Available via license: CC BY-NC 3.0
Content may be subject to copyright.
Antifungal Activities of Copper(II) with Biosensitive Macrocyclic Schiff Base Ligands Derived from 4-Aminoantipyrine Derivatives
Mycobiology
Abstract and Figures
Novel copper(II) complexes have been synthesized from the macrocyclic Schiff bases derived from Knoevenagel condensed β-ketoanilides (obtained by the condensation of acetoacetanilide and substituted benzaldehydes), 4-aminoantipyrine and o-phenylene diamine. The structural features have been determined from their analytical and spectral data. All the Cu(II) complexes exhibit square planar geometry. Their high molar conductance values support their 1 : 2 electrolytic nature. The magnetic moment data provide evidence for the monomeric nature of the complexes. The X-band ESR spectra of the [CuL(1)](OAc)2 in DMSO solution at 300 and 77 K were recorded and their salient features are reported. The in vitro biological screening effects of the investigated compounds were tested against the bacterial species Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa and fungal species Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataicola and Candida albicans by well diffusion method. A comparative study of inhibition values of the Schiff bases and their complexes indicate that complexes exhibit higher antimicrobial activity than the Schiff bases. Copper ions proved to be essential for the growth-inhibitor effect. The extent of inhibition appeared to be strongly dependent on the initial cell density and on the growth medium.
Figures - available via license: Creative Commons Attribution-NonCommercial 3.0 Unported
Content may be subject to copyright.
... In Figures 6 and 7, the UV spectrum of ligand (L) mostly shows three intense absorption peaks at 37543 cm -1 , 34482 cm -1 and 33456 cm -1 which belong to π→π*, and n→π* and C.T, respectively, (See Table 4 [13], (See Table 4, Figure 5) for an octahedral geometry [28]. Moreover, the magnetic moment µeff. of this complex in the sold state (4.50 B.M) suggests a low-spin octahedral geometry [29]. ...
... The measured magnetic moment µeff. of Mn(II) complex is (5.18 B.M) which corresponds to five unpaired electronic indicates high-spin octahedral environment[28], ( ...
AZO complexes synthesized by binding metal ions as Mn(II), Co(II), Ni(II) and Cu(II), with the ligand (L) [ethyl 4-((E)-(5-oxo-1-(((1E,2E)-3-phenylallylidene)amino)-2-thioxo-2,5-dihydro-1H-imidazol-4-yl)diazenyl)benzoate] was prepared from three steps ,first step preparation Schiff base product of condensation reaction by reaction Thiosemicarbazide with cinnamaldeyde, second step preparation the Imidazole ring close by reaction ligand 1 with chloroethylacetate, finally preparation Azo ligand(Diazanium compound) by reaction ligand 2 with benzocain. Characterized the ligands and complexes in their solid state using the elemental micro analysis (C.H.N.S), flame atomic absorption. UV-vis spectroscopy, FT-IR, magnetic susceptibility measurements, Mass spectrum, 1H-NMR spectra and electrical molar conductivity. These techniques produced comparable results with those obtained for the solid complexes. From the data of all techniques, octahedral geometry was proposed for Mn(II), Co(II), Ni(II) and Cu(II) complexes.
... [25][26][27][28] The ortho-phenylenediamine derivatives are Schiff bases recognized for their therapeutic value as they were reported to have anti-inflammatory, analgesic, antiviral, antitumor, antifungal and antibacterial properties. [29][30][31][32][33][34] Molecular modeling is a recognized computational tool to aid early drug discovery and development. It is used to generate ideas of a compounds or macromolecules 3D conformation, protein-ligand interactions, and allows forecasts about biological activities. ...
