DIVALENT METAL COMPLEX OF COUMARIN: SYNTHESIS & CYTOTOXIC EVALUATION
HTML Full TextDIVALENT METAL COMPLEX OF COUMARIN: SYNTHESIS & CYTOTOXIC EVALUATION
Akshata S. Menasinakai, Pradeep Kumar M. Ronad * and Pratibha M. Huded
Department of Pharmaceutical Chemistry, KLE College of Pharmacy, Vidyanagar, Hubballi, Karnataka, India.
ABSTRACT: Introduction: Coumarins are secondary metabolites widely spread in nature. Due to their broad pharmacological activities, many natural and synthetic coumarins and more complex related derivatives are of interest. The coumarin is extremely variable in structure due to the various types of substitutions in their basic structure, influencing their biological activity. Metal complexes of coumarins obtained revealed higher biological activity than their ligand. Metal complexes play a vital role as chemotherapeutic agents. Methods: 7-amino-4-methylcoumarin refluxed with substituted aromatic aldehydes in absolute alcohol in presence of acetic anhydride and was washed with cold water to give Schiff bases of 7-amino-4-methylcoumarin (4a-4j). Further, the metal complexes of coumarin Schiff base (5a-5j) were synthesized by dissolving both Schiff base of 7-amino-4-methylcoumarin and metal sulphates in methanol and are stirred at 250C with dropwise addition of a dil. ammonia. Result and Conclusion: Screening the copper metal complexes against breast cancer cell line (MDA MB 231) with standard Paclitaxel using MTT assay method. The synthesized metal complexes show anticancer activity in a concentration-dependent manner. The IC50 values of metal complexes were found as 258.3, 256.2, 241.3, 262.1, 178.10, 257.8, 175.2, 272.1, 178.3 and 280.6 µg/ml respectively, when compared to standard Paclitaxel IC50 257 µg/ml under experimental conditions. The primary in-vitro anticancer activity results revealed that 5a, 5b, 5c and 5d showed good anticancer activity.
Keywords: Coumarins, Schiff Base, Pechmann reaction, Anticancer activity
INTRODUCTION: Cancers or tumors are groups of cells that have undergone unregulated growth and will often form a mass or lump that may distribute diffusely 1. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity, and excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation and environmental pollutants.
In the developing world, 15% of cancers are due to Helicobacter pylori, hepatitis B, hepatitis C, human papillomavirus infection, Epstein-Barr virus, and human immunodeficiency virus. Approximately 5-10% of cancers are due to inherited genetic defects from a person’s parents 2.
Coumarins are secondary metabolites widely spread in nature and found in green plants, fungi, bacteria, in some animal species. Many natural and synthetic coumarins and more complex related derivatives are of interest due to its broad pharmacological activities, including anti-bacterial 3, 4, anti microbial 5, anti-thrombotic, vasodilator scavenging of reactive oxygen species and anti-tumorigenic, appears to be based on coumarin nucleus. The coumarin is extremely variable in structure, due to the various types of substitutions in their basic structure, influencing their biological activity 6, 7. Coumarin (2-H-1-benzopyran-2-one) originates from a wide variety of plants, animals, bacteria, and fungi and contains a class of the phenolic group composed of fused benzene and α-pyrone ring. As we know, coumarin's pharmacological action depends on the nature of the group present and its substitution pattern on the basic nucleus. Some reports have shown that substitution at the C-4 position of coumarin exhibits tremendous cytotoxic activity 8-11 in various cancer cell lines. Coumarins have been investigated for the complexing ability with metals.
Metal complexes of coumarins obtained revealed higher biological activity than their ligand 12. Metal complexes of O, S, and N containing Schiff bases have been the subject of current growing interest because it has a wide range of pharmacological activities1 13-15. Metal complexes play a vital role as chemotherapeutic agents1 16-29. Earlier platinum complex cisplatin was most commonly used as an effective drug. Because of its limited use and resistance, research is been diverted to other metals which show better activity; they started using physiological metals. One of them is copper 30-33, which plays a major role in the human system. Another most important reason to use copper metal is the perspective of adopting cytotoxic mechanism and has a great variety of complexing abilities 34.
