Some bivalent metal complexes of Schiff bases containing N and S donor atoms

Schiff bases have been synthesized by the reaction of p-nitrobenzaldehyde, o-nitrobenzaldehyde and p-toluyaldehyde with 4-amino-5-mercapto-1,2,4-triazole. The ligands react with Co(II), Ni(II) and Zn(II) metals to yield (1:1) and (1:2) [metal:ligand] complexes. Elemental analyses, IR, ¹H NMR, electronic spectral data, magnetic susceptibility measurements, molar conductivity measurements and thermal studies have investigated the structure of the ligands and their metal complexes. The electronic spectral data suggests octahedral geometry for Co(II), Ni(II) and Zn(II). The antibacterial activities of the ligands and their metal complexes have been screened in vitro against three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Pseudomonas aeruginosa) organisms. The coordination of the metal ion had a pronounced effect on the microbial activities of the ligands and the metal complexes have higher antimicrobial effect than the free ligands.     

Synthesis,biological activities,and molecular docking studies of 2-mercaptobenzimidazole based derivatives

A new series of N-acylhydrazone derivatives of 2-mercaptobenzimidazole (2-MBI) has been synthesized through S-alkylation with 1-bromotetradecane and N-alkylation with ethyl-2-chloroacetate. The resulting ester was synthetically modified through hydrazine hydrate to acyl hydrazide which was condensed with aromatic aldehydes to afford the title N-acylhydrazones (4-17). Chemical structures of the newly synthesized compounds have been confirmed through mass, FT-IR and ¹HNMR techniques. In vitro free radical scavenging and α-glucosidase inhibition activities of the compounds were investigated with reference to the standard ascorbic acid and acarbose, respectively. Amongst the target compounds, 13 showed the highest inhibition in DPPH scavenging assay (IC₅₀ = 131.50 µM) and α-glucosidase inhibition potential (IC₅₀ = 352 µg/ml). We extended our investigations to explore the mechanism of enzyme inhibition and conducted docking analysis by using Molecular Operating Environment (MOE 2016.08). A homology model for α-glucosidase was constructed and validated using Ramachandran plot. Docking studies were also carried out on human intestinal α-glucosidases. In view of the importance of the nucleus involved, the synthesized compounds might find extensive medicinal applications as reported in the literature.     

Synthesis and antitubercular activity of novel Schiff bases derived from d-mannitol

Six Schiff base derivatives of d-mannitol, 1,6-dideoxy-1,6-bis-{[(E)-arylmethylidene]amino}-d-mannitol (6: aryl = XC₆H₄: X = o-, m- and p- Cl or NO₂), have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H₃₇Rv using the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. All three nitro derivatives exhibit significant activities: activities of (6d: X = o-NO₂), (6e: X = m-NO₂) and (6f: X = p-NO₂) are 12.5, 25.0 and 25.0 μg/mL, respectively. When compared with first line drugs, such as ethambutol, they can be considered as a good starting point to develop new lead compounds for the treatment of multidrug-resistant tuberculosis. Characterization of the new compounds 6 is generally achieved spectroscopically. The structure of compound 3 has been confirmed by X-ray crystallography.     

Antibacterial and antifungal metal based triazole Schiff bases

A new series of four biologically active triazole derived Schiff base ligands (L¹–L⁴) and their cobalt(II), nickel(II), copper(II) and zinc(II) complexes (1–16) have been synthesized and characterized. The ligands were prepared by the condensation reaction of 3-amino-5-methylthio-1H-1,2,4-triazole with chloro-, bromo- and nitro-substituted 2-hydroxybenzaldehyde in an equimolar ratio. The antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.     

Synthesis,characterization, biological and catalytic applications of transition metal complexes derived from Schiff base

A novel series of Cu(II), Ni(II), Zn(II), Co(II), and Cd(II) complexes have been synthesized from the Schiff base. Structural features were determined by analytical and spectral techniques like IR, ¹H NMR, UV–vis, elemental analysis, molar electric conductibility, magnetic susceptibility and thermal studies. The complexes are found to be soluble in dimethylformamide and dimethylsulfoxide. Molar conductance values in dimethylformamide indicate the non-electrolytic nature of the complexes. Binding of synthesized complexes with calf thymus DNA (CT DNA) was studied. There is significant binding of DNA in lanes 2, 3, and 5. Lanes 4 and 6 are showing more florescence when compared to the control indicating that these molecules are strongly bound to the DNA by inserting themselves between the two stacked base pairs and exhibiting their original property of fluorescence. Angiogenesis study has revealed that the compounds B-2, B-4 and B-5 have potent antitumor efficacy and activation of antiangiogenesis could be one of the possible underlying mechanisms of tumor inhibition.     

