13601-02-0Relevant articles and documents
Improving of Anticancer Activity and Solubility of Cisplatin by Methylglycine and Methyl Amine Ligands Against Human Breast Adenocarcinoma Cell Line
Shams Abyaneh, Fatemeh Safa,Eslami Moghadam, Mahboube,Divsalar, Adeleh,Ajloo, Davood,Hosaini Sadr, Moyaed
, p. 271 - 291 (2018)
Methylglycine, also known sarcosine, is dramatically used in drug molecules and its metal complexes can interact to DNA and also do cleavage. Hence, to study the influence of methylglycine ligand on biological behavior of metal complexes, two water-solubl
Biodegradable block copolymer scaffolds for loading and delivering cisplatin anticancer drug
Surnar, Bapurao,Subash, Pramod P.,Jayakannan, Manickam
, p. 1119 - 1126 (2014)
A carboxylic acid substituted amphiphilic diblock copolymer scaffold with a hydrophilic PEG-chain and hydrophobic biodegradable poly(caprolactone) (PCL), which forms a cisplatin anticancer drug is reported herein. Cisplatin [cis-dichloro-diammine platinum(II), CDDP] was anchored on the polymer backbone through Pt-OOC-PCL chemical linkage that enabled self-assembly of the prodrug to produce 110±10 nm nanoparticles in water. These drug loaded nanoparticles were characterized by dynamic light scattering, electron microscopy, and X-ray diffraction. The polymer-drug conjugate burst instantaneously in saline and PBS to release 35% of the cisplatin drug for immediate administration. The remaining drug that retained in the polymer scaffold underwent slow and controlled release to deliver the drug over a period of 6-7 d. In the presence of esterase enzyme; the biodegradable PCL aliphatic ester backbone broke completely to release 100% loaded drugs within a few hours. This biodegradable diblock copolymer design strategy opens up new platform for cisplatin-polymer drug delivery approach. Copyright
Kinetic and Thermodynamic Investigation of Human Serum Albumin Interaction with Anticancer Glycine Derivative of Platinum Complex by Using Spectroscopic Methods and Molecular Docking
Shiekhzadeh, Afrooz,Sohrabi, Nasrin,Moghadam, Mahboube Eslami,Oftadeh, Mohsen
, p. 506 - 528 (2020)
In this paper, a new anticancer Pt (II) complex, cis-[Pt (NH3)2(tertpentylgly)]NO3, was synthesized with glycine-derivative ligand and characterized. Cytotoxicity of this water-soluble Pt complex was studied against human cancer breast cell line of MCF-7. The interaction of human serum albumin (HSA) with Pt complex was studied by using UV-Vis, fluorescence spectroscopy methods, and molecular docking at 27 and 37?°C in the physiological situation (I = 10?mM, pH = 7.4). The negative ΔHb0 and positive ΔSb0 indicated that electrostatic force may be a major mode in the binding between Pt complex and HSA. Binding constant values were obtained through UV-Vis and fluorescence spectroscopy that reveal strong interaction. The negative Gibbs free energy that was obtained by using the UV-Vis method offers spontaneous interaction. Fluorescence quenching the intensity of HSA by adding Pt complex confirms the static mode of interaction is effective for this binding process. Hill coefficients, nH, Hill constant, kH, complex aggregation number around HSA, , number of binding sites, g, HSA melting temperature, Tm, and Stern-Volmer constant, kSV, were also obtained. The kinetics of the interaction was studied, which showed a second-order kinetic. The results of molecular docking demonstrate the position of binding of Pt complex on HSA is the site I in the subdomain IIA.
