Drug-DNA Interactions by Burak Coban
Synthesis of novel selenotetrazole purine derivatives and their potential chemotherapeutic activities: an investigation focused on DNA interaction, transcription inhibition and cytotoxicity
Medicinal Chemistry Research Vol. 30 Issue 1 Pages 84-97, 2021
The development of novel chemotherapeutic agents is indispensable to improve cancer treatment. On... more The development of novel chemotherapeutic agents is indispensable to improve cancer treatment. One of the conventional approaches toward the synthesis of anticancer agents is the design of a compound whose structure is similar to purines found in DNA. In this study, a series of novel artificial purine nucleosides bearing selenotetrazole pharmacophore, 4a–4h, were synthesized. In order to get preliminary information about their cytotoxic activities, the interaction of compounds with DNA was investigated by UV titration and agarose gel electrophoresis and transcription inhibition studies were performed. The cytotoxic effects of the compounds against B16 melanoma, OV90 ovarian cancer, JM1 lymphoma cell lines, and PHA-induced peripheral blood lymphocytes were also investigated. In cell assay studies, the effects of the compounds on synthesis and mitosis stage of cell cycle were compared by flow cytometry. Although none of the compounds synthesized interacted with DNA and exhibited transcription inhibition, all of them significantly inhibited DNA synthesis phase and showed cytotoxic activity on cancer and proliferating cells.
DNA Interactions and Antiproliferative Activity Studies of Octahedral Nickel Complexes of Two Extended Phenanthrolines
ChemistrySelect Vol. 6 Issue 34 Pages 9012-9023, 2021
Two new imidazophenanthroline derivatives, namely 2-(4bromo-(2,1,3)-benzothiadiazol-7-yl)-1H-imid... more Two new imidazophenanthroline derivatives, namely 2-(4bromo-(2,1,3)-benzothiadiazol-7-yl)-1H-imidazo[4,5-f][1,10] phenanthroline (btdip), 2-(dibenzofuran-3-yl)-1H-imidazo[4,5f][1,10]phenanthroline (dbfip) and their octahedral nickel complexes [Ni(phen)2
(btdip)]2+ (1) and [Ni(phen)2(dbfip)]2+ (2)
have been synthesized and characterized by CHN analysis, ESIMS, NMR and UV-vis spectra. Their DNA binding abilities were spectrophotometrically, hydrodynamically and electrophoretically studied and found that while btdip binds DNA externally, dbfip binds in the grooves and both of their nickel complexes also bind DNA through grooves giving severe DNA damage in the presence of peroxide. The compounds were screened against four different human cancer cell lines using MTT assay method. The results obtained showed that both ligands are active against DLD-1, and further dbfip is found to be more active than positive control drugs against DLD-1 and HepG2 cell lines. The complex 2 has more antiproliferative effect than 1 against MCF-7 and HepG2 cells. On the other hand, complex 2 was found to have more toxic effect on HepG2 cells than the standard drugs cisplatin and ploxal-S.