A series of new ortho-phenylenediamine derivatives has been designed. The crystal structure of the post fusion core of 2019-nCoV S2 subunit and perfusion 2019-nCoV spike glycoprotein with a single receptor-binding domain was used as target protein for molecular docking of ortho- phenylenediamine derivatives. in addition a protein-ligand interaction analysis was performed using Auto Dock 4.2 software. Based on the docking score and after three-dimensional similarity analysis, NHM7[(10,10'-((1E,1'E)-(1,2-Phenylenebis(azanylylidene)) bis(methanylylidene)) bis(anthracen-9(8aH)-one)] had the highest binding energy. The calculated binding energy of ortho- phenylenediamine indicates effective binding of proposed inhibitors to the fusion core of 2019-nCoV S2 subunit and pre-fusion 2019-nCoV spike glycoprotein with a single receptor-binding domain.
... Gopalakrishnan et al. [20] synthesized a series of Schiff base ligands by treating 4-aminoantipyrine with a β-ketoanilide motifs obtained from the reaction of acetoacetanilide with p-hydroxybenzaldehyde, benzaldehyde and p-nitrobenzaldehyde respectively. The Schiff base ligands were treated with o-phenylene diamine to obtain three novel macrocyclic ligands, which were then reacted with copper acetate to produce the complexes 28-30. ...
Transition metal complexes of 4-aminoantipyrine derivatives have been gaining great interest due
to their rich coordination chemistry and potential applications in the field of pharmaceutical science. The
presence of a free amine and a cyclic ketone functionality makes 4-aminoantipyrine an attractive amphoteric
substrate for Schiff base formation. Varieties of aldehydes/ketones or amines of versatile steric, electronic and
functional nature could be condensed with the 4-aminoantipyrine motif to obtain the ligand systems of multidenticity
and diverse coordination behaviour. The transition metal complexes obtained from these ligand systems
exhibit unique structural and functional properties. This review compiles the important transition metal
complexes developed from the Schiff base derivatives of 4-aminoantipyrine, and their utility as antibacterial
and antifungal agents. Rationale of the strategies involved in the development of highly potential antimicrobial
agents is discussed.
... Thus, it has been reported that the SARS-CoV main protease has 96.1% homology with the COVID-19 main protease and therefore may be used as a homologous target for the screening of 2-(4-(aminomethyl)phenyl)isoindoline-1,3-dione Schiff base derivatives that could inhibit the proliferation and replication of COVID-19 [12][13][14][15]. The 2-(4-(aminomethyl)phenyl)isoindoline-1,3-dione Schiff base derivatives are Schiff bases recognized for their therapeutic value as they were reported to have antiinflammatory, analgesic, antiviral, antitumor, antifungal and antibacterial properties [16][17][18][19][20][21]. Molecular modeling is a recognized computational tool to aid early drug discovery and development. ...
The 2019 coronavirus (COVID-19) pandemic is spreading worldwide, with a spectacular increase in death missing any effective therapeutic treatment up to now. Molecular docking is a recognized computational tool to assist in early drug discovery and development. Molecular docking analysis was carried out using 2-(4-(aminomethyl)phenyl)isoindoline-1,3-dione Schiff base conjugates with SARS-CoV-2 protease enzyme and COVID-19 main protease in apo form (6M03). The compounds with the best normalized docking scores to protease enzyme (6LU7) were ARG3 (-8.1 kcal/mole), ARG7 (-8.1 kcal/mole) and ARG6 (-8.0 kcal/mole). The best docking ligands for main protease in apo form (6M03) were ARG7 (-8.7 kcal/mole), ARG6 (-8.6 kcal/mole) and ARG3 (-8.4 kcal/mole). The structural similarity between these conjugates inspired us to perform in silico studies to check their possible binding interactions with essential SARS-CoV-2 proteins. These studies provide insight into the potential binding between Schiff base derivatives and SARS-CoV-2 proteins to provide an insight for finding an effective therapy. Finally, ADMET calculations were performed for the Schiff base compounds to predict their pharmacokinetic profiles.
... Nevertheless, copper and zinc ions are very toxic to unicellular organisms and mammalian cells in vitro. Thus, the antibacterial activity of these ions and their oxide nanoparticles has been previously researched (Ishida et al. 2019;Borovansky et al. 1989;Diaz-Visurraga et al. 2011;Solioz et al. 2018;Ishida et al. 2017;Gopalakrishnan et al. 2009). The antibacterial activities of Cu 2+ ions against E. coli and S. aureus were intensively researched. ...
