Synthesis and Biological Characterization of Monomeric and Tetrameric RGD-Cryptophycin Conjugates

The effective delivery of cytotoxic agents to tumor cells is a key challenge in anticancer therapy. Multivalent integrinspecific ligands are considered a promising tool to increase the binding affinity, selectivity, and internalization efficiency of small-molecule drug conjugates. Herein, we report the synthesis and biological evaluation of a multimeric conjugate containing the high-affinity integrin α_vβ₃ binding ligand RAFT-c(RGDfK)₄, a lysosomally cleavable Val-Cit linker, and cryptophycin-55 glycinate, a potent inhibitor of tubulin polymerization. In vitro cytotoxicity assays verified that the multimeric RGD-cryptophycin conjugate displays improved potency compared to the monomeric analogue in integrin α_vβ₃ overexpressing tumor cell lines, while significantly reduced activity was observed in the integrin-negative cell line.     

Linker Hydrophilicity Modulates the Anticancer Activity of RGD–Cryptophycin Conjugates

Most anticancer agents are hydrophobic and can easily penetrate the tumor cell membrane by passive diffusion. This may impede the development of highly effective and tumor-selective treatment options. A hydrophilic β-glucuronidase-cleavable linker was used to connect the highly potent antimitotic agent cryptophycin-55 glycinate with the α_vβ₃ integrin ligand c(RGDfK). Incorporation of the self-immolative linker containing glucuronic acid results in lower cytotoxicity than that of the free payload, suggesting that hydrophilic sugar linkers can preclude passive cellular uptake. In vitro drug-release studies and cytotoxicity assays demonstrated the potential of this small molecule–drug conjugate, providing guidance for the development of therapeutics containing hydrophobic anticancer drugs.     

Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers

Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the α_vβ₃‐integrin ligand cyclo[DKP–RGD]‐CH₂NH₂ ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified α_Vβ₃‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (α_Vβ₃?) and its subclone CCRF‐CEM α_Vβ₃ (α_Vβ₃+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM α_Vβ₃ versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload.     

Imine‐N‐Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p‐Cymene Anticancer Complexes: A Structure–Activity Relationship Study

A family of novel imine‐N‐heterocyclic carbene ruthenium(II) complexes of the general formula [(η⁶‐p‐cymene)Ru(C^N)Cl]PF₆⁻ (where C^N is an imine‐N‐heterocyclic carbene chelating ligand with varying substituents) have been prepared and characterized. In this imine‐N‐heterocyclic carbene chelating ligand framework, there are three potential sites that can be modified, which distinguishes this class of ligand and provides a body of flexibilities and opportunities to tune the cytotoxicity of these ruthenium(II) complexes. The influence of substituent effects of three tunable domains on the anticancer activity and catalytic ability in converting coenzyme NADH to NAD⁺ is investigated. This family of complexes displays an exceedingly distinct anticancer activity against A549 cancer cells, despite their close structural similarity. Complex 9 shows the highest anticancer activity in this series against A549 cancer cells (IC₅₀=14.36 μm ), with an approximately 1.5‐fold better activity than the clinical platinum drug cisplatin (IC₅₀=21.30 μm ) in A549 cancer cells. Mechanistic studies reveal that complex 9 mediates cell death mainly through cell stress, including cell cycle arrest, inducing apoptosis, increasing intracellular reactive oxygen species (ROS) levels, and depolarization of the mitochondrial membrane potential (MMP). Furthermore, lysosomal damage is also detected by confocal microscopy.     

A new Dy(III)-based metal-organic framework with polar pores for pH-controlled anticancer drug delivery and inhibiting human osteosarcoma cells

Anticancer drug delivery is considered as the most common and patient acceptable drug administration with reduced side effects. In general, an ideal drug carrier for anticancer drug delivery should have high drug loading capacity, good biocompatibility, and avoid drug delivery in normal tissue (neutral conditions) and promoting the drug release in cancerous tissue (acidic condition). Herein, we synthesize a new porous Dy(III)-based metal-organic framework, [Dy(HABA)(ABA)](DMA)₄] (1, H₂ABA = 4,4'-azanediyldibenzoic acid, DMA = N,N-dimethylacetamide) with uncoordinated N donor sites in the porous surroundings using a bent polycarboxylic acid linker under solvothermal conditions. The structure of the obtained crystalline product has been determined by X-ray single-crystal diffraction, elemental analysis, TGA, XRD, and gas sorption measurement. Due to the suitable window size and polar atom functionalized 1D channels, the activated 1 (1a) was used for anticancer drug 5-Fu loading. A moderately high drug loading and pH-dependent drug-release behavior could be observed for 1a. Furthermore, as demonstrated by the MTT assay, this drug/MOF composite shows low cytotoxicity, good biocompatibility, and anticancer activity against human osteosarcoma cell lines MG63.     