MATERIALS AND METHODS: The title compounds were synthesized as per scheme I. m-aminophenol condensed with ethyl acetate in the presence of ethyl chloroformate to give 3-hydroxyphenylurethane (1). This condensation with the ethyl acetoacetate in 75% sulphuric acid gives rise to 7-carbethoxyamino-4-methylcoumarin (2). This on refluxing with the mixture of sulphuric acid and glacial acetic acid followed by diluting with water and next made alkaline with the mixture of sodium hydroxide and sodium carbonate to form 7-amino-4-methylcoumarin (3). This product was further refluxed with substituted aromatic aldehydes in absolute alcohol in the presence of acetic anhydride and was washed with cold water to give Schiff bases of 7-amino-4-methyl coumarin (4a-4j). Further, the metal complexes of coumarin Schiff base (5a-5j) were synthesized by dissolving both Schiff base of 7-amino-4-methyl coumarin and metal sulphates in methanol and are added dropwise and stirred at 25°C with the dropwise addition of a dilute solution of ammonia 35.
TABLE 1: STRUCTURE AND CHEMICAL NAME OF SCHIFF BASES OF 7-AMINO-4-METHYL COUMARIN
TABLE 2: STRUCTURE AND CHEMICAL NAME OF A COPPER COMPLEX OF SCHIFF BASES OF 7-AMINO-4-METHYL COUMARIN
In-vitro Anticancer Activity 36, 37, 38:
Cytotoxicity by MTT Assay: The human carcinoma cell lines were purchased from the national center for cell sciences (NCCS) in Pune. The cell line was cultured in DMEM with low glucose medium (Cat No-11965-092), which was supplemented with 10% heat-inactivated fetal calf serum (FBS) and 1% antibiotic-antimycotic 100X solution and incubated in a CO2 incubator [Eppendorf, New Brunswick, Galaxy 170 R, Germany] maintained at 310K in 5% CO2 and 95% humidity until the completion of the experiment. The cells were seeded at a density of approximately 5×103 cells [well in a 96-well flat-bottomed microplate and maintained at 310K in 95% humidity and 5% CO2 overnight. Then different concentrations [i.e., 31.25, 62.5, 125, 250, and 500 µg/ml] of the complex were added to the wells, which were incubated for another 48 hours. The cells were washed twice with phosphate buffer solution and 20µl of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) staining solution (5mg/ml in phosphate buffer solution) was added to each well, which was then incubated at 310K. After 4 hours, the formazan formed was dissolved in the 100µl of dimethylsulfoxide (DMSO), and the absorbance was recorded at 570 nm using the microplate reader.
The principle of MTT Assay: This is a colorimetric assay that measures the reduction of yellow 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) by mitochondrial succinate dehydrogenase. The MTT enters the cells and passes into the mitochondria, where it is reduced to an insoluble, colored (dark purple) formazan product. The cells are then solubilized with an organic solvent (e.g., DMSO, isopropanol), and the released; solubilized formazan reagent is measured spectrophotometrically. Since, the reduction of MTT can only occur in metabolically active cells, the level of activity is a measure of the viability of the cells.
Synthetic Studies 35:
RESULTS AND DISCUSSION:
Synthesis: Title compounds were synthesized as shown in Scheme I. The physical data of the synthesized.
Schiff bases of 7-amino-4-methylcoumarins are given in Table 3, and the Copper metal complexes of those are given in Table 4.