Although it is unclear how Zn2+ cooperates with Cu2+ in synergistic antibacterial activity, a 1:10 ratio of Cu2+/Zn2+ atoms and ethylenediaminetetra-acetic acid and urea ligands can be used to form a chelation complex containing Cu2+ and Zn2+. This study investigated the effects of the combination of Cu2+ and Zn2+ in chelation with EDTA and urea. The results were compared with the outcomes of either copper or zinc alone against gram-negative Escherichia coli (E. coli) and gram-positive Staphylococcus aureus (S. aureus) bacteria. The antibacterial activity was determined through MICs, disc diffusion method, and bacterial cell growth curves. In addition, bacterial destruction by this chelation complex has been observed through SEM images. The presence of copper ion and zinc ion inside the bacterial cells has been proved through EDS measurements. The obtained results allowed us to draw conclusions that the use of both Cu2+ and Zn2+ in a chelation complex with EDTA and urea enhances the antimicrobial activity against these bacteria. The bacterial inhibition of this complex was stronger than that of Cu2+ alone chelated with EDTA or CuSO4 solution by approximately 100-fold for S. aureus and 20-fold for E. coli.
... Nystatin was used as standard medicine. When Table 3 is examined, it is understood that the complex shows a stronger activity against fungi than bacteria [35]. Thus, the complex showed an inhibition close to nystatin against both selected fungi (p < 0.05). ...
The copper(II) complex (NMPAAP-Cu) of 1,5-dimethyl-4-(((1-methyl-1H-pyrrol-2-yl)methylene)amino)-2-phenyl-1,2-dihydro-3H-pyrazole-3-one (NMPAAP) was synthesized and analyzed by elemental analysis, magnetic susceptibility molar conductivity, thermal analysis, and defined spectral features using MS, IR, UV-vis, ¹H, ¹³C NMR. In vitro biological activity of the complex was also investigated. Antimicrobial potency was evaluated by Disc Diffusion Method. Antioxidant activity was investigated by using DPPH radical scavenging and metal chelating activity tests. The complex exhibited a dose-dependent increase in its antioxidant capacity. The in vitro cytotoxic and anticancer potentials were evaluated in the human breast cancer cell line MCF-7. Data showed that NMPAAP-Cu significantly decreased the cell viability of MCF-7 cells in a concentration-dependent manner. AO/EB staining showed that the complex significantly increased apoptosis in MCF-7 cells. 50 µM NMPAAP-Cu also inhibited the migration of MCF-7 cells revealed in the wound healing assay. The study results indicated that the NMPAAP-Cu showed very high anticancer activity against MCF-7 carcinoma cells.
... in the present complex, the α 2 is 0.47, which is almost equal to 0.5 and < 1 indicating the covalent nature of the complex [20]. Thermal stability: Thermal stability of [Cu(SB)2(NO2)2] complex shows a three-step decomposition process in the range of 192-580 ºC, respectively; the weight loss of 37.56% at 277.9 ºC was observed, which corresponds to the removal of one Schiff base moiety from the coordination sphere. ...
The reaction of Cu(NO3)2·3H2O and Ni(NO3)2·6H2O with E-N-(4-isopropylbenzylidine)isonicotinohydrazide derived from isonicotinic acid hydrazide with 4-isopropyl benzaldehyde were synthesized and characterized structurally by physico-chemical and spectral techniques. The metal-ligand ratio in metal complexes is in the order of metal:ligand1:ligand2 (1:1:1) indicating the formulae of the complexes as [M(SB)2(NO2)2] (where M = Cu2+ & Ni2+, SB = C16H17N3O). The magnetic moment and electronic spectral data suggest tetragonal geometry for Cu(II) complex and octahedral geometry for Ni(II) complex around the central metal ions. The FT-IR and Far-IR spectroscopic data suggest the bidentate nature of ligand. The geometry of the Cu(II) complex and its covalence is confirmed by EPR spectral data. The Thermal decomposition of metal complexes has been identified using thermogravimetric analysis. The conductometric measurements proved the non-electrolytic behaviour of all the compounds. With the help of the agarose gel electrophoresis method, the DNA cleavage studies of Schiff base metal complexes were predicted. Also, the in-vitro antioxidant activity of Cu(II) complex was determined by a free radical scavenging assay.
