Synthesis and characterization of two new mixed-ligand Cu(II) complexes of a tridentate NN'O type Schiff base ligand and N-donor heterocyclic co-ligands: In vitro anticancer assay, DNA/human leukemia/COVID-19 molecular docking studies, and pharmacophore modeling.

Two new mixed-ligand complexes with general formula [Cu(SB)(L')]ClO4 (1 and 2) were synthesized and characterized by different spectroscopic and analytical techniques including Fourier transform infrared (FT-IR) and UV-Vis spectroscopy and elemental analyses. The SB ligand is an unsymmetrical tridentate NN'O type Schiff base ligand that was derived from the condensation of 1,2-ethylenediamine and 5-bromo-2-hydroxy-3-nitrobenzaldehyde. The L' ligand is pyridine in (1) and 2,2'-dimethyl-4,4'-bithiazole (BTZ) in (2). Crystal structure of (2) was also obtained. The two complexes were used as anticancer agents against leukemia cancer cell line HL-60 and showed considerable anticancer activity. The anticancer activity of these complexes was comparable with the standard drug 5-fluorouracil (5-FU). Molecular docking and pharmacophore studies were also performed on DNA (PDB:1BNA) and leukemia inhibitor factor (LIF) (PDB:1EMR) to further investigate the anticancer and anti-COVID activity of these complexes. The molecular docking results against DNA revealed that (1) preferentially binds to the major groove of DNA receptor whereas (2) binds to the minor groove. Complex (2) performed better with 1EMR. The experimental and theoretical results showed good correlation. Molecular docking and pharmacophore studies were also applied to study the interactions between the synthesized complexes and SARS-CoV-2 virus receptor protein (PDB ID:6LU7). The results revealed that complex (2) had better interaction than (1), the free ligands (SB and BTZ), and the standard drug favipiravir.

Pharmacological Properties of Pt(II) and Pt(IV) Complexes with 2,2'-Dipyridylamine; the Comparative In Vitro Thereof.

Pt-based drugs such as cisplatin are frontline drugs used for the treatment of different solid malignancies. However, they represent major problems, such as severe side effects and drug resistance. To find out the structure-activity relationship; in this study, Pt(II) and Pt(IV) complexes with similar ligands, namely tetrachloro(2,2'-dipyridylamine)platinum(IV) (1) and dichloro(2,2'-dipyridylamine)platinum(II) (2) were synthesized, tested for their in vitro activity over different tumor cell lines and compared with cisplatin. Despite nontoxicity against nonmalignant cells, both titled compounds depict considerable killing activity over HT-29 cells. So, this cell line is served for further investigation. Cell cycle test revealed that the mechanism of cell cycle arrest induced by complexes 1 and 2 over HT-29 cells was relatively similar and obviously different from cisplatin. Moreover, apoptosis analysis showed that late apoptosis/necrosis is the primary disease for the death of cell by three complexes. Comet assay and colony-forming test were also performed on HT-29 cells whose results were thoroughly discussed.

A Novel Platinum-based Compound with Preferential Cytotoxic Activity against a Panel of Cancer Cell Lines.

PURPOSE: Cisplatin as a platinum (Pt)-based chemotherapeutic compound is commonly applied for the treatment of several types of cancer. Nonetheless, drug resistance and severe adverse effects have been observed upon using cisplatin. Here, we have explored the cytotoxicity of novel Pt-based compounds on several cancer cell lines. METHODS: Five synthetic Pt compounds as well as cisplatin were investigated by XTT assay to determine their cytotoxicity against cell lines originated from prostate, ovary, and breast cancers at different time periods at various concentrations. Additionally, the apoptosis rate in cell lines was determined using flow cytometry. Binding to DNA was investigated through spectrophotometric and viscometric studies. RESULTS: With the exception of one compound, all of the Pt-complexes effectively killed the prostate cancer cell lines (i.e. PC-3 and DU 145). One compound, [Pt(2,2'- dipyridylamine)Cl4].DMF, was chosen as the most potent compound due to its high selective cytotoxic activity and its cytotoxicity was further tested and compared with that of cisplatin on SKOV-3, Caov-4, MDA-MB-231, and MCF7 cell lines. [Pt(2,2'-dipyridylamine)Cl4].DMF had a higher selective cytotoxic capacity in comparison with cisplatin at higher concentrations and longer culture periods. Furthermore, as related to apoptosis induction, treatment with [Pt(2,2'-dipyridylamine)Cl4 ].DMF was significantly more effective than that of cisplatin in five out of six examined cell lines. [Pt(2,2'-dipyridylamine)Cl4].DMF was shown to intercalate into DNA. CONCLUSIONS: The current study introduced a novel Pt-based complex with highly selective and potent in vitro anti-tumor impacts superior to those of cisplatin, a conventional chemotherapeutic agent. [Pt (2,2'-dipyridylamine)Cl4].DMF could be regarded as a promising antitumor agent in future investigations.