TABLE 3: PHYSICAL DATA OF N-SUBSTITUTED SCHIFF BASES OF 7-AMINO-4-METHYL COUMARIN
Compound* | R | Colour | % yield | Melting Point (oC) | Rf value# | Molecular Formula |
4a | o,m-C2H6O2-C7H4 | Yellow | 87.3% | 178-179 | 0.62 | C19H17O4N |
4b | p-N(CH3)2C7H5 | Yellow | 71.69% | >300 | 0..78 | C19H18O2N2 |
4c | o,m-Cl2-C7H4 | Light brown | 63.98% | 150-152 | 0.51 | C17H11O2NCl2 |
4d | m-OH-C7H5 | Light brown | 82% | 184-186 | 0.74 | C17H13O3N |
4e | m-NO2-C7H5 | Yellow | 73.4% | 192-194 | 0.43 | C17H12O4N2 |
4f | o,m,p-C3H9O3-C7H3 | Pale red | 71.35% | >300 | 0.69 | C20H19O5N |
4g | m-Cl-C7H5 | Pale brown | 78% | 217-218 | 0.75 | C17H12O2NCl |
4h | o-OH-C7H5 | Pale brown | 74.18% | 162-164 | 0.81 | C17H13O3N |
4i | m-Br-C7H5 | Yellow | 70% | 154-156 | 0.6 | C17H12O2NBr |
4j | p-CH3-C7H5 | Yellow | 80% | >300 | 0.72 | C18H15O2N |
TABLE 4: PHYSICAL DATA OF COPPER METAL COMPLEXES OF N-SUBSTITUTED SCHIFF BASES OF 7-AMINO-4-METHYL COUMARIN
Compound* | R | Colour | % yield | Melting Point (oC) | Molecular Formula |
5a | o,m-C2H6O2-C7H4 | Mint Green | 82.3% | 265-268 | C38H34O8N2Cu |
5b | p-N(CH3)2C7H5 | Blue | 75.19% | 250-252 | C38H36O4N4Cu |
5c | o,m-Cl2-C7H4 | Violet | 60.55% | 281-282 | C34H22O4N2Cl4Cu |
5d | m-OH-C7H5 | Blue | 60.9% | 234-236 | C34H26O6N2Cu |
5e | m-NO2-C7H5 | Mint Green | 65% | 244-246 | C34H24O8N4Cu |
5f | o,m,p-C3H9O3-C7H3 | Blue | 68.35% | 280-285 | C40H38O10N2Cu |
5g | m-Cl-C7H5 | Purple | 68.18% | 257-258 | C34H24O4N2Cl2Cu |
5h | o-OH-C7H5 | Blue | 66.50% | 283-285 | C34H26O6N2Cu |
5i | m-Br-C7H5 | Blue | 70.20% | 276-278 | C34H24O4N2Br2Cu |
5j | p-CH3-C7H5 | Blue | 80% | 280-282 | C36H30O4N2Cu |
TABLE 5: CELL VIABILITY (MDA MB 231) OF COPPER METAL COMPLEXES OF N-SUBSTITUTED SCHIFF BASES OF 7-AMINO-4-METHYL COUMARIN BY MTT ASSAY
Compound* | R | Concentration (µg/ml) | |||||
0 | 31.25 | 62.5 | 125 | 250 | 500 | ||
5a | o,m-C2H6O2-C7H4 | - | 95.12 | 81.20 | 72.25 | 60.78 | 55.00 |
5b | p-N(CH3)2C7H5 | - | 95.03 | 72.01 | 70.19 | 72.80 | 48.44 |
5c | o,m-Cl2-C7H4 | - | 92.20 | 75.60 | 72.25 | 60.12 | 48.00 |
5d | m-OH-C7H5 | - | 82.32 | 80.29 | 75.32 | 69.91 | 54.55 |
5e | m-NO2-C7H5 | - | 94.24 | 77.44 | 68.41 | 60.14 | 90.12 |
5f | o,m,p-C3H9O3-C7H3 | - | 95.52 | 82.25 | 76.83 | 65.15 | 57.98 |
5g | m-Cl-C7H5 | - | 83.48 | 70.31 | 73.25 | 63.12 | 60.03 |
5h | o-OH-C7H5 | - | 95.13 | 82.23 | 78.56 | 72.88 | 51.53 |
5i | m-Br-C7H5 | - | 97.50 | 76.88 | 72.02 | 80.83 | 54.38 |
5j | p-CH3-C7H5 | - | 96.50 | 86.59 | 80.22 | 75.17 | 76.25 |
Standard drug (Paclitaxel) | - | 98.56 | 81.94 | 65.73 | 56.17 | 49.23 | |
Control | 100 | - | - | - | - | - |
Standard drug - Paclitaxel - 0.3µM or 257µg/ml
Surviving cells (%) = Mean OD of test compound / Mean OD of Nagative control × 100
Inhibiting cells (%) = 100-surviving cells DMSO concentration is less than 1.5% in Experiments Table 5 discloses the cell viability % of a copper metal complex of N substituted Schiff base 7-amino-4-methylcoumarin with the standard paclitaxel against MDA-MB231.
