In-vitro Anticancer Activity of Copper (II) and Zinc (II) Complexes with Derived Schiff Base Ligands

Based on World Health Organization (WHO) report, it was estimated that one in five people before age 75 will suffer from cancer during their lifetime, and more than 13 million cancers death will happen in 2030. Chemotherapy is a basic approach for the treatment of cancer diseases. However, because of drug resistance and considerable side effects drug-induced toxicity, the discovery of new metal analogs with promising activity and high therapeutic index is an urgent need. The fundamental role of copper and the recognition of its complexes as important bioactive compounds in vitro and in vivo aroused an ever-increasing interest in these agents as potential drugs for therapeutic intervention in various diseases. Schiff bases are a critical class of compounds in medical chemistry that have demonstrated significant chemotherapeutic and antibacterial application. Schiff base Cu(II) complexes revealed great potential for antiproliferative, antibacterial, and gastroprotective activity. Coumarins are a wide class of natural and synthetic compounds that showed diverse pharmacological activities including anticancer activity. Among the wide variety of coumarins, 7-hydroxycoumarin derivatives have been shown to possess desirable antiproliferative activities. In particular, their antibacterial, antifungal and anticancer activities make the compounds attractive for further derivatization and screening as novel therapeutic agents. Taking these compounds as lead, we have designed and synthesized a series of new copper(II) complexes with coumarin-derived Schiff base ligands. Two series of Schiff bases were prepared by condensation of 8-formyl-7-hydroxy-4-methylcoumarin and 8-acetyl-7-hydroxy-4-methylcoumarin with p-substituted aniline derivatives. These compounds were used as ligands in the synthesis of copper(II) complexes. The obtained Schiff bases as well as copper complexes are mostly novel molecules. Only the products of condensation 8-formyl-7-hydroxy-4-methylcoumarin with p-toluidine and 8-acetyl-7-hydroxy-4-methylcoumarin with p-toluidine and its copper(II) complex were synthesized, but the anticancer activity of these compounds was not determined. The assay of their cytotoxic activity is in progress. Preliminary, we have identified two copper(II) coordination compounds of 7-hydroxy-8-[1-(4-methoxyphenyl imino)ethyl]-4-methyl-2H-chromen-2-one and 7-hydroxy-8-[1-(4-hydroxyphenyloimino)ethyl]-4-methyl-2H- chromen-2-one having dose-dependent antiproliferative activity on HeLa cancer cell line. Additionally, the Schiff bases – derivatives of substituted salicylaldehydes and 2-hydroxyacetophenones condensed with appropriate anilines were prepared. Such compounds have been reported in scientific papers, their copper complexes have not been assayed yet, and may serve as an useful tool in QSAR investigation.

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Copper(II) complexes of Schiff base ligands as promising anticancer agents

10.7287/peerj.preprints.1830 ◽

2016 ◽

Author(s):

Elżbieta Hejchman ◽

Barbara Sowirka ◽

Magdalena Tomczyk ◽

Dorota Maciejewska

Keyword(s):