Ferrocenyl-bipyridinium cations and their platinum complexes related to viologens - Preparation, redox properties, and crystal structures
Mochida, Tomoyuki,Funasako, Yusuke,Nezu, Yukiko,Hagiwara, Koji,Horikoshi, Ryo
, p. 2330 - 2337 (2015)
N-R1-N-R2-4,4'-Bipyridinium and N-R1-4,4'-bipyridinium salts containing ferrocenyl substituents were prepared as donor-acceptor compounds (R1 = ferrocenyl, ferrocenylphenyl; R2 = ferrocenyl, ferroceny
Palladium and platinum complexes of folic acid as new drug delivery systems for treatment of breast cancer cells
He, Chenyang,Heidari Majd, Mostafa,Shiri, Fereshteh,Shahraki, Somaye
, (2021)
Cisplatin is administrated as an agent in treatment of various cancers by intercalation between DNA strands and inhibition of DNA replication. Among the various factors, two important reasons like inhibition of apoptosis by anti-apoptotic mechanisms and i
Cisplatin-Stitched Polysaccharide Vesicles for Synergistic Cancer Therapy of Triple Antagonistic Drugs
Deshpande, Nilesh Umakant,Jayakannan, Manickam
, p. 113 - 126 (2017)
New cisplatin-stitched polysaccharide vesicular nanocarrier is developed for combination therapy of three clinical important antagonistic drugs together to accomplish synergistic cancer therapy in breast cancer treatment. Carboxylic functionalized dextran was tailor-made for the chemical conjugation of cisplatin, and a renewable hydrophobic unit was anchored in the backbone to interdigitize the chains to self-assemble as cisplatin-stitched polysaccharide nanovesicles. Water-soluble DNA-intercalating drug doxorubicin·HCl (DOX) and water insoluble topoisomerase type I inhibitor drug camptothecin (CPT) were encapsulated in these vesicles to produce dual or triple drug-loaded vesicular nanocarrier. This unique cisplatin, DOX and CPT triple drug-loaded dextran vesicles were stable in aqueous medium, and the vesicular geometry acted as a shield for Pt-polymer drug conjugate against glutathione (GSH) detoxification under physiological conditions. Lysosomal enzymes ruptured the nanovesicle exclusively at the intracellular compartments to deliver the combination of all three drugs simultaneously to maximize the therapeutic efficacies. In vitro cytotoxicity studies revealed that free cisplatin was highly detoxified by the GSH in breast cancer cells, whereas the enhanced stability of Pt-stitched dextran vesicle against GSH facilitated ~99% cell killing in breast cancer cells. Combination therapy studies revealed that the free cisplatin, DOX, and CPT were found to be antagonistic to each other. Dual drug-loaded vesicles exhibited synergistic cancer cell killing while delivering these antagonistic drugs from a dextran vesicular platform. Remarkable synergistic cell killing was accomplished in cisplatin, DOX, and CPT triple drug-loaded vesicles at nanogram concentrations in breast cancer cells. The internalization of drugs and cellular uptake were confirmed by confocal microscope and flow cytometry analysis. The drugs were taken by the cancer cells in large amounts while delivering them from dextran vesicles compared to their free form. These spectacular results opened new opportunities for synergistic cancer therapy for GSH-overexpressed breast cancer using triple drug-loaded polysaccharide vesicular nanocarriers.
Synthesis, characterization and anticancer evaluation of transplatin derivatives with heterocyclic thiones
Jomaa, Mohammed Y.,Altaf, Muhammad,Ahmad, Saeed,Alhoshani, Ali,Baig, Nadeem,Kawde, Abdel-Nasser,Bhatia, Gaurav,Singh, Jatinder,Isab, Anvarhusein A.
, p. 360 - 368 (2018)
Platinum(II) complexes of heterocyclic thiones (L) based on transplatin having the general formula, trans-[Pt(NH3)2(Thione)2](NO3)2 have been synthesized and characterized using elemental analysis, IR, and NMR (1H & 13C) spectroscopy. The crystal structures of two of them, trans-[Pt(NH3)2(Imt)2](NO3)2 (1) and trans-[Pt(NH3)2(Me2Imt)2](NO3)2 (3) were determined by X-ray crystallography. The structures of 1 and 3 consist of trans-[Pt(NH3)2L2]2+ complex ions and nitrate counter ions. The platinum atom in both the complex ions adopts a distorted square planar geometry. The spectroscopic data indicated the coordination of thione ligands to platinum(II). The in vitro cytotoxicity of these compounds as well as of cisplatin and carboplatin was investigated using MTT assay against three human cancer cell lines, which are; A549 (lung carcinoma), MCF-7 (breast carcinoma) and HTC15 (colon cancer). The in vitro cytotoxicity in several cases is comparable or even higher, than carboplatin and in two cases than cisplatin.