TABLE 6: IC50 VALUES (MDA MB 231) OF COPPER METAL COMPLEXES OF N-SUBSTITUTED SCHIFF BASES OF 7-AMINO-4-METHYL COUMARIN
Compound* | R | IC50 value in µg/ml |
5a | o,m-C2H6O2-C7H4 | 258.3 |
5b | p-N(CH3)2C7H5 | 256.2 |
5c | o,m-Cl2-C7H4 | 241.3 |
5d | m-OH-C7H5 | 262.1 |
5e | m-NO2-C7H5 | 178.10 |
5f | o,m,p-C3H9O3-C7H3 | 257.8 |
5g | m-Cl-C7H5 | 175.2 |
5h | o-OH-C7H5 | 272.1 |
5i | m-Br-C7H5 | 178.3 |
5j | p-CH3-C7H5 | 280.6 |
Table 6 discloses the IC50 value of copper metal complex of N substituted Schiff base 7-amino-4-methylcoumarin with the standard paclitaxel against MDA-MB231. The anticancer activity screening of the copper metal complexes against breast cancer cell line (MDA MB 231) with standard Paclitaxel by using MTT assay method. The higher toxicity of the synthesized compounds than standard Paclitaxel induces death.
The synthesized metal complexes show anticancer activity in a concentration-dependent manner. The IC50 values o metal complexes, which are screened against MDA MB 231 breast cancer cell line, were found as 258.3, 256.2, 241.3, 262.1, 178.10, 257.8, 175.2, 272.1, 178.3 and 280.6, respectively, when compared to standard Paclitaxel IC50 257 µg/ml under experimental conditions.
Among the synthesized compounds, 5a shows %cell viability of 95.12, 81.20, 72.25, 60.78 and 55 at concentration 31.5, 62.5, 125, 250 and 500 µg/ml respectively. Compound 5b shows 95.03, 72.01, 70.19, 72.80 and 48.44 at concentration 31.5, 62.5, 125 and 500 respectively.
Compond 5c 92.20, 75.60, 72.25, 60.12 and 48 at concentrations 31.5, 62.5, 125, 250 and 500 µg/ml respectively. Compound 5d shows 82.32, 80.29, 75.32, 69.91 and 54.5 at com-centrations 31.5, 62.5, 125, 250 and 500 µg/ml respectively. Standard Paclitaxel showed 98.56, 81.94 and 65.73, 56.17 and 49.23 at concentrations 31.5, 62.5, 125, , 250 and 500 µg/ml respectively. All the above compounds showed good anticancer activity.
CONCLUSION: The primary in-vitro anticancer activity results revealed that compouds of copper complex of 7-(2,5-dimethoxybenazylideneamino)-4-methyl-2H-chromen-2-one(5a), copper complex of 7 - (4 - dimethylaminobenazylideneamino) - 4-methyl - 2H – chromen – 2 - one(5b), 7-(2,3-dichlorobenazylideneamino)-4-methyl-2H-chromen -2-one(5c) and 7-(3-hydroxybenazylideneamino)-4-methyl-2H-chromen-2-one(5d) showed good anticancer activity.
The main objective of our synthesized compounds is to have better anticancer activity with lesser side effects, but we partially succeeded, as all the synthesized compounds other than 5a, 5b, 5c and 5d did not show a good anticancer activity. The compounds 5a, 5b, 5c and 5d showed good activity compared to standard. The possible improvements in the anticancer activity can be achieved by slight modifications in the ring substituents and /or extensive additional fractionation warrants further investigation. Further investigation is necessary for this field in search of potent anticancer activity.