Syntheses, spectral and chiral properties and DNA interactions of multi-heterocyclic di- and trinuclear boron complexes
New Journal of Chemistry, 2020
Tetrahedrally coordinated multi-heterocyclic boron complexes are stable, but much less investigat... more Tetrahedrally coordinated multi-heterocyclic boron complexes are stable, but much less investigated inorganic ring systems. In the present study, a series of dinuclear (2aI–2cI and 2aII–2cII) and trinuclear (3aI–3cI and 3aII–3cII) boron complexes were synthesized from SalenH2 type symmetrical bulky ligands [HOArCH[double bond, length as m-dash]N–R–N[double bond, length as m-dash]CHArOH; R = (CH2)n, n = 2 (1a), 3 (1b) and 4 (1c)], arylboronic acids (phenylboronic acid and 4-formylphenylboronic acid), and boric acid for the investigation of their spectral, stereogenic and DNA cleavage activities. The Salen-boron complexes have two equivalent chiral B-centers, giving rise to diastereoisomers. The stereogenic properties of these complexes were investigated by nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopies. The stereoisomers were compared with each other for two different architectural types and a total of 12 Salen-boron complexes with seven- to nine-membered [(B–O–B)–(N–R–N)] heterocycles. The combination of NMR and CD spectra of the complexes shows that the boron complexes (2bI and 3bII) and (2bII and 3bI) from the (CH2)3 precursor give only a cis–meso (RS/SR) isomer and only one trans-enantiomer (RR or SS), respectively. The complexes (2cI, 3cI and 3cII) from the (CH2)4 precursor give only one enantiomer (RR or SS), whereas the boron complexes (2aI, 2aII, 3aI and 3aII) from the (CH2)2 precursor and (2cII) from the (CH2)4 precursor form two diastereoisomers as one enantiomer (RR or SS) and one meso (RS/SR). Furthermore, the DNA cleavage activities of the adducts were determined using agarose gel electrophoresis and UV absorption in order to compare the cleavage efficiency of the boron complexes depending on the type of complexes (dinuclear or trinuclear) and the number of members in the heterocyclic frameworks. In this assay, the seven-membered trinuclear boron complex (3bII) showed the highest cleavage efficiency.
Synthesis of novel selenotetrazole purine derivatives and their potential chemotherapeutic activities
Medicinal Chemistry Research, 2021
The development of novel chemotherapeutic agents is indispensable to improve cancer treatment. On... more The development of novel chemotherapeutic agents is indispensable to improve cancer treatment. One of the conventional approaches toward the synthesis of anticancer agents is the design of a compound whose structure is similar to purines found in DNA. In this study, a series of novel artificial purine nucleosides bearing selenotetrazole pharmacophore, 4a–4h, were synthesized. In order to get preliminary information about their cytotoxic activities, the interaction of compounds with DNA was investigated by UV titration and agarose gel electrophoresis and transcription inhibition studies were performed. The cytotoxic effects of the compounds against B16 melanoma, OV90 ovarian cancer, JM1 lymphoma cell lines, and PHA-induced peripheral blood lymphocytes were also investigated. In cell assay studies, the effects of the compounds on synthesis and mitosis stage of cell cycle were compared by flow cytometry. Although none of the compounds synthesized interacted with DNA and exhibited transcription inhibition, all of them significantly inhibited DNA synthesis phase and showed cytotoxic activity on cancer and proliferating cells.
Synthesis, characterization, duplex‐DNA interactions, and anticancer activities of novel octahedral [Ni(phen)2(dppz‐idzo)]2+ and [Co(phen)2(dppz‐idzo)]3+ complexes
Applied Organometallic Chemistry, 2020
Two new octahedral [Ni(phen)2(dppz‐idzo)]2+ and [Co(phen)2(dppz‐idzo)]3+ complexes have been synt... more Two new octahedral [Ni(phen)2(dppz‐idzo)]2+ and [Co(phen)2(dppz‐idzo)]3+ complexes have been synthesized and characterized by CHN analysis, electrospray ionization‐MS, nuclear magnetic resonance, and UV–Vis spectra. The DNA‐binding ability of these complexes was spectrophotometrically, hydrodynamically, and electrophoretically evaluated which indicated that they strongly intercalate into the DNA double helix, and that both induced severe DNA damage in the presence of peroxide. The complexes also showed strong antiproliferative effect against HepG2 and MDA‐MB‐231 cells. By contrast, they were found to be inactive against the MCF‐7 cell line. The ligand itself was found to be inactive against the cells tested.