A Novel Platinum-based Compound with Preferential Cytotoxic Activity against a Panel of Cancer Cell Lines

PURPOSE: Cisplatin as a platinum (Pt)-based chemotherapeutic compound is commonly applied for the treatment of several types of cancer. Nonetheless, drug resistance and severe adverse effects have been observed upon using cisplatin. Here, we have explored the cytotoxicity of novel Pt-based compounds on several cancer cell lines. METHODS: Five synthetic Pt compounds as well as cisplatin were investigated by XTT assay to determine their cytotoxicity against cell lines originated from prostate, ovary, and breast cancers at different time periods at various concentrations. Additionally, the apoptosis rate in cell lines was determined using flow cytometry. Binding to DNA was investigated through spectrophotometric and viscometric studies. RESULTS: With the exception of one compound, all of the Pt-complexes effectively killed the prostate cancer cell lines (i.e. PC-3 and DU 145). One compound, [Pt(2,2'- dipyridylamine)Cl4].DMF, was chosen as the most potent compound due to its high selective cytotoxic activity and its cytotoxicity was further tested and compared with that of cisplatin on SKOV-3, Caov-4, MDA-MB-231, and MCF7 cell lines. [Pt(2,2'-dipyridylamine)Cl4].DMF had a higher selective cytotoxic capacity in comparison with cisplatin at higher concentrations and longer culture periods. Furthermore, as related to apoptosis induction, treatment with [Pt(2,2'-dipyridylamine)Cl4 ].DMF was significantly more effective than that of cisplatin in five out of six examined cell lines. [Pt(2,2'-dipyridylamine)Cl4].DMF was shown to intercalate into DNA. CONCLUSIONS: The current study introduced a novel Pt-based complex with highly selective and potent in vitro anti-tumor impacts superior to those of cisplatin, a conventional chemotherapeutic agent. [Pt (2,2'-dipyridylamine)Cl4].DMF could be regarded as a promising anti-tumor agent in future investigations.

Polybutylcyanoacrylate nanoparticles and drugs of the platinum family: last status.

Cisplatinum and carboplatinum drugs from platinum-containing family are anti-cancer drugs. Using these drugs causes side effects. Targeted and selective prescription decreases side effects of the drugs. This can be achieved using nanotechnology. In this study, cisplatinum and carboplatinum drugs were loaded on polybutylcyanoacrylate nanoparticles using emulsion polymerization method. To determine amount of loaded drug onto nanoparticle, spectrophotometry method was used. Evaluation of cytotoxicity of such nanoparticles was performed on MCF-7 cell line using MTT assay. Loading percentage of cisplatinum and carboplatinum drugs on nanoparticles were estimated 4 and 6 %, respectively. Cytotoxicity survival rate for cisplatinum and nanoparticle containing cisplatinum at the lowest concentration (p < 0.01) (20 µM) were estimated 64 ± 1 and 67 ± 0.5 %, respectively. These values at the highest concentration (p < 0.01) (160 µM) were measured 28 ± 0.7 and 31 ± 0.4 %. Additionally for carboplatinum and nanoparticles containing carboplatinum at the concentration (p < 0.01) (20 µM) amounts were estimated to be 80 ± 0.6 and 84 ± 0.6 %, while at the concentration (p < 0.01) (160 µM) were identified to be 44 ± 0.5 and 51 ± 0.2 %, respectively. Probably, due to low level of loading, cytotoxicity of both drugs at nano particle status was decreased in comparison with their standard form.

The influence of steric effects on intramolecular secondary bonding interactions; cytotoxicity in gold(III) bithiazole complexes.

The reaction of two sterically different bithiazole ligands with gold(III) was investigated. Our results show that, depending on the ligand used, different coordination geometries around the gold(III) center were achieved. Where sterically unhindered 4bt ligand was used, regular square-planar compound [Au(4bt)Cl2][AuCl4] (1) is isolated, while in the case of sterically hindered dm4bt ligand, the interplay between the steric effect and the intramolecular secondary bonding interaction leads to the formation of disordered square-pyramidal geometry in [Au(dm4bt)Cl3] (2). Furthermore, the steric influence of the methyl group in the ligand plays an important role in the cytotoxicity of the compound in different cultures. Interestingly, compound 1 is more potent to kill a breast cancer cell line than cisplatin (13 times), and its cytotoxicity arises from the cationic part, [Au(4bt)Cl2](+).

6,6'-Dimethyl-2,2'-bipyridin-1-ium tetra-chloridoaurate(III).