ACKNOWLEDGMENT: Authors express their heartfelt gratitude to KLES College of Pharmacy, Vidyanagar, Hubballi, for their constant support encouragement. Authors sincerely thank Kishore Bhatt sir for in-vitro anti-mycobacterial activity characterization. The authors are also grateful to Mr. Prem for their assistance in the IR experiments.
CONFLICT OF INTEREST: Authors hereby declare no financial/commercial conflicts of interest.
REFERENCES:
- Mitchell B: Introduction to Cancer Chemotherapeutics. 2009; 109(7): 2007–9.
- Global, regional and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980 – 2015 : a systematic analysis for the Global Burden of Disease Study 2015. 2016; 1980–2015.
- Jopp M, Becker J, Becker S, Miska A, Gandin V and Marzano C: Anticancer activity of a series of copper(II) complexes with tripodal ligands. Eur J Med Chem Elsevier Masson SAS; 2017; 132(Ii): 274–81.
- Ashok D, Gundu S, Aamate VK, Devulapally MG, Bathini R, Manga V. AC SC. J Mol Struct [Internet]. Elsevier B.V.; 2017; (2018). Available from: https://doi.org/10.1016/j.molstruc.2017.12.080
- Lukasz Balewski, SylwiaSzulta, Aleksandra Jalińska and Anita Kornika. A Mini-Review: Recent Advances in Coumarin-Metal Complexes with Biological Properties. Frontiers in Chemistry 2021. https://doi.org/10.3389/fchem.2021.781779
- Pivetta T, Valletta E, Ferino G, Isaia F, Pani A and Vascellari S: Novel coumarins and related copper complexes with biological activity: DNA binding, molecular docking and in-vitro antiproliferative activity. J InorgBiochem. Elsevier Inc 2017; 177: 101–9.
- Liu L, Hu Y, Shen YF, Wang GX and Zhu B: Evaluation on antiviral activity of coumarin derivatives against spring viraemia of carp virus in epithelioma Papulosum cyprini Antiviral Res [Internet]. Elsevier Ltd; 2017; 144: 173–85.
- Kraljević TG, Harej A, Sedić M, Pavelić SK, Stepanić V epitheliomapapulosumcyprini Drenjančević D: Synthesis, in-vitro anticancer and antibacterial activities and in silico studies of new 4-substituted 1,2,3-triazole–coumarin hybrids. Eur J Med Chem [Internet]. Elsevier Ltd 2016; 124: 794–808.
- Singh H, Singh JV, Gupta MK, Saxena AK, Sharma S epitheliomapapulosumcyprini Nepali K: Triazole tethered isatin-coumarin based molecular hybrids as novel antitubulin agents: Design, synthesis, biological investigation and docking studies. Bioorganic Med Chem Lett [Internet] 2017; 27(17): 3974–9.
- Dandriyal J, Singla R, Kumar M epitheliomapapulosumcyprini Jaitak V: Recent developments of C-4 substituted coumarin derivatives as anticancer agents. Eur J Med Chem Elsevier Ltd 2016; 119: 141–68.
- Edward N, Saidu B, Valente S, Bana E, Kirsch G and Bagrel D: Bioorganic & Medicinal Chemistry Coumarin polysulfides inhibit cell growth and induce apoptosis in HCT116 colon cancer cells. Bioorg Med Chem [Internet]. Elsevier Ltd 2012; 20(4): 1584–93.
- Zhu T, Chen R, Yu HAO, Feng YAN, Chen J and Lu QIN: Antitumor effect of a copper (II) complex of a coumarin derivative and phenanthroline on lung adenocarcinoma cells and the mechanism of action. Molecular Medicine Reporters 2014; (Ii): 2477–82.
- Enyedy A, Creaven BS, Czegl E, Devereux M, Kia AF and Karcz D: Biological activity and coordination modes of copper(II) complexes of Schiff base-derived coumarin ligands. Royal Society of Cemistry 2010; 39: 10854–65.