Synthesis, Characterization, and Antiproliferative Activity Studies of Novel Benzimidazole‐Imidazopyridine Hybrids as DNA Groove Binders
ChemistrySelect, 2020
A novel benzimidazole‐imidazo[1,2‐a]pyridine hybrid; 2‐(imidazo[1,2‐a]pyridine‐8‐yl)benzimidazole... more A novel benzimidazole‐imidazo[1,2‐a]pyridine hybrid; 2‐(imidazo[1,2‐a]pyridine‐8‐yl)benzimidazole and its symmetrical bis‐ derivative 2,2′‐bis‐(imidazo[1,2‐a]pyridine‐8‐yl)‐1H,1H′‐[5,5′]‐bisbenzimidazole were synthesized and characterized. It was found that these two compounds have a strong DNA groove binding and peroxide mediated DNA‐cleavage properties. Furthermore, these molecules were screened against three different human cell lines namely HepG2, DLD‐1 and MDA‐MB‐231, and these compounds were found to have high cytotoxic activities.
The Pharmaceutical and Chemical Journal, 2020
Benzimidazoles and benzothiodiazoles are biologically active heterocyclic compounds. In here, a n... more Benzimidazoles and benzothiodiazoles are biologically active heterocyclic compounds. In here, a new compound 4-(1H-benzimidazol-2-yl)-7-bromo-2,1,3-benzothiodiazole containing both heterocyclic ring systems was prepared. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the new compound was calculated using the Spartan 10 program. The compound binds to DNA with a moderate strength, and the cytotoxic activity studies show that the relative compound has no antiproliferative activity against cancer cell lines.
Synthesis of naphthalimide derivatives with potential anticancer activity, their comparative ds- and G-quadruplex-DNA binding studies and related biological activities
Molecular Biology Reports, 2020
Two new cytotoxic 1,8-naphthalimide derivatives have been synthesized and characterized. Their bi... more Two new cytotoxic 1,8-naphthalimide derivatives have been synthesized and characterized. Their biological activities as cytotoxicity and antimicrobial activities and inhibitory activities against DNA-polymerase were evaluated. The interactions of compounds with double-stranded- and quadruple-DNA have been studied by UV–Vis, fuorescent intercalator displace-ment, competition dialysis, circular dichroism and the fndings were compared with the parent naphthalimide and the other compounds. The results show that both compounds (1 and 2) and the parent compound NI have strong cytotoxic activities against Beas-2B, MCF-7, HepG2 and MDA-MB-231 cancer cell lines, antimicrobial activities against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and inhibitory activities towards Taq-polymerase and transcriptase. These novel cationic compounds 1 and 2 can stabilize G-quadruplexes DNA according to thermal denaturation experiments, they change the 3D structure of the DNA (see details in CD experiments) and they exhibit diferent binding afnities for q-DNA and ds-DNA revealed by spectrophotometric titrations and competitive dialysis studies.
Synthesis, Spectroscopic, Antimicrobial Activity and Computational Studies of Some Homoleptic and Heteroleptic Metal(II) Complexes of 2-Furoic Acid Hydrazone
ChemistrySelect, 2019
Abstract Homoleptic Co(II), Cu(II) and Ni(II) complexes of a hydrazone derived from 3-acetyl-2-hy... more Abstract Homoleptic Co(II), Cu(II) and Ni(II) complexes of a hydrazone derived from 3-acetyl-2-hydroxy-6-methyl-4H-pyran-4-one (dehydroacetic acid) and 2-furoic acid hydrazide, and their heteroleptic analogues with 2,2′-bipyridine were synthesized. The complexes were characterized by spectroscopic methods (ESI-MS, IR and NMR), elemental analysis, magnetic susceptibility and molar conductance measurements. The homoleptic complexes adopted octahedral geometry, while the heteroleptic analogous had four-coordinate tetrahedral (Co and Cu complexes) and square-planar (Ni complex) geometries. The homoleptic complexes were non-electrolytes, while the heteroleptic complexes were 1:1 electrolytes in DMSO. Antimicrobial experiments indicated that [Cu(L)2] and [Cu(L)(bipy)](CH3COO) had the best antibacterial activities, with MIC of 31.2 and 61.5 μg/ml against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212, respectively. Molecular docking determined that [Cu(L)(bipy)]⋅CH3COO had the highest binding energy and hydrogen bonding interactions with one of the active sites of amino acid residue (LEU73). Density functional theory (DFT) calculations of the complexes revealed that [Cu(L)(bipy)]⋅CH3COO possessed low energy gap, suggesting a higher activity and ability to donate electrons to electron-accepting species of biological targets.