Antibacterial Co(II), Ni(II), Cu(II) and Zn(II) Complexes of Schiff bases Derived from Fluorobenzaldehyde and Triazoles

Antibacterial Schiff bases derived from 1,2,4-triazoles as well as their metal complexes incorporating cobalt(II), nickel(II), copper(II) and zinc(II) have been synthesized and characterized. Physico-chemical studies suggest that an octahedral geometry for the cobalt(II), nickel(II) and zinc(II)and square-planer geometry for the copper(II) complexes. These complexes have been screened for antibacterial activity against three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Pseudomonas aeruginosa) bacterial strains, and results compared with the activity of the free ligands. The metal complexes were found to be more potent against one or more bacterial strains than the free ligands.     

Synthesis, characterization and biological studies of organotin(IV) complexes with hydrazone ligand

Four organotin(IV) complexes with general formula [RSnCl_n−1(TCB)] [R = Ph₂, n = 2 (2); R = Me, n = 3 (3); R = Bu, n = 3 (4); R = Ph, n = 3 (5)] have been synthesized by direct reaction of thiophene-2-carboxaldehyde benzhydrazone ligand [HTCB, (1)], base and organotin(IV) chloride in absolute methanol under N₂ atmosphere. All organotin(IV) complexes were characterized by elemental analyses, molar conductivity, UV-Vis, FT-IR, ¹H and ¹³C NMR spectral studies. Among them, diphenyltin(IV) complex (2) has also been characterized by X-ray crystallography diffraction analyses. The cytotoxicity of the hydrazone ligand as well as its organotin(IV) complexes (2-5) were determined with Artemia salina. While no-choice bioassay was employed on Coptotermes sp. to evaluate the termiticidal effect of all the complexes. Besides, the ligand (1) and its organotin(IV) complexes (2-4) were also tested against five types of bacteria namely Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi.     

Synthesis, characterization and antiproliferative activity of metal complexes with the Schiff base derived from the condensation 1:2 of 2,6-diformyl-4-methylphenol and 5,6-diamino-1,3-dimethyluracil

A series of mononuclear complexes with Co(II), Ni(II), Cu(II), Zn(II), Hg(II), Mo(VI) and Pd(II) containing the ligand derived from the 1:2 condensation of 2,6-diformyl-4-methylphenol and 5,6-diamino-1,3-dimethyluracil (hereafter denoted as BDFDAAU) were synthesized. The complexes were characterized by elemental analysis, thermogravimetry (TG) and differential scanning calorimetry (DSC), IR, (1)H, (13)C and (15)N NMR, UV-visible-near IR (UV-VIS-NIR), EPR and magnetic measurements. The deprotonated ligand in the phenolic oxygen shows a symmetric tridentate coordination mode through the two azomethine nitrogen atoms and the phenolic oxygen atom whereas the coordination of the neutral ligand takes place through the phenolic oxygen atom and one azomethine nitrogen atom. In the Mo(VI) complex, the ligand is bideprotonated in the phenolic oxygen and an amino group from one uracil unit; so, the coordination mode changes again into an asymmetric way: phenolic oxygen atom, one azomethine nitrogen atom and the nitrogen atom from the deprotonated amino group. The antiproliferative behaviour against the five human tumor cell lines (human neuroblastoma NB69, human breast cancer MCF-7 and EVSA-T, human glioma H4 and human bladder carcinoma cell line ECV) suggested a modulator behaviour, according to the concentration, of cell growth due to their estrogen-like characteristics.     

Antifungal properties of Schiff bases of chitosan, N-substituted chitosan and quaternized chitosan

Schiff bases of chitosan, N-substituted chitosan, and quaternized chitosan were synthesized and their antifungal properties were analyzed against Botrytis cinerea Pers. (B. cinerea pers.) and Colletotrichum lagenarium (Pass) Ell.et halst (C. lagenarium (Pass) Ell.et halst) based on the method of D. Jasso de Rodríguez and co-workers. The results showed that quaternized chitosan had better inhibitory properties than chitosan, Schiff bases of chitosan, and N-substituted chitosan.     

Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I,II, IV,VII, and IX activators

A series of 20 histamine Schiff base was synthesised by reaction of histamine, a well known carbonic anhydrase (CA, E.C 4.2.2.1.) activator pharmacophore, with substituted aldehydes. The obtained histamine Schiff bases were assayed as activators of five selected human (h) CA isozymes, the cytosolic hCA I, hCA II, and hCA VII, the membrane-anchored hCA IV and transmembrane hCA IX. Some of these compounds showed efficient activity (in the nanomolar range) against the cytosolic isoform hCA VII, which is a key CA enzyme involved in brain metabolism. Moderate activity was observed against hCA I and hCA IV (in the nanomolar to low micromolar range). The structure–activity relationship for activation of these isoforms with the new histamine Schiff bases is discussed in detail based on the nature of the aliphatic, aromatic, or heterocyclic moiety present in the aldehyde fragment of the molecule, which may participate in diverse interactions with amino acid residues at the entrance of the active site, where activators bind, and which is the most variable part among the different CA isoforms.     

Synthesis, structural characterization, antiradical and antidiabetic activities of copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and beta-alanine

A series of copper(II) and zinc(II) complexes involving a tridentate O,N,O'-donor Schiff base derived from salicylaldehyde and beta-alanine {i.e. N-salicylidene-beta-alanine(2-), (L)}, having the composition [Cu(2)(L)(2)(H(2)O)].H(2)O (1), [Cu(L)(H(2)O)](n) (2), and [Zn(L)(H(2)O)](n) (3), have been prepared and characterized by elemental analyses, UV-visible (UV-VIS), FT-IR and ESI-MS spectra, and thermal analyses. Complexes 1 and 2 have been investigated by single crystal X-ray analysis and also by temperature dependent magnetic susceptibility measurements (294-80K). All prepared complexes have been evaluated by the antiperoxynitrite activity assay and alloxan-induced diabetes model. The significant antioxidant and antidiabetic activities have been found in the case of both copper(II) complexes 1 and 2. In spite of first two complexes, the zinc(II) complex 3, as well as the potassium salt of the ligand (KHL) showed only insignificant protective effect against the tyrosine nitration in vitro.     

Synthesis, structural characterisation and biological studies of new mononuclear platinum(II) complexes with sterically hindered heterocyclic ligands

Three novel cisplatin analogues were synthesized, designed according to an approach which violates the “classical” structure-activity relationship, by replacing the diamine ligands with a planar N donor heterocycle giving a sterically hindered complex. Moreover, the sterical hindrance of antitumor drug candidates potentially makes them less susceptible to deactivation by sulphur-containing proteins and helping to overcome resistance mechanisms. The resulting mononuclear complexes of sterically hindered polidentate heterocyclic N ligands [PtCl(bbp)]Cl (1) [bbp = 2,6-bis(2-benzimidazolyl)pyridine], [PtCl₂(dptdn)](H₂O) (2) [dptdn = sodium 5,6-diphenyl-3-(2′-pyridyl)-1,2,4-triazine-4″,4″′-disulfonate] and [(dptdn)(dpt)Pt]Cl₂(H₂O) (3) [dpt = 5,6-diphenyl-3-(2′-pyridyl)-1,2,4-triazine] have been prepared and structurally characterised. Both neutral and ionic complexes are present, with monofunctional (1) and bifunctional Pt(II) moieties (2) and coordinatively saturated Pt(II) ions in the mixed ligand complex (3), whose size and shape enable them to behave as novel scaffolds for DNA binding. All complexes were tested “in vitro” for their biological activity on human HT29 colorectal carcinoma and HepG2 hepatoma cells. The complexes (1) and (3), endowed with a positive charge, showed a potent cytotoxic activity and reduced cell viability with an efficacy higher than that of cisplatin; whilst the neutral bifunctional compound (2) was inactive. IC50 values have been calculated for the active compounds. The cytotoxic effects were confirmed by the accumulation of treated cells in subG0/G1 phase of cell cycle, by the loss of mitochondrial potential (Δψ_m) and by the chromatin condensation or fragmentation observed by means of fluorescence microscopy after Hoechst 33258 nuclear staining. A study on intracellular platinum uptake in HT29 cell line has been also performed and data obtained strongly suggest that the cytotoxicity of new tested complexes reported in this work is based on a different pharmacodynamic pattern with respect to cisplatin.     