- Patil SA, Unki SN, Kulkarni AD, Naik VH, Badami PS. Spectrochimica Acta Part A : Molecular and Biomolecular Spectroscopy Co (II), Ni (II) and Cu(II) complexes with coumarin-8-yl Schiff-bases : Spectroscopic, in-vitro antimicrobial, DNA cleavage and fluorescence studies. Spectrochim Acta Part A Mol Biomol Spectrosc [Internet]. Elsevier BV 2011; 79(5): 1128–36.
- Linert W: Synthesis, spectroscopic studies and inhibitory activity against bactria and fungi of acyclic and macrocyclic transition metal complexes containing a triamine coumarine schiff base ligand. Spectrochim ACTA PART A Mol Biomol Spectrosc [Internet]. Elsevier B V 2015.
- Jopp M, Becker J, Becker S, Miska A, Gandin V and Marzano C: Anticancer activity of a series of copper(II) complexes with tripodal ligands. Eur J Med Chem Elsevier Masson SAS 2017; 132(Ii): 274–81.
- Acilan C, Cevatemre B, Adiguzel Z, Karakas D, Ulukaya E and Ribeiro N: Synthesis, biological characterization and evaluation of molecular mechanisms of novel copper complexes as anticancer agents. Biochim Biophys Acta - Gen Subj. Elsevier BV 2017; 1861(2): 218–34.
- Ostrowska K, Maciejewska D, Drzewiecka-Antonik A, Klepka MT, Wolska A and Dobrzycki Ł: Synthesis, spectroscopic characterization, X-ray study and in-vitro cytotoxicity of 5-hydroxycoumarin derivatives and their copper complexes. J Mol Struct Elsevier BV 2017; 1145: 292–9.
- Solairaj D, Rameshthangam P and Arunachalam G: Anticancer activity of silver and copper embedded chitin nanocomposites against human breast cancer (MCF-7) cells. Int J Biol Macromol. Elsevier BV 2017; 105: 608–19.
- Suwalsky M, Castillo I, Sánchez-eguía BN, José M, Dukes N and Santiago-osorio E: In-vitro effacts of benzimidazole / thioether-copper complexes with antitumor activity on human erythrocytes. J Inorg Biochem Elsevier 2018; 178; 2017): 87–93.
- Moghadam ME, Divsalar A, Zare MS, Gholizadeh R, Mahalleh D and Saghatforosh L: Anticancer, the antibacterial and antifungal activity of new ni (ii) and cu(ii) complexes of imidazole- phenanthroline derivatives. Taylor & Francis 2017; 36: 667-675.
- Sathisha MP, Shetti UN, Revankar VK, Pai KSR. Synthesis and antitumor studies on novel Co (II), Ni (II) and Cu (II) metal complexes of bis (3-acetylcoumarin) thiocarbohydrazone. Eur J Med Chem [Internet]. Elsevier Masson SAS 2008; 43(11): 2338–46.
- El-Bindary AA, N Hassan and MA: El-Afify:Synthesis and structural characterization of some divalent metal complexes: DNA binding and antitumor activity. Journal of Molecular Liquids 2017; 242: 213-228.
- Thirunavukkarasu T, Sparkes HA, Natarajan K and Gnanasoundari VG: Synthesis, characterization and biological studies of a novel Cu(II) Schiff base complex. Inorganica Chimica Acta 24 March 2018; 473: 255-262.
- Klepka MT, Drzewiecka-Antonik A, Wolska A, Rejmak P, Ostrowska K and Hejchman E: Synthesis, structural studies and biological activity of new Cu(II) complexes with acetyl derivatives of 7-hydroxy-4-methylcoumarin. J Inorg Biochem 2015; 145: 94–100.
- Hamulakova S, Poprac P, Jomova K, Brezova V, Lauro P and Drostinova L: Targeting copper(II)-induced oxidative stress and the acetylcholinesterase system in Alzheimer’s disease using multifunctional tacrine-coumarin hybrid molecules. J InorgBiochem [Internet]. Elsevier BV 2016; 161(Ii): 52–62.