The comparative study of the DNA binding and biological activities of the quaternized dicnq as a dicationic form and its platinum(II) heteroleptic cationic complex
Bioorganic Chemistry, 2019
The square-planar heteroleptic Pt(II) coordination compound [Pt(bpy)(dicnq)](NO3)2 (1) and the qu... more The square-planar heteroleptic Pt(II) coordination compound [Pt(bpy)(dicnq)](NO3)2 (1) and the quaternized dicnq ligand, namely 12,13-dicyano-5,6-dihydrodipyrazino[2,3-f:1′,2′,3′,4′-lmn][1,10]phenanthroline-4,7-diium dibromide (2) (Fig. 1) were synthesized and fully characterized by means of FTIR, NMR, MALDI-TOF MS and the purity was confirmed by CHN analyses. The DNA binding profiles of 1 and 2 were identified in an identical condition. The biological activities of these compounds were investigated by the assays of transcription and replication inhibition, cytotoxic and antimicrobial activity.
The result of this study indicates that, both compounds strongly bind to DNA via intercalation but only 1 has a strong nuclease activity. The coordination compound of dicnq (1) binds to the DNA only slightly stronger than the quaternized form of dicnq (2), and is more potent as an inhibitor of transcription and replication and therefore, 1 has more potential as an anticancer agent but the compounds did not show cytotoxic activity against MCF-7 and MDA-MB-231 breast cancer, and DLD-1 colon cancer cell lines it was found that they only had activities against HepG2 liver cancer cell line with following IC50 values; 94.75 and 159.60 µM for 1 and 2, respectively. In addition, tested bacteria are more susceptible to compound 1. These biological activities of 1 may strongly be due to its ability to digest DNA as a chemical nuclease. According to this study, the quaternization of the ligand does not make biologically more active than the coordination compound of the same ligand in this case. The compound (1) is worth further investigation for its antitumor activities.
Chemical and photo-induced nuclease activity of a novel minor groove DNA binder Cu(II) complex
Journal of the Serbian Chemical Society, 2019
A new type of copper(II) metal complex containing 1,10-phenanthroline (phen) and 8-(difluorometho... more A new type of copper(II) metal complex containing 1,10-phenanthroline (phen) and 8-(difluoromethoxy)-3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazole (dtb) ligands was prepared and characterized. The ds-DNA interaction of the complex was studied by UV–Vis spectrophotometry, competitive fluorometric titration with ethidium bromide (EB) and 4′,6-diamidino-2-phenylindole (DAPI), viscosity measurements and agarose gel electrophoresis. The results show that the complex can bind to ds-DNA in the minor groove by displacing DAPI molecules. DNA cleavage mechanism studies revealed that hydrogen peroxide radicals are responsible for DNA oxidative cleavage.
Applied Organometallic Chemistry, 2019
Novel hydrazone of 3‐hydroxy‐2‐naphthoichydrazide and dehydroacetic acid, and its Ni(II), Cu(II) ... more Novel hydrazone of 3‐hydroxy‐2‐naphthoichydrazide and dehydroacetic acid, and its Ni(II), Cu(II) and Co(II) complexes were synthesized and characterized. The antimicrobial and DNAbinding properties indicated moderateactivity for the complexes. Molecular docking indicated the Cu(II) complex most effective against Gram‐positive (S. aureus) bacteria and cleavage pBR322DNA more efficiently in the presence of H2O2. DFT calculations revealed that Cu(II) complex has asmaller HOMO‐LUMO gap suggesting a higher tendency to donate electrons toelectron accepting species of biological targets.