Novel antitumor cisplatin and transplatin derivatives containing 1-methyl-7-azaindole: Synthesis, characterization, and cellular responses
Pracharova, Jitka,Saltarella, Teresa,Radosova Muchova, Tereza,Scintilla, Simone,Novohradsky, Vojtech,Novakova, Olga,Intini, Francesco P.,Pacifico, Concetta,Natile, Giovanni,Ilik, Petr,Brabec, Viktor,Kasparkova, Jana
, p. 847 - 859 (2015)
The current work investigates the effect of new bifunctional and mononuclear Pt(II) compounds, the cis- and trans-isomers of [PtCl2(NH3)(L)] (L = 1-methyl-7-azaindole, compounds 1 and 2, respectively), on growth and viability of huma
Exploring the DNA binding/cleavage, cellular accumulation and topoisomerase inhibition of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases and their platinum(II) complexes
Neves, Amanda P.,Pereira, Michelle X.G.,Peterson, Erica J.,Kipping, Ralph,Vargas, Maria D.,Silva-Jr, Floriano P.,Carneiro, J. Walkimar M.,Farrell, Nicholas P.
, p. 54 - 64 (2013)
Several chlorido and amino Pt2 + complexes of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases HL exhibiting moderate to high cytotoxicity against cancer cell lines were studied in order to investigate their modes of DNA binding, in vitro DNA strand breaks, mechanism of topoisomerase (Topo I) inhibition and cellular accumulation. DNA model base studies have shown that complex 1a [Pt(HL1)Cl2] was capable of binding covalently to 9-ethylguanine (9-EtG) and 5′-GMP. 1H NMR and mass spectrometry studies have shown that both chlorides were substituted by 9-EtG ligands, whereas 5′-GMP was able to replace only one chlorido ligand, due to steric hindrance. The chlorido Pt2 + complexes [Pt(HL)Cl2] highly accumulate in prostate (PC-3) and melanoma (MDA-MB-435) cell lines, being able to induce DNA strand breaks in vitro and inhibit Topo I by a catalytic mode. On the other hand, the free 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones HL and the amino Pt2 + complexes [Pt(L-)(NH3)2]NO3 neither cause DNA strand breakage nor exhibit strong DNA interaction, nevertheless the latter were also found to be catalytic inhibitors of Topo I at 100 μM. Thus, coordination of the Mannich bases HL to the PtCl2 fragment substantially affects the chemical and biophysical properties of the pro-ligands, leading to an improvement of their DNA binding properties and generating compounds that cleave DNA and catalytically inhibit Topo I. Finally, the high cytotoxicity exhibited by the free (uncomplexed) 2-hydroxy-3- (aminomethyl)-1,4-naphthoquinones might be associated with their decomposition in solution, which is not observed for the Pt2 + complexes.
Effect of Presence of Aliphatic Glycine in the Anti-cancer Platinum Complex Structure on Human Serum Albumin Binding
Shiekhzadeh, Afrooz,Sohrabi, Nasrin,Eslami Moghadam, Mahboube,Oftadeh, Mohsen,Divsalar, Adeleh
, p. 353 - 365 (2022)
Purpose: In this work, a new water-soluble Pt(II) complex was synthesized with aliphatic glycine ligand with a formula of cis-[Pt(NH3)2(isopentylgly)]NO3,?as an anti-cancer drug, and characterized. To determine the binding constant of the human serum albumin (HSA, the most abundant carrier proteins in the?human circulatory system) to this complex and the binding site of the complex on HSA, the melting point of HSA and the kinetics of this interaction were?investigated to introduce an anti-breast cancer drug with fewer side effects. Methods: HSA interaction with the complex was studied via a spectroscopic method at 27 and 37?°C and physiological situation (I = 10?mM, pH = 7.4) and molecular docking. Results: The toxicity value of this complex was obtained against the human cancer breast cell line of MCF-7. The thermodynamic parameters of enthalpy and entropy were also achieved in the empirical procedure. Due to the spontaneity of the interaction, Gibbs free energy variation was obtained negative. The binding constant of this complex to HSA was 3.9 × 105 (M?1). Empirical results showed that the quenching mechanism was static. Hill coefficients, Hill constant, complex aggregation number around protein, number of binding sites, and protein melting temperature with complex were obtained. The kinetics of this interaction was also investigated, which showed that this interaction follows a second-order kinetic. The molecular docking data indicated that the position of the interaction of complex on the protein was the site I in the sub-second IIA. Also, the hydrogen bonding and the hydrophobic interaction as the dominant binding forces were seen in complex–HSA formation. Conclusion: This interaction with positive cooperativity was recognized via a superior hydrogen bond. The reasonable binding constant was also obtained, which could ultimately be a good option as an anti–breast cancer drug.