Cathepsin B‐Specific Metabolic Precursor for In Vivo Tumor‐Specific Fluorescence Imaging

Recently, metabolic glycoengineering with bioorthogonal click reactions has focused on improving the tumor targeting efficiency of nanoparticles as delivery vehicles for anticancer drugs or imaging agents. It is the key technique for developing tumor‐specific metabolic precursors that can generate unnatural glycans on the tumor‐cell surface. A cathepsin B‐specific cleavable substrate (KGRR) conjugated with triacetylated N‐azidoacetyl‐d ‐mannosamine (RR‐S‐Ac₃ManNAz) was developed to enable tumor cells to generate unnatural glycans that contain azide groups. The generation of azide groups on the tumor cell surface was exogenously and specifically controlled by the amount of RR‐S‐Ac₃ManNAz that was fed to target tumor cells. Moreover, unnatural glycans on the tumor cell surface were conjugated with near infrared fluorescence (NIRF) dye‐labeled molecules by a bioorthogonal click reaction in cell cultures and in tumor‐bearing mice. Therefore, our RR‐S‐Ac₃ManNAz is promising for research in tumor‐specific imaging or drug delivery.     

New mononuclear diorganotin(IV) dithiocarboxylates: synthesis,characterization and study of their cytotoxic activities

Since organotin complexes have been reported to show fewer side effects relative to other heavy metal anticancer compounds, in the present study we report for the first time four novel organotin(IV) derivatives with the general formula R₂SnL₂, where R = methyl (1), n‐butyl (2), phenyl (3), benzyl (4) and L = morpholine‐1‐carbodithioate (MCDT). The newly synthesized ligand was monodentate or bidentate, coordinating through a sulfur atom. The complexes were synthesized by directly mixing, refluxing and stirring the ligand, with diorganotin(IV) dichlorides in a suitable solvent. The complexes were found to be pure and their solid and solution phase structural configuration was investigated by FT‐IR, multinuclear NMR (¹ H, ¹³ C, ¹¹⁹Sn) and mass spectrometry. Complex 2 was also studied for its thermal decomposition by thermogravimetry and differential thermal analysis. The results obtained on the basis of these techniques are in full concurrence with the proposed 1:2 (Sn:L) stoichiometry. The cytotoxic activity of the MCDT and diorganotin(IV) complexes (1–4) was tested against tumor cell lines – human cervix carcinoma HeLa and human myelogenous leukemia K562 – and normal immunocompetent cells: peripheral blood mononuclear cells PBMC. Results of bioassay demonstrated that organotin derivatives were in general more active than the anticancer drug cisplatin. Copyright © 2012 John Wiley & Sons, Ltd.     

A Trimodal Closomer Drug‐Delivery System Tailored with Tracing and Targeting Capabilities

The construction and application of a unique monodisperse closomer drug‐delivery system (CDDS) integrating three different functionalities onto an icosahedral closo‐dodecaborane [B₁₂]^2? scaffold is described. Eleven B‐OH vertices of [closo‐B₁₂(OH)₁₂]^2? were used to attach eleven copies of the anticancer drug chlorambucil and the targeting vector glucosamine through a bifurcating lysine linker. The remaining twelfth vertex was used to attach a fluorescent imaging probe. The presence of multiple glucosamine units offered a monodisperse and highly water‐soluble CDDS with a high payload of therapeutic cargo. This array enhanced the penetration of the drug into cancer cells by exploiting the overexpression of GLUT‐1 receptors present on cancer cells. About 15‐fold enhancement in cytotoxicity was observed for CDDS‐1 against Jurkat cells, compared to CDDS‐2, which lacks the GLUT‐1 targeting glucosamine. A cytotoxicity comparison of CDDS‐1 against colorectal RKO cells and its GLUT‐1 knock‐out version confirmed that GLUT‐1 mediates endocytosis. Using fluorescent markers both CDDS‐1 and ‐2 were traced to the mitochondria, a novel target for alkylating agents.     

New Ni(II), Pd