Synthesis and characterization of Cu(II), Co(II) and Ni(II) complexes of a benzohydrazone derivative: Spectroscopic, DFT, antipathogenic and DNA binding studies
Journal of Molecular Structure, 2019
Co(II), Ni(II) and Cu(II) complexes of a benzohydrazone derivative, obtained by the reaction of d... more Co(II), Ni(II) and Cu(II) complexes of a benzohydrazone derivative, obtained by the reaction of dehydroacetic acid and benzohydrazide, have been synthesized and characterized by conventional spectroscopic techniques, elemental analyses, magnetic susceptibility and conductivity methods, and screened for antibacterial, DNA binding and cleavage properties. Spectroscopic, magnetic and elemental analyses indicated a square planar and a tetrahedral geometries with formula, [M(L)2], for the Ni(II) and Co(II) complexes, respectively, while a tetrahedral geometry of formula, [ML(H2O)2]·CH3COO−, was adopted for the Cu(II) complex. The Ni and Co complexes were non-electrolytes with molar conductance within the range of 11.46–14.01 Ω−1cm2mol−1, while the copper complex was a 1:1 electrolyte in DMSO with a value of 55.11 Ω−1cm2mol−1. The copper complex had the highest antibacterial activity against Staphylococcus aureus (ATCC 29213). DNA cleavage activities of the compounds, evaluated on pBR322 DNA by agarose gel electrophoresis in the presence and absence of peroxide oxidant (H2O2) and free radical scavenger (DMSO), indicated no activity for the ligand, and a moderate activity for the complexes, with the copper complex cleaving more efficiently in the presence of H2O2. Upon evaluating the complexes for antimicrobial and A-DNA activities using molecular docking technique the copper complex was found to be most effective against Gram-positive (S. aureus) bacteria. [CuL(H2O)2]+ showed good interaction with hydrogen bonding with the major-groove (C2.G13 base pair) of A-DNA. Density functional theory (DFT) calculations of structural and electronic properties of complexes revealed that [CuL(H2O)2]+ had a smaller HOMO-LUMO gap, suggesting a higher tendency to donate electrons to electron accepting species of biological targets.
spiro-Cyclotriphosphazenes containing 4-hydroxyphenylethyl pendant arm: Syntheses, structural characterization and DNA interaction study
Inorganica Chimica Acta, 2018
The reaction of hexachlorocyclotriphosphazene, N3P3Cl6, with tyramine podand (2) afforded partly ... more The reaction of hexachlorocyclotriphosphazene, N3P3Cl6, with tyramine podand (2) afforded partly substituted spiro-cyclotriphosphazene (3). Amine-substituted spiro-cyclotriphosphazenes 4a–g were prepared by substitution of the Cl–atoms in 3 with pyrrolidine, piperidine, morpholine, 1,4-dioxa-8-azaspiro[4,5]decane, 1-(2-aminoethyl)pyrrolidine, 1-(2-aminoethyl) piperidine, and 4-(2-aminoethyl)morpholine, respectively. All of the cyclotriphosphazene derivatives were characterized by elemental analysis, FTIR, MS, 1D 1H, 13C and 31P NMR and 2D HSQC techniques, and the crystal structures of 3 and 4b were verified by X-ray diffraction analysis. The relationships δPOPN shifts with exocyclic OPN (α′) and endocyclic NPN (α) bond angles, and electron density transfer parameters Δ(P-N) for spiro-cyclotriphosphazenes were presented. The DNA cleavage activity of cyclotriphosphazene derivatives (3, and 4a–g) was studied on double-stranded pBR322 DNA using gel electrophoresis experiments. It was found that 4e and 4f caused the highest level of DNA damage. The interactions of 3 and 4e with calf thymus DNA were also investigated using absorption spectrometry. The molecular docking was performed to identify the interaction of the compounds (3 and 4b) with the DNA (PDB ID:3V9D for A-DNA and PDB ID:1BNA for B-DNA).