- Sanz del Olmo N, Maroto-Díaz M, Gómez R, Ortega P, Cangiotti M and Ottaviani MF: Carbosilane metallodendrimers based on copper (II) complexes: Synthesis, EPR characterization and anticancer activity. J Inorg Biochem [Internet]. Elsevier Inc 2017; 177(Ii): 211–8.
- Gaál A, Mihucz VG, Bősze S, Szabó I, Baranyi M and Horváth P: Comparative in-vitro investigation of anticancer copper chelating agents. Microchem J [Internet]. Elsevier BV 2018; 136: 227–35.
- Zhang Y, Zhang Z, Gou Y, Jiang M, Khan H and Zhou Z: Design an anticancer copper(II) pro-drug based on the flexible IIA subdomain of human serum albumin. J InorgBiochem. Elsevier 2017; 172(November 2016): 1–8.
- Ottaviani MF, Yordanova S, Cangiotti M, Vasileva-Tonkova E, Coppola C and Stoyanov S: Spectral characterization and in-vitro microbiological activity of new bis-1,8-naphthalimides and their Cu(II) complexes. J Mol Struct. Elsevier Ltd 2016; 1110(Ii): 72–82.
- Gudasi KB, Patil MS and Vadavi RS: Synthesis, characterization of copper (II), cobalt (II), nickel (II), zinc (II) and cadmium (II) complexes of [7-hydroxy-4-methyl-8- coumarinyl] glycine and a comparative study of their microbial activities. Eur J Med Chem. Elsevier Masson SAS 2008; 43(11): 2436–41. Available from: http://dx.doi.org/10.1016/j.ejmech.2008.01.028
- Arif R, Sirajuddin P, Ansari IA, Shahid M, Irfan M and Alam S: Synthesis , molecular docking and DNA binding studies of phthalimide-based copper ( II ) complex : In vitro antibacterial , hemolytic and antioxidant assessment. J Mol Struct [Internet]. Elsevier B.V 2018; 1160: 142–53.
- Kumar G, Kumar D, Devi S, Johari R and Singh CP: European Journal of Medicinal Chemistry Synthesis, spectral characterization and antimicrobial evaluation of Schiff base Cu ( II ), Ni (II) and Co (II) complexes. Eur J Med Chem[Internet]. Elsevier Masson SAS; 2010; 45(7): 3056–62.
- Prosser KE, Chang SW, Saraci F, Le PH and Walsby CJ: Anticancer copper pyridine benzimidazole complexes: ROS generation, biomolecule interactions, and cytotoxicity. J Inorg Biochem. Elsevier BV 2017; 167: 89–99.
- Ronad PM, Hunashal RD, Darbhamalla S, Maddi VS. Synthesis and Evaluation of Anti- inflammatory and Analgesic Activities of a Novel Series of Substituted-N- benzamides. Arzneimittel Forschung 2008; 58(12): 641–6.
- Rayaji A and Swamy AHMV: Synthesis and Evaluation of Anti-Inflammatory and Analgesic activities of some Newly Synthesized metal complexs of Coumarin Schiff bases. Indian Drugs 2016; 53; 2015.
- Shah T, Joshi K, Mishra S, Otiv S and Kumbar V: Molecular and cellular effects of vitamin B12 forms on human trophoblast cells in presence of excessive folate. Biomed Pharmacother[Internet] 2016; 84: 526–34.
- Rawat A and Reddy VB: Recent Advances on anticancer activity of coumarin derivatives. European Journal of Medicinal Chemistry Reports August 2022; 5: 100038.
How to cite this article:
Menasinakai AS, Ronad PM and Huded PM: Divalent metal complex of coumarin: synthesis & cytotoxic evaluation. Int J Pharm Sci & Res 2022; 13(12): 4918-27. doi: 10.13040/IJPSR.0975-8232.13(12).4918-27.
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Akshata S. Menasinakai, Pradeep Kumar M. Ronad * and Pratibha M. Huded
Department of Pharmaceutical Chemistry, KLE College of Pharmacy, Vidyanagar, Hubballi, Karnataka, India.
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01 April 2022
04 May 2022
27 May 2022
10.13040/IJPSR.0975-8232.13 (12). 4918-27
01 December 2022