Schiff Base ◽

Anticancer Activity ◽

Schiff Bases ◽

Anticancer Agents ◽

Copper Complexes ◽

World Health ◽

Anticancer Activities ◽

Schiff Base Ligands ◽

Drug Induced

Based on World Health Organization (WHO) report, it was estimated that one in five people before age 75 will suffer from cancer during their lifetime, and more than 13 million cancers death will happen in 2030. Chemotherapy is a basic approach for the treatment of cancer diseases. However, because of drug resistance and considerable side effects drug-induced toxicity, the discovery of new metal analogs with promising activity and high therapeutic index is an urgent need. The fundamental role of copper and the recognition of its complexes as important bioactive compounds in vitro and in vivo aroused an ever-increasing interest in these agents as potential drugs for therapeutic intervention in various diseases. Schiff bases are a critical class of compounds in medical chemistry that have demonstrated significant chemotherapeutic and antibacterial application. Schiff base Cu(II) complexes revealed great potential for antiproliferative, antibacterial, and gastroprotective activity. Coumarins are a wide class of natural and synthetic compounds that showed diverse pharmacological activities including anticancer activity. Among the wide variety of coumarins, 7-hydroxycoumarin derivatives have been shown to possess desirable antiproliferative activities. In particular, their antibacterial, antifungal and anticancer activities make the compounds attractive for further derivatization and screening as novel therapeutic agents. Taking these compounds as lead, we have designed and synthesized a series of new copper(II) complexes with coumarin-derived Schiff base ligands. Two series of Schiff bases were prepared by condensation of 8-formyl-7-hydroxy-4-methylcoumarin and 8-acetyl-7-hydroxy-4-methylcoumarin with p-substituted aniline derivatives. These compounds were used as ligands in the synthesis of copper(II) complexes. The obtained Schiff bases as well as copper complexes are mostly novel molecules. Only the products of condensation 8-formyl-7-hydroxy-4-methylcoumarin with p-toluidine and 8-acetyl-7-hydroxy-4-methylcoumarin with p-toluidine and its copper(II) complex were synthesized, but the anticancer activity of these compounds was not determined. The assay of their cytotoxic activity is in progress. Preliminary, we have identified two copper(II) coordination compounds of 7-hydroxy-8-[1-(4-methoxyphenyl imino)ethyl]-4-methyl-2H-chromen-2-one and 7-hydroxy-8-[1-(4-hydroxyphenyloimino)ethyl]-4-methyl-2H- chromen-2-one having dose-dependent antiproliferative activity on HeLa cancer cell line. Additionally, the Schiff bases – derivatives of substituted salicylaldehydes and 2-hydroxyacetophenones condensed with appropriate anilines were prepared. Such compounds have been reported in scientific papers, their copper complexes have not been assayed yet, and may serve as an useful tool in QSAR investigation.

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In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

Antibiotics ◽

10.3390/antibiotics10060728 ◽

2021 ◽

Vol 10 (6) ◽

pp. 728

Author(s):

Alberto Aragón-Muriel ◽

Yamil Liscano ◽

Yulieth Upegui ◽

Sara M. Robledo ◽

María Teresa Ramírez-Apan ◽

...

Keyword(s):

Schiff Base ◽

Molecular Docking ◽

Lanthanide Complexes ◽

Human Tumor ◽

Model Membranes ◽

Leishmania Braziliensis ◽

Cytotoxic Activities ◽

Schiff Base Ligands ◽

Major Interest

Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC® 25923, L. monocytogenes ATCC® 19115) and two Gram-negative strains (E. coli ATCC® 25922, P. aeruginosa ATCC® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S.aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study.

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Copper(II) complexes with tridentate halogen‐substituted Schiff base ligands: synthesis, crystal structures and investigating the effect of halogenation, leaving group and ligand flexibility on antiproliferative activities

Dalton Transactions ◽

10.1039/d0dt03962d ◽

2021 ◽

Author(s):

Nazanin Kordestani ◽

Hadi Amiri Rudbari ◽

Alexandra R Fernandes ◽

Luís R Raposo ◽

André Luz ◽

...

Keyword(s):

Schiff Base ◽

Anticancer Activity ◽

Crystal Structures ◽

Copper Complexes ◽

Schiff Base Ligands ◽

Leaving Group ◽

Leaving Groups ◽

Tridentate Schiff Base ◽

Antiproliferative Activities

To investigate the effect of different halogen substituents, leaving groups and the flexibility of ligand on the anticancer activity of copper complexes, sixteen copper(II) complexes with eight different tridentate Schiff-base...

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Synthesis, Characterization, Antimicrobial and Anticancer Activity of New Bidentate Schiff Base Ligand and their Transition Metal(II) Complexes

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23171 ◽

2021 ◽

Vol 33 (7) ◽

pp. 1488-1494

Author(s):

S. Arulmozhi ◽

G. Sasikumar ◽

A. Subramani ◽

A. Sudha ◽

S.J. Askar Ali

Keyword(s):