Novel Naphthalimide Derivatives as Selective G-Quadruplex DNA Binders
Applied Biochemistry and Biotechnology, 2018
A new derivate of 4-bromo-1,8-naphthalic anhydride and its quaternized analogue have been prepare... more A new derivate of 4-bromo-1,8-naphthalic anhydride and its quaternized analogue have been prepared and characterized. The interactions of both derivatives with human telomere quadruplex-DNA and ds-DNA have been comparatively studied by UV-visible (UV-Vis), fluorescent intercalator displacement assays, competition dialysis, circular dichroism (CD), agarose gel electrophoresis, and polyacrylamide gel electrophoresis. The results show that both derivatives can stabilize G-quadruplexes DNA, and they show different binding affinities for G-quadruplexes-DNA and ds-DNA. All spectroscopic studies have shown that the derivatives have a modest selectivity for G-quadruplex versus ds-DNA.
DNA binding by copper (II) complexes of semithiocarbazone containing ligands
Bulgarian Chemical Communications, 2017
DNA binding properties of two previously synthesized copper complexes of vic-dioximes bearing thi... more DNA binding properties of two previously synthesized copper complexes of vic-dioximes bearing thiosemicarbazone units (2E)-2-[4-(dimethylamino)benzylidene]-N-[(1Z,2E)-N-hydroxy-2- hydroxyimino)ethanimidoyl]hydrazine carbothioamide (1) and (2E)-2-[4-(diethylamino)benzylidene]-N-[(1Z,2E)-N-hydroxy-2- hydroxyimino)ethanimidoyl] hydrazine carbothioamide (2), were investigated using absorption spectroscopy, fluorescence spectroscopy, and agarose gel electrophoresis methods. Experimental studies suggested that the complexes bind to DNA through intercalation. Their intrinsic binding constants (Kb) were calculated as 1: 5.50 ± 0.25 × 104 M−1; 2: 2.10 ± 0.18 × 105 M−1. These complexes also promote the cleavage of plasmid pBR322, both in the absence and presence of hydrogen peroxide.
Bulgarian Chemical Communications, 2017
Flavonoids: quercitrin, myricitrin and rutin and their metal complexes were comparatively investi... more Flavonoids: quercitrin, myricitrin and rutin and their metal complexes were comparatively investigated for binding to DNA by means of spectrophotometric methods and DNAse activities were evaluated via agarose gel electrophoresis of pBR322. Free flavonoids bind to DNA in an intercalative mode, but Cu(II) complexes of these flavonoids bind even stronger due to the electrostatic interaction of the metal in addition to the intercalation. Flavonoids show protective effect
against DNA cleavage in the presence of peroxide. However, Cu(II) and Zn(II) complexes of these flavonoids cause multiple scissions on the DNA backbone. In addition, Cu(II) complexes of the flavonoids have stronger DNAse activity. Moreover, myricitrin was found two times more cytotoxic when combined with metal ions (Cu2+ or Zn2+) than when used alone against peripheral blood mononuclear cells.
Karaelmas Science and Engineering Journal, 2017
Vic-dioxime ligands and their metal complexes are very important for their biological activities ... more Vic-dioxime ligands and their metal complexes are very important for their biological activities and thoroughly studied. In addition,
several thiosemicarbazone derivatives were synthesized and their potentials as anti-tumor agents were reported. As well as this, Nickel
(II) complexes, among the other metal complexes, have an important proportion in DNA interaction studies. The compounds which have all these features (vic-dioxime, thiosemicarbazone group and Ni(II)) are not evaluated for their interactions with DNA.
DNA interactions of Ni(II) complex of thiosemicarbazone containing vic-dioxime ligand will be studied by using UV titration, fluorescence, and agarose gel electrophoresis methods for the first time.
DNA studies of newly synthesized heteroleptic platinum(II) complexes [Pt(bpy)(iip)] 2+ and [Pt(bpy)(miip)] 2
Journal of Biological Inorganic Chemistry, 2016
1 and 2, respectively. The difference in the DNA-binding affinities of 1 and 2 may presumably be ... more 1 and 2, respectively. The difference in the DNA-binding affinities of 1 and 2 may presumably be explained by the methylated imidazole nitrogen atom that makes the compound more hydrophobic and gives better intercalative binding ability to DNA's hydrophobic environment.