In the anion of the title compound, (C(12)H(13)N(2))[AuCl(4)], the Au(III) atom has a square-planar coordination. In the crystal, inter-molecular N-H⋯Cl and C-H⋯Cl hydrogen bonds and π-π contacts between the pyridine rings [centroid-centroid distance = 3.5419 (19) Å] result in the formation of a supra-molecular structure.

2,5-Bis(pyridinium-2-yl)-3,6-bis-(2-pyrid-yl)pyrazine bis-[tetra-chlorido-aurate(III)].

In the title compound, (C(24)H(18)N(6))[AuCl(4)](2), the cation is located on an inversion center. Each of the two independent Au(III) ions lies on an inversion center and has a distorted square-planar geometry. In the crystal, inter-molecular C-H⋯Cl hydrogen bonds, π-π inter-actions [centroid-centroid distances = 3.5548 (16) and 3.7507 (16) Å] and Au⋯π inter-actions [Au⋯centroid distance = 3.6424 (10) Å] are effective in the stabilization of the structure, resulting in the formation of a supra-molecular structure. Intra-molecular N-H⋯N hydrogen bonds are present in the cation.

catena-Poly[[(2,2'-dimethyl-4,4'-bi-1,3-thia-zole-κN,N')cadmium]-di-µ-bromido].

In the title coordination polymer, [CdBr(2)(C(8)H(8)N(2)S(2))](n), the Cd(II) atom is six-coordinated in a distorted octa-hedral geometry by two N atoms from a 2,2'-dimethyl-4,4'-bi-1,3-thia-zole ligand and four bridging Br atoms. The bridging function of the Br atoms leads to a chain structure along [100]. Inter-chain C-H⋯Br hydrogen bonds and π-π contacts between the thia-zole rings [centroid-centroid distances = 3.810 (5) and 3.679 (5) Å] are observed.

Synthesis, characterization, mechanochromism and photochromism of [Fe(dm4bt)3][FeCl4]2 and [Fe(dm4bt)3][FeBr4]2, along with the investigation of steric influence on spin state.

The complexes [Fe(dm4bt)(3)][FeCl(4)](2) (1) and [Fe(dm4bt)(3)][FeBr(4)](2) (2) were prepared from the reaction of 2,2'-dimethyl-4,4'-bithiazole (dm4bt) with FeCl(3)·6H(2)O and FeBr(3), respectively, in methanol. Both complexes were characterized by IR, UV-Vis and (1)H NMR spectroscopy and their structures were studied by single-crystal diffraction. The methylated bithiazole led to high spin Fe(II) centers in the octahedral cation part of complexes 1 and 2 with Fe-N distance of 2.220 Å, in spite of the low spin octahedral Fe(II) complexes with unsubstituted bithiazole ligands. Crystal structure determination of 2 was performed at 90, 120 and 298 K. Temperature reduction to 90 K resulted in a decrease in the Fe-N bond length to 2.206 Å which is still in the range of high spin Fe(II). Complex 1 shows a reversible mechanochromic effect from the crystalline phase to powder form from red to yellow; it also displays reversible photochromism from yellow to green in solution under sunlight. The magnetic behaviour of the complexes was also studied at 2-300 K. The temperature dependence of χ(m)T curves for the two forms of 1, crystal and powder, demands some changes in their magnetic behavior, causing different colors i.e. red and yellow. At low temperatures, χ(m)T decreases where the decrease starts at around 65 K for compound 1, and at around 100 K for compound 2, due to different counterions. The two complexes exhibit antiferromagnetism at around 4 K.

Tris(4,4'-bi-1,3-thia-zole-κN,N')iron(II) tetra-bromidoferrate(III) bromide.

In the [Fe(4,4'-bit)(3)](2+) (4,4'-bit is 4,4'-bi-1,3-thia-zole) cation of the title compound, [Fe(C(6)H(4)N(2)S(2))(3)][FeBr(4)]Br, the Fe(II) atom (3 symmetry) is six-coordinated in a distorted octa-hedral geometry by six N atoms from three 4,4'-bit ligands. In the [FeBr(4)](-) anion, the Fe(III) atom (3 symmetry) is four-coordinated in a distorted tetra-hedral geometry. In the crystal, inter-molecular C-H⋯Br hydrogen bonds and Br⋯π inter-actions [Br⋯centroid distances = 3.562 (3) and 3.765 (2) Å] link the cations and anions, stabilizing the structure.

(2,2'-Dimethyl-4,4'-bi-1,3-thia-zole-κN,N')diiodidomercury(II).

In the title compound, [HgI(2)(C(8)H(8)N(2)S(2))], the Hg(II) atom is four-coordinated in a distorted tetra-hedral geometry by two N atoms from a 2,2'-dimethyl-4,4'-bithia-zole ligand and two I atoms. In the crystal structure, adjacent mol-ecules are connected by π-π contacts between the thia-zole rings [centroid-centroid distance = 3.591 (3) Å].

