assessed for their cytotoxic activity against 518A2, 8505C, A253, MCF-7 and SW480 cell lines. Generally, complexes exhibited activity in the lower micromolar range; moreover, they are found to be more active than cisplatin. For the most active ruthenium(II) complex, 4b, bearing mesitylene as ligand, the mechanism of action against 8505C cisplatin resistant cell line was determined. Complex 4b induced apoptosis accompanied by caspase activation.     

Characterization of copper(II) coordination compounds of 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine: the crystal structure of diaquatetrakis(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine-N3)-copper(II) hexafluorophosphate

Copper(II) coordination compounds of several CuA₂ salts (A = PF₆, BF₄, ClO₄, CF₃SO₃ or NO₃) with 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine (dmtp) as a ligand have been studied. The crystal structure of [Cu(dmtp)₄(H₂O)₂](PF₆)₂ is described. This compound is monoclinic, space group P2₁/c, a = 11.826(2) Å, b = 9.463(2) Å, c = 17.673(3) Å, β = 97.50(1)°, Z = 2, d_calc. = 1.66 Mg m⁻³, and has been refined to a final discrepancy factor (R) of 0.0382 based on 2316 reflections. The structure consists of PF⁻₆ anions and centrosymmetric mononuclear [Cu(dmtp)₄(H₂O)₂]²⁺ cations, Cu₂₊ being coordinated by four equatorial N(3)-bonded dmtp molecules with CuN = 2.019 and 2.050 Å, and by two axial water molecules with CuO = 2.650 Å. The water molecules form intramolecular hydrogen bonds with the dmtp N(4) atoms.     

Copper(II) complexes with 1,2,4-triazolo[1,5-a] pyrimidine and its 5,7-dimethyl derivative

Several Cu(II) complexes with 1,2,4-triazolo[1,5-a]pyrimidine (tp) and its 5,7-dimethyl derivative (dmtp) have been isolated and structurally characterized. Five of them are mononuclear and contain 1,10-phenanthroline (phen) or ethylenediamine (en) as auxiliary ligands, their formula being [Cu(H₂O)(phen)(tp)₂](ClO₄)₂ · H₂O, [Cu(H₂O)(phen)(dmtp)₂](ClO₄)₂, [Cu(NO₃)(H₂O)(phen)(tp)](NO₃), [Cu(H₂O)₂(en)(tp)₂](ClO₄)₂ and [Cu(H₂O)₂(en)(dmtp)₂](ClO₄)₂. In all these compounds the tp or dmtp ligand is monodentately coordinated via the nitrogen atom in position 3. The auxiliary ligand influences the coordination number, which is five when this ligand is phen and six when it is en whereas the number of triazolopyrimidine ligands linked to the metal seems to be influenced by the nature of the counteranion. A dinuclear compound with tp has also been isolated, its formula being [Cu₂(OH)(H₂O)_2.5(tp)₅](ClO₄)₃·(H₂O)_1.5, with both metal atoms linked by an hydroxydo group and by a tp bridging ligand, coordinated to one of the copper atoms via N3 and to the other via N4. This compound has several unusual features among the metal complexes with triazolopyrimidine derivatives: the presence of two different kinds of bridging moieties, the coexistence of bridging and terminal ligands and the formation of a N3–N4 bridge for a Cu(II) dinuclear compound for a derivative without exocyclic oxygen atoms.     

Synthesis,characterization, antimicrobial and diuretic study of Mg(II), Mn(II), Fe(II) and VO(II) complexes of chemotherapeutic importance

The synthesis, characterization and diuretic activity of four new biologically active complexes of Mg(II) and VO(II) with bidentate Schiff base ligand acetazolamide–salicylaldimine (L) obtained from the inserted condensation of 5-acetamido-1,3,4-thiadiazole-2-sulphonamide (acetazolamide) with salicylaldehyde in a 1:1 molar ratio have been reported. Using this bidentate ligand complexes of Mg(II), Mn(II), Fe(II) and VO(II) with general formula ML₂ have been synthesized. The synthesized complexes were characterized by several techniques using elemental analysis, FT-IR, electronic spectra, TGA, mass, particle size analysis and molar conductance measurements. The elemental analysis data suggest the stoichiometry to be 1:2 [M:L]. The molar conductance measurements suggest non-electrolytic nature of the complexes. Infrared spectral data agreed with the coordination to the central metal ion through deprotonated phenolic oxygen and azomethine nitrogen atoms. On the basis of spectral studies, octahedral geometry is suggested for Mg(II), Mn(II), Fe(II) and square pyramidal geometry is suggested for VO(II) complexes. The pure drug, synthesized ligand and metal(II) complexes were screened for their antimicrobial activities against Eschericia coli, Bacillus subtilis, Aspergillus niger and Aspergillus flavous. The results show that the metal complexes were more active than the ligand and pure drug against these microbial species as expected. The ligand and its Mg(II) complexes was screened for their diuretic activity also.     