Bulgarian Chemical Communications, 2016
In this study, G-quadruplex DNA (Q-DNA) binding abilities of two platinum complexes ([Pt(bpy)(pip... more In this study, G-quadruplex DNA (Q-DNA) binding abilities of two platinum complexes ([Pt(bpy)(pip)](NO3)2 (1) and [Pt(bpy)(hpip)](NO3)2 (2) (bpy is 2,2ʹ-bipyridine; pip is 2-phenylimidazo[4,5-f][1,10]phenanthroline; hpip is 2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline) those previously reported were compared with double stranded DNA (ds-DNA) binding abilities. The interactions of both derivatives with human telomere Q-DNA (both the antiparallel basket and the mixed-hybrid G-quadruplex) and ds-DNA have been comparatively studied by UV-visible (UV-Vis), fluorescent intercalator displacement (FID) assays and thermal melting methods. The results show that both derivatives can stabilize Q-DNA and they show different binding affinities for different Q-DNA and ds-DNA. All spectroscopic studies have shown that the derivatives have a modest selectivity for Q-DNA vs ds-DNA. Increase in melting temperature was detected for both DNA forms but increase in Q-DNA melting temperature was significantly higher.
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Drug-DNA Interactions by Burak Coban
(btdip)]2+ (1) and [Ni(phen)2(dbfip)]2+ (2)
have been synthesized and characterized by CHN analysis, ESIMS, NMR and UV-vis spectra. Their DNA binding abilities were spectrophotometrically, hydrodynamically and electrophoretically studied and found that while btdip binds DNA externally, dbfip binds in the grooves and both of their nickel complexes also bind DNA through grooves giving severe DNA damage in the presence of peroxide. The compounds were screened against four different human cancer cell lines using MTT assay method. The results obtained showed that both ligands are active against DLD-1, and further dbfip is found to be more active than positive control drugs against DLD-1 and HepG2 cell lines. The complex 2 has more antiproliferative effect than 1 against MCF-7 and HepG2 cells. On the other hand, complex 2 was found to have more toxic effect on HepG2 cells than the standard drugs cisplatin and ploxal-S.
The result of this study indicates that, both compounds strongly bind to DNA via intercalation but only 1 has a strong nuclease activity. The coordination compound of dicnq (1) binds to the DNA only slightly stronger than the quaternized form of dicnq (2), and is more potent as an inhibitor of transcription and replication and therefore, 1 has more potential as an anticancer agent but the compounds did not show cytotoxic activity against MCF-7 and MDA-MB-231 breast cancer, and DLD-1 colon cancer cell lines it was found that they only had activities against HepG2 liver cancer cell line with following IC50 values; 94.75 and 159.60 µM for 1 and 2, respectively. In addition, tested bacteria are more susceptible to compound 1. These biological activities of 1 may strongly be due to its ability to digest DNA as a chemical nuclease. According to this study, the quaternization of the ligand does not make biologically more active than the coordination compound of the same ligand in this case. The compound (1) is worth further investigation for its antitumor activities.
against DNA cleavage in the presence of peroxide. However, Cu(II) and Zn(II) complexes of these flavonoids cause multiple scissions on the DNA backbone. In addition, Cu(II) complexes of the flavonoids have stronger DNAse activity. Moreover, myricitrin was found two times more cytotoxic when combined with metal ions (Cu2+ or Zn2+) than when used alone against peripheral blood mononuclear cells.
several thiosemicarbazone derivatives were synthesized and their potentials as anti-tumor agents were reported. As well as this, Nickel
(II) complexes, among the other metal complexes, have an important proportion in DNA interaction studies. The compounds which have all these features (vic-dioxime, thiosemicarbazone group and Ni(II)) are not evaluated for their interactions with DNA.
DNA interactions of Ni(II) complex of thiosemicarbazone containing vic-dioxime ligand will be studied by using UV titration, fluorescence, and agarose gel electrophoresis methods for the first time.