Dibromido(2,2'-dimethyl-4,4'-bi-1,3-thia-zole-κN,N')mercury(II).

The asymmetric unit of the title compound, [HgBr(2)(C(8)H(8)N(2)S(2))], contains two crystallographically independent mol-ecules. The Hg(II) atoms are four-coordinated in a distorted tetra-hedral geometry by two N atoms from a 2,2'-dimethyl-4,4'-bi-1,3-thia-zole ligand and two Br atoms. In the crystal structure, inter-molecular C-H⋯Br hydrogen bonds and π-π contacts between the thia-zole rings [centroid-centroid distances = 3.670 (3) and 3.614 (2) Å] stabilize the structure.

Bis(phenanthridinium) hexa-chloridoplatinate(IV) dimethyl sulfoxide disolvate.

The asymmetric unit of the title compound, (C(13)H(10)N)(2)[PtCl(6)]·2C(2)H(6)OS, contains one independent protonated phenanthridinium cation, half of a centrosymmetric [PtCl(6)](2-)anion and one dimethyl sulfoxide solvent mol-ecule. Intra-molecular N-H⋯O and inter-molecular C-H⋯Cl hydrogen-bonding inter-actions seem to be effective in the stabilization of the structure.

Bis[dichlorido(5,5'-dimethyl-2,2'-bi-pyridine-κN,N')gold(III)] tetra-chlorido-aurate(III) dichloridooaurate(I).

The title compound, [Au(III)Cl(2)(C(12)H(12)N(2))](2)[Au(III)Cl(4)][Au(I)Cl(2)], contains three distinct types of Au atom. In the cation, the Au(III) atom is four-coordinated in a distorted square-planar arrangement by an N,N'-bidentate 5,5'-dimethyl-2,2'-bipyridine ligand and two terminal Cl atoms. In the [AuCl(4)](-) anion, the centrosymmetric Au(III) atom has a square-planar coordination. The centrosymmetric [AuCl(2)](-) anion is linear. Intra- and inter-molecular C-H⋯Cl hydrogen bonds help to establish the conformation and packing.

(2,2'-Dimethyl-4,4'-bi-1,3-thia-zole-κN,N')bis(thio-cyanato-κS)mercury(II).

The Hg(II) atom in the title compound, [Hg(SCN)(2)(C(8)H(8)N(2)S(2))], is chelated by the bidentate heterocycle through the N atoms and is coordinated by the S atoms of two thiocyanate anions, resulting in a considerably distorted tetra-hedral coordination geometry.

2,9-Dimethyl-4,7-diphenyl-1,10-phenanthrolin-1-ium tetra-chloridoaurate(III).

Both the cation and anion of the title compound, (C(26)H(21)N(2))[AuCl(4)], are disposed about a plane of mirror symmetry. The 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinium ring is oriented at a dihedral angle of 44.2 (1)° with respect to the planar phenyl ring systems. The Au(III) atom has a square-planar environment defined by four Cl atoms. The crystal structure is stabilized by C-H⋯π and Au⋯π ring-metal (3.551 Å) inter-actions. In the crystal structure, the mol-ecules stack along the c axis via N-H⋯N hydrogen-bond inter-actions.

Bis(2,4,6-trimethyl-pyridinium) hexa-chloridoplatinate(IV).

The asymmetric unit of the title compound, (C(8)H(12)N)(2)[PtCl(6)], contains one independent protonated 2,4,6-trimethyl-pyridinium cation and one half of a centrosymmetric [PtCl(6)](2-) anion. The Pt ion has an almost ideal octa-hedral coordination. In the crystal structure, intra-molecular N-H⋯Cl and inter-molecular C-H⋯Cl hydrogen bonds result in the formation of a supra-molecular structure.

(5,5'-Dimethyl-2,2'-bipyridine-κN,N')diiodidomercury(II).

In the mol-ecule of the title compound, [HgI(2)(C(12)H(12)N(2))], the Hg(II) atom is four-coordinated in a distorted tetra-hedral configuration by two N atoms from 5,5'-dimethyl-2,2'-bipyridine and two I atoms. There is a π-π contact between pyridine rings of adjacent molecules [centroid-centroid distance = 3.723 (5) Å].

Trichlorido(4,4'-dimethyl-2,2'-bipyridine-κN,N')(dimethyl sulfoxide-κO)indium(III).

In the mol-ecule of the title compound, [InCl(3)(C(12)H(12)N(2))(C(2)H(6)OS)], the In(III) atom is six-coordinated in a distorted octa-hedral configuration by two N atoms from the chelating 4,4'-dimethyl-2,2'-bipyridine ligand, one O atom from dimethyl sulfoxide and three Cl atoms. In the crystal structure, inter-molecular C-H⋯Cl hydrogen bonds link the mol-ecules into centrosymmetric dimers.