... Taking into account their possible biological activities, new coordination compounds with first row transition metals have been relentlessly investigated. Nowadays, particular attention is directed towards complexes with copper, cobalt, nickel, manganese or zinc, all of them possessing prominent biological effects [46,47,49,52,53]. ...
After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs’ biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs’ properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.
The World is facing an epidemic of various diseases caused by viruses, bacteria, and fungi. Apart from it, cancer, malaria, and diabetes are some major health problems. So, a need arises to discover novel molecules that can be used as therapeutic drugs for several diseases, including cancer and diabetes. Macrocyclic Schiff base (MSB) transition metal complexes are popularly studied organometallic compounds due to their vast biological applications in treating infectious diseases and various health problems. This attracts the researchers to the Chemistry of Schiff base metal complexes in pharmaceutical applications and areas like biochemical, bio-inorganic, environmental, industrial, photochemical, photophysical, photoelectronic etc. So, the Novel synthesis of Schiff base metal complexes will design and develop more effective therapeutic drugs. Even though the topic is quite old and exploited, many researchers are still globally working to find new MSB complexes and their applications. Based on the above considerations, we have reviewed the pharmaceutical properties of MSB transition metal complexes synthesized in the last two decades.
In this research, nine novel heterocyclic Schiff base derivatives (10-18) bearing an aryl sulfonate moiety were designed, synthesized for the first time, and characterized. Then, their inhibitory effects on acetyl-and butyrylcholinesterase (AChE and BChE) were investigated in vitro conditions. Moreover, their antioxidant activities were examined by DPPH and ABTS methods. The results indicated that some of the tested molecules had varying enzyme inhibition and antioxidant activities. We determined that compounds 8, 9, 14, 17, and 18 indicated inhibitory effects with IC 50 values ranging from 89.30 to 111.28 μM against BChE, respectively compared to standard compound galanthamine (IC 50 = 125.88 μM). On the other hand, of the molecules tested, only compound 5 (IC 50 = 36.64 μM) displayed inhibitory activity higher than galanthamine against AChE. In DPPH assay, compounds 15 (IC 50 = 161.93 μM), 16 (IC 50 = 191.76 μM) and 17 (IC 50 = 107.55 μM) showed higher antioxidant activity than BHT (IC 50 = 203.50 μM). On the other hand, it was determined in ABTS assay that Schiff bases 10-17 (except for compound 18) indicated higher antioxidant activity than BHT.
The reactions of ruthenium(II) complexes, [RuHCl(CO)(PPh3)2(B)] [B = PPh3, pyridine (py) or piperidine (pip)], with bidentate Schiff base ligands derived by condensing salicylaldehyde with aniline, o-, m- or p-toluidine have been carried out. The products were characterised by analytical, i.r., electronic, 1H-n.m.r. and 31P-n.m.r. spectral studies and are formulated as [RuCl(CO)(L)(PPh3)(B)] (L = Schiff base anion; B = PPh3, py or pip). An octahedral structure has been tentatively proposed for the new complexes. The Schiff bases and the new complexes were tested in vitro to evaluate their activity against the fungus Aspergillus flavus.