Schiff Base ◽

Anticancer Activity ◽

Cell Lines ◽

Schiff Base Ligand ◽

Pathogenic Bacteria ◽

Human Tumor ◽

Spectral Studies ◽

Breast Adenocarcinoma ◽

Human Colon Cancer

The metal(II) complexes were synthesized by addition of corresponding MCl2 (M = Mn2+, Ni2+, Cu2+ and Zn2+) with 1,2-bis(1H-pyrrol-2-ylmethylene)diazane in methanol. The ligand acts as a bidentate as confirmed from the mass, IR, UV, NMR and EPR spectral studies. The Schiff base ligand forms hexa-coordinated complexes having octahedral geometry for Mn(II), Ni(II), Zn(II) and Cu(II) complexes. The metal complexes showed an excellent antimicrobial activity spectrum in vitro against both Gram-negative (Klebsiella pneumoniae and Acinetobacter baumannii), Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and human pathogenic bacteria isolates. To find the binding affinity with protein BSA kinase, for that molecular docking studies were also carried for all the four synthesized metal(II) complexes. The anticancer activity of the synthesized metal(II) complexes was also screened against the three human tumor cell lines MCF7 human breast adenocarcinoma cell line, CaSki human caucasian cervical epidermoid carcinoma and HCT116 human colon cancer cell lines. The present study showed that Zn(II) complex showed potent inhibition by the ratio of 80% as compared to the inhibition in the normal cells (L-6).

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Synthesis , Spectroscopic and Antibacterial Studies of Zinc(II) Complexes Derived from Salicylaldehyde, Leucylalanine and Glycylglycine

Baghdad Science Journal ◽

10.21123/bsj.9.3.532-540 ◽

2012 ◽

Vol 9 (3) ◽

pp. 532-540 ◽

Cited By ~ 5

Author(s):

Baghdad Science Journal

Keyword(s):

Schiff Base ◽

Bacterial Species ◽

Conductivity Measurement ◽

Growth Inhibitor ◽

Molar Conductance ◽

Diffusion Method ◽

Schiff Base Ligands ◽

Elemental Analyses ◽

L1 And L2

Two Schiff base ligands L1 and L2 have been obtained by condensation of salicylaldehyde respectively with leucylalanine and glycylglycine then their complexes with Zn(II)were prepared and characterized by elemental analyses , conductivity measurement , IR and UV-Vis .The molar conductance measurement indicated that the Zn(II) complexes are 1:1 non-electrolytes. The IR data demonstrated that the tetradentate binding of the ligands L1 and L2 . The in vitro biological screening effect of the investigated compounds have been tested against the bacterial species Staphlococcus aureus, Escherichia coil , Klebsiella pneumaniae, Proteus vulgaris and Pseudomonas aeruginosa by the disc diffusion method . A comparative study of inhibition values of the Schiff base ligands and their complexes indicated that the complexes exhibit higher antimicrobial activity than the free ligands . Zinc ions are proven 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 .

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SYNTHESIS, SPECTRAL CHARACTERIZATION AND ANTICANCER EVALUATION OF NEW DIAZENYL SCHIFF BASE DERIVATIVES

INDIAN DRUGS ◽

10.53879/id.54.02.10877 ◽

2017 ◽

Vol 54 (02) ◽

pp. 20-28

Author(s):

P. K. N. Sarangi ◽

◽

J. Sahoo ◽

S. K Paidesetty ◽

G. P. Mohanta

Keyword(s):