Synthesis,Structure and Cytotoxic Properties of Copper(II) Complexes of 2-Iminocoumarins Bearing a 1,3,5-Triazine or Benzoxazole/Benzothiazole Moiety

A series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h, 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b, and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c were obtained by reacting of appropriate 2-iminocoumarin ligands L1a-h, L3a-b, and L5a-c with 3-fold molar excess of copper(II) chloride. The structure of these compounds was confirmed by IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction data (2f, 2g, 2h, and 6c). All the synthesized complexes were screened for their activity against five human cancer cell lines: DAN-G, A-427, LCLC-103H, SISO, and RT-4 by using a crystal violet microtiter plate assay and relationships between structure and in vitro cytotoxic activity are discussed. The coordination of 2-iminocoumarins with copper(II) ions resulted in complexes 2a-h, 4a-b, and 6a-c with significant inhibitory properties toward tested tumor cell lines with IC₅₀ values ranging from 0.04 μM to 15.66 μM. In comparison to the free ligands L1a-h, L3a-b, and L5a-c, the newly prepared Cu(II) complexes often displayed increased activity. In the series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h the most potent compound 2g contained a 4-phenylpiperazine moiety at position 6 of the 1,3,5-triazine ring and an electron-donating diethylamino group at position 7′ of the 2-iminocoumarin scaffold. Among the Cu(II) complexes of 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c the most active was benzoxazole-2-iminocoumarin 4b that also possessed a diethylamino group at position 7′ of the 2-iminocoumarin moiety. Moreover, compound 4b was found to be the most prominent agent and displayed the higher potency than cisplatin against tested cell lines.     

Synthesis of Novel N-Acylhydrazones and Their C-N/N-N Bond Conformational Characterization by NMR Spectroscopy

In this article, a synthesis of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides and their structural interpretation by NMR experiments is described in an attempt to explain the duplication of some peaks in their ¹H- and ¹³C-NMR spectra. Twenty new 6-methyl-1H-pyrazolo[3,4-b]quinoline substituted N-acylhydrazones 6(a–t) were synthesized from 2-chloro-6-methylquinoline-3-carbaldehyde (1) in four steps. 2-Chloro-6-methylquinoline-3-carbaldehyde (1) afforded 6-methyl-1H-pyrazolo[3,4-b]quinoline (2), which upon N-alkylation yielded 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetate (3). The hydrazinolysis of 3 followed by the condensation of resulting 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazide (4) with aromatic aldehydes gave N-acylhydrazones 6(a–t). Structures of the synthesized compounds were established by readily available techniques such as FT-IR, NMR and mass spectral studies. The stereochemical behavior of 6(a–t) was studied in dimethyl sulfoxide-d₆ solvent by means of ¹H NMR and ¹³C NMR techniques at room temperature. NMR spectra revealed the presence of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides as a mixture of two conformers, i.e., E_(C=N)(N-N) synperiplanar and E_(C=N)(N-N) antiperiplanar at room temperature in DMSO-d₆. The ratio of both conformers was also calculated and E_{(C=N) (N-N)} syn-periplanar conformer was established to be in higher percentage in equilibrium with the E_{(C=N) (N-N)} anti-periplanar form.     

Synthesis and Biological Evaluation of Novel Pyrimidine Amine Derivatives Bearing Bicyclic Monoterpene Moieties

A series of novel pinanyl pyrimidine amine derivatives (1e~1n) and camphoryl pyrimidine amine derivatives (2b~2f) bearing bicyclic monoterpene moieties were designed and synthesized from natural and renewable nopinone and camphor. All chemical structures of target compounds were characterized by ¹H NMR, ¹³C NMR and HRMS spectra analyses, and the antimicrobial activities were evaluated. The results indicated that most compounds showed considerable antibacterial and antifungal activities against Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Methicillin-Resistant Staphylococcus aureus (MRSA), Bacillus cereus and Candida albicans. Among them, 1f showed potent antibacterial activity against all tested bacteria, 1i exhibited excellent inhibition against Streptococcus pneumoniae (1 μg/mL) and Escherichia coli (1 μg/mL), which was better than the control drug amikacin (2 μg/mL). As to antifungal activity against Candida albicans (C. albicans), compound 1l showed comparable activity (16 μg/mL) to the control drug ketoconazole. Furthermore, five active compounds with better antimicrobial activities also showed anti-inflammatory potencies against mouse mononuclear macrophages leukemia cells (RAW). Especially, 1f (IC₅₀ = 1.37 μM) and 2f (IC₅₀ = 1.87μM) are more potent than the control drug aspirin (IC₅₀ = 1.91 μM).