Some novel complexes of the ligands 1,2-dihydro-1,5-dimethyl-2-phenyl-4-(2- hydroxy-5-methyl phenylazo)-3H-pyrazol-3-one (CAAPH) and 1,2-dihydro-1,5- dimethy1-2-phenyl-4-(2-hydroxy-5-chlorophenylazo)-3H-pyrazol-3-one (CPAAPH) with Cu(II) having the formulae [Cu(LH)Cl2], [CuLH(Ac)2], [CuLH(NO3)2], [CuLH(SO4)], [CuLH(ClO 4)2], [CuLH(NCS)Cl] and [Cu(L′ H)Cl2], [CuL′ H (Ac)2], [CuL′ - (NO3)2], [CuL′ H (SO4)], [CuL′ H (ClO4J2], [CuL′ H(NCS)Cl] (LH=CAAPH and L′ H=CPAAPH) have been synthesized and characterized by elemental analysis, IR, electronic, ESR, NMR, magnetic, conductance measurements and cyclic voltammetric studies. The ligands are found to behave in a neutral bidentate manner. All the complexes are non-electrolytes and square planar with magnetic moment ranging from 1.79 to 1.88 B.M. The X-band ESR spectra of the complexes [Cu(CAAPH)Cl2], [Cu(CAAPH)-(Ac) 2], [Cu(CAAPH)(NO3)2], [Cu(CAAPH)(SO 4)], [Cu(CPAAPH)(ClO4)2] and [Cu(CPAAPH)(NCS)Cl] are seen to be characteristic of Cu(II) in the ligand field with axial symmetry. The complexes [Cu (CAAPH)(SO4)] and [Cu(CPAAPH)Cl2)] are found to be orthorhombic with the unit cell dimensions such as a=5.8564 Å, c=9.4817 Å and c=12.8383 Å; and a=5.3029 Å, b=10.2028 Å and c=11.6127 Å, respectively. The cyclic voltammograms of [Cu(CAAPH)Cl2] and [Cu(CPAAPH)(ClO 4)2] show quasi-reversible peaks which indicates that metal-ligand linkage is more covalent in nature.
ESR spectra of copper complexes have been interpreted by means of molecular orbital theory, and the ``covalent'' character of both σ and π bonds have been discussed for a variety of compounds. Overlap integrals have been considered in a consistent manner in treating σ bonds. Particular attention has been given to Cu phthalocyanine and several of its derivatives. The in‐plane π bonding may be as important in determining the properties of a Cu complex as is the in‐plane σ bonding.
Ternary complexes of Cu(II) with acetylacetone and various salicylic acids (viz., salicylic, 5-chloro-, 3,5-dibromo-, 3,5-dinitro-, thio-, and acetyl-salicylic acids) were synthesised in pure state and these complexes were characterised by elemental analysis, conductivity, IR data and optical absorption. The antibacterial and antifungal activity studies on these complexes revealed that the ternary complexes are better toxic agents than the binary complexes against certain bacteria and fungi studied. The lipo-philic tendency of these complexes was also studied. Ascorbic acid markedly decreases the antimicrobial activity of the ternary complexes while traces of cobalt completely suppresses their toxic action in many cases. Based on these results probable mechanisms for the antimicrobial activity of these complexes are discussed.
A novel tetradentate nitrogen donor [N4] macrocyclic ligand, i.e. 1,3,4,8,9,11-hexaaza-2,5,10,12-tetraoxo-7,14-diphenyl-cyclotetradecane (L), has been synthesized. Mn(II), Co(II), Ni(II)
and Cu(II) complexes of this ligand have been prepared and subjected to elemental analyses, molar conductance measurements,
magnetic susceptibility measurements, mass, 1H-n.m.r. (Ligand), i.r., electronic, and e.p.r. spectral studies. On the basis of molar conductance the Mn(II), Co(II) and
Cu(II) complexes may be formulated as [M(L)X2] [where X = Cl− & NO
3
−
] due to their non-electrolytic nature in dimethylformamide (DMF). Whereas the Ni(II) complexes are 1:2 electrolytes and formulated
as [Ni(L)]X2. All the complexes are of the high spin type and are six/four coordinate. On the basis of i.r., electronic and e.p.r. spectral
studies an octahedral geometry has been assigned to Mn(II) and Co(II), square planar for Ni(II) complexes, and tetragonal
for Cu(II) complexes. The antimicrobial activities of the ligand and its complexes, as growth inhibiting agents, have been
screened in vitro against several species of bacteria and plant pathogenic fungi.