Schiff Base ◽

Anticancer Activity ◽

Cell Line ◽

Leukemia Cell ◽

Cancer Cell Line ◽

Leukemia Cell Line ◽

Primary Amines ◽

Schiff Base Derivatives ◽

Mcf 7

A series of several diazenyl Schiff base derivatives were designed and synthesized through azo coupling of diazotised primary amines with the novel synthesized Schiff base ligand (E)-N-((2-chloroquinolin-3-yl) methylene)-4-phenylthiazol-2-amine. All the synthesized compounds have been analysed by different spectral techniques such as elemental analysis, 1H NMR, FT-IR, UV-Vis and LC-MS for their structural confirmation. The above conjugates have been studied for their solvent effects by treating them with different solvents. The results of in vitro cytotoxic study of the synthesized compounds against MCF 7 (human breast cancer cell line) and K562 (Chronic Myeloid Leukemia cell line) revealed that some of the compounds show cytotoxic effect. However, the compounds (NZ)-N-(((4-bromo-3-methylphenyl) diazenyl) (2-chloroquinolin-3-yl) methylene)-4-phenylthiazol-2-amine: (5d) and 4-(((Z)-(2-chloroquinolin-3- yl)(4-phenylthiazol-2-ylimino)methyl)diazenyl)phenol (5e) showed potent cytotoxic activity in comparison to other compounds against MCF 7. Corroborating the results of anticancer activity, it is found to be observed that the compound 4- (((Z)- (2-chloroquinolin-3-yl) (4-phenylthiazol-2-ylimino)methyl) diazenyl) phenol (5e) showed excellent anticancer activity against MCF 7, which is further justified by the apoptosis study through Annexin V-FITC/PI analysis.

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SYNTHESIS, MOLLUSCICIDALAND ANTIMICROBIAL POTENTIALITIES OF IRON TRIAD MONONUCLEAR METAL COMPLEXES INCORPORATING TRIDENTATE ASYMMETRICAL SCHIFF BASE LIGANDS CONTAINING SOFT SULFUR COORDINATING ATOM

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i2.36481 ◽

2019 ◽

pp. 103-113

Author(s):

AMAL M ALOSAIMI ◽

INES EL MANNOUBI ◽

SAMI A ZABIN

Keyword(s):

Schiff Base ◽

Metal Complexes ◽

Metal Ion ◽

Lethal Dose ◽

Analytical Techniques ◽

Central Metal ◽

Schiff Base Ligands ◽

Molluscicidal Activity

Objective: This work aimed at synthesizing tridentates asymmetrical Schiff base ligands containing sulfur atom and using them for preparing metal complexes with the iron triad metals. The prepared compounds were assayed in vitro for antimicrobial potential and in vivo molluscicidal activity. Methods: The unsymmetrical tridentate Schiff bases (SL1, SL2, and SL3) were prepared using 2-aminothiophenol as primary amine and condensed with 2-carboxybenzaldehyde, 2-hydroxy-1-naphthaldehyde, and 7-formyl-8-hydroxyquinoline. These ligands were used in preparing metal complexes with iron triad metals. The synthesized Schiff base ligands and their corresponding metal complexes were characterized and their proposed structures were confirmed using different physical and spectroscopic analytical techniques. All ligands and their corresponding metal complexes were assayed against different bacterial and fungal strains using the agar disk-diffusion technique. The molluscicidal activity was performed according to the standard reported methods as cited in the literature and by observing the toxicity and lethal dose according to the WHO guidelines. Results: The synthesized ligands behave as tridentate (NOS) ligands and form mononuclear complexes with the general formula [M(SL)2] with an octahedral geometry around the central metal ion. Metal complexes were non-electrolytic in nature. The in vitro antibacterial and antifungal examination results showed weak activity of the ligands, and there was enhanced activity with the complexes. The in vivo molluscicidal activity of the tested compounds showed good activity. Conclusion: The targeted compounds were prepared successfully, characterized, and showed some biological activity but lower than the standard reference drugs.

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para metallation of 3-acetyl-chromen-2-one Schiff bases in tetranuclear palladacycles: focus on their biomolecular interaction and in vitro cytotoxicity

Dalton Transactions ◽

10.1039/c9dt02663k ◽

2019 ◽

Vol 48 (33) ◽

pp. 12496-12511 ◽

Cited By ~ 4

Author(s):

G. Kalaiarasi ◽

S. Dharani ◽

V. M. Lynch ◽

R. Prabhakaran

Keyword(s):

Schiff Base ◽

Schiff Bases ◽

In Vitro Cytotoxicity ◽

Biomolecular Interaction ◽

Schiff Base Ligands

Three tetranuclear (1–3) complexes and a mononuclear (4) palladium(ii) complex were synthesized from 3-acetyl-chromen-2-one Schiff base ligands [H2-3MAC-Rtsc] (where R = H; CH3; C2H5[H2-3MAC-etsc] or C6H5) and potassium tetrachloropalladate.

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