Synthesis,antimicrobial and anti-biofilm activities of novel Schiff base analogues derived from methyl-12-aminooctadec-9-enoate

A novel library of Schiff base analogues (5a–q) were synthesized by the condensation of methyl-12-aminooctadec-9-enoate and different substituted aromatic aldehydes. The synthesized compounds were thoroughly characterized by spectroscopic techniques (FT-IR, ¹H NMR, ¹³C NMR, ESI-MS and HRMS). The Schiff base analogues with different substitutions were screened for in vitro antibacterial activity against 7 different bacterial strains. Among these, the compounds with electron withdrawing substituent, namely chlorine (5a) and electron donating substituents, namely hydroxy (5n) and methoxy (5o), were found to exhibit excellent to good antimicrobial activities (MIC value 9–18 μM) against Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS-16 MTCC 2940 and Bacillus subtilis MTCC 121. The products were also screened for anti-biofilm and MBC (Minimum Bactericidal Concentration) activities which exhibited promising activities.     

Synthesis, crystal structure and photo-induced DNA cleavage activity of ternary copper(II) complexes of NSO-donor Schiff bases and NN-donor heterocyclic ligands

New ternary copper(II) complexes [CuLⁿB](ClO₄) (1-3), where HLⁿ is the NSO donor Schiff base derived from the condensation of 2-mercaptoethylamine hydrochloride with salicylaldehyde (HL¹) or 2-hydroxy-3-methoxybenzaldehyde (HL²) and B is NN-donor heterocyclic base like 2,2′-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2) or 2,9-dimethyl-1,10-phenanthroline (dmp, 3), are prepared, structurally characterized by X-ray crystallography and their DNA cleavage activity studied. The complexes show distorted square-pyramidal (4 + 1) CuN₃OS coordination geometry in which the NSO-donor Schiff base is bonded at the basal plane and the NN-donor heterocyclic base displays axial-equatorial mode of bonding [Cu-S distance: ∼2.4 Å]. The one-electron paramagnetic (μ_eff = ∼1.9 μ_B) complexes display axial EPR spectra in DMF glass at 77 K giving g_∥ = ∼2.2 (A_∥ = 162 G) and g_⊥ = ∼2.0, indicating {d_x²-y²}¹ ground state. The complexes exhibit visible spectral d-d band in MeCN near 650 nm and two charge transfer bands near 400 nm. Complexes 1 and 2 display quasireversible cyclic voltammetric response in DMF-Tris buffer (1:4 v/v, pH 7.2) for the Cu(II)/Cu(I) couple at ca. −0.1 V vs. SCE. Complex 3 exhibits an irreversible reduction process forming [Cu^I(dmp)₂]⁺. Binding of 1-3 to calf thymus DNA shows the relative order: 2 (phen) ? 3 (dmp) > 1 (bpy). Complex 2 efficiently cleaves supercoiled pUC19 DNA in the presence of mercaptopropionic acid (MPA) forming hydroxyl radical or on irradiation with light of 312, 532 and 632.8 nm wavelength in a type-II process. Complexes 1 and 3 are cleavage inactive.     

Synthesis and aggregation phenomena of multifunctional Schiff bases and Ni(II) complexes: an X-ray investigation

Multifunctional Schiff base ligands Lⁿ, namely the tetradentate N,N^′-bis[2-hydroxy-5-(azopyridine)benzylidene]propylendiamine and the bidentate N-dodecyl-5-(azopyridine)salicylaldimine, both containing a flexible azo spacer, a metallation site and a terminal pyridine group, were synthetised and fully characterised. Mesogenic structures, analysed by polarised optical microscopy, DSC and powder X-ray diffraction, were obtained from self-assembly of the mono or bifunctional hydrogen-bond acceptors Lⁿ with carboxylic acid donors. Ni(II) mono and bis-chelate, four- and six-coordinated, Lⁿ derivatives were synthetised. The octahedral structure of the [Ni(py)₂(L²)₂] complex was confirmed by single crystal X-ray analysis. H-bonded self-assembly of Ni(II) complexes and carboxylic acids results in the formation of supramolecular networks whose structure and thermal stability were studied by DSC and powder X-ray diffraction analysis at variable temperatures.     

Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases

To discover multifunctional agents for the treatment of Alzheimer’s disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC₅₀ values 4.12 ± 0.01, 8.12 ± 0.01 and 8.41 ± 0.06 μM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC₅₀ = 0.85 ± 0.0001 μM). Three compounds 13, 24 and 3 having IC₅₀ values 6.51 ± 0.01, 9.22 ± 0.07 and 37.82 ± 0.14 μM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC₅₀ = 0.04 ± 0.0001 μM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed.     

Some biologically active oxovanadium(IV) complexes of triazole derived Schiff bases: their synthesis,characterization and biological properties

A series of biologically active oxovanadium(IV) complexes of triazole derived Schiff bases L₁–L₅ have been synthesized and characterized by their physical, analytical, and spectral data. The synthesized ligands potentially act as bidentate, in which the oxygen of furfural and nitrogen of azomethine coordinate with the oxovanadium atom to give a stoichiometry of vanadyl complexes 1:2 (M:L) in a square-pyramidal geometry. In vitro antibacterial and antifungal activities on different species of pathogenic bacteria (E. coli, S. flexneri, P. aeruginosa, S. typhi, S. aureus, and B. subtilis) and fungi (T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glabrata) have been studied. All compounds showed moderate to significant antibacterial activity against one or more bacterial strains and good antifungal activity against most of the fungal strains. The brine shrimp bioassay was also carried out to check the cytotoxicity of coordinated and uncoordinated synthesized compounds.     

Synthesis, characterization and antifungal activity of a series of manganese(II) and copper(II) complexes with ligands derived from reduced N,N'-O-phenylenebis(salicylideneimine)

A series of manganese(II) and copper(II) complexes with reduced Schiff bases derived from o-phenylenediamine has been prepared and characterized by elemental analysis, TG measurements, ESR, magnetic measurements, FTIR, UV-Visible spectra and conductivity. These complexes were found to be [MnL(H2O)n] and [CuL](H2O)n species with n=0-2. Their antifungal activity was evaluated on different human fungi including yeasts of the Candida genus (C. albicans, C. glabrata, C. tropicalis and C. parapsilopsis) some opportunistic moulds belonging to the Aspergillus (A. fumigatus, A. terreus and A. flavus), Scedosporium genus (S. apiospermum and S. prolificans) and some dermatophytes (M. gypseum, M. persicolor, T. mentagrophytes, M. canis and T. tonsurans). The manganese complexes showed a significant growth inhibition of the dermatophytes tested and fungi of the genus Scedosporium. This is very interesting as these fungi are usually poorly susceptible to current antifungal including Amphotericin B and Itraconazole chosen as reference in this study.     

Synthesis,biological evaluations and computational studies of N-(3-(-2-(7-Chloroquinolin-2-yl)vinyl) benzylidene)anilines as fungal biofilm inhibitors

In the present investigation, new chloroquinoline derivatives bearing vinyl benzylidene aniline substituents at 2nd position were synthesized and screed for biofilm inhibitory, antifungal and antibacterial activity. The result of biofilm inhibition of C. albicans suggested that compounds 5j (IC₅₀ value?=?51.2?μM) and 5a (IC₅₀ value?=?66.2?μM) possess promising antibiofilm inhibition when compared with the standard antifungal drug fluconazole (IC₅₀?=?40.0?μM). Two compounds 5a (MIC?=?94.2?μg/mL) and 5f (MIC?=?98.8?μg/mL) also exhibited good antifungal activity comparable to standard drug fluconazole (MIC?=?50.0?μg/mL). The antibacterial screening against four strains of bacteria viz. E. coli, P. aeruginosa, B. subtilis, and S. aureus suggested their potential antibacterial activity and especially all the compounds except 5g were found more active than the standard drug ciprofloxacin against B. subtilis. To further gain insights into the possible mechanism of these compounds in biofilm inhibition through the agglutinin like protein (Als), molecular docking and molecular dynamics simulation studies were carried out. Molecular modeling studies suggested the clear role in inhibition of this protein and the resulting biofilm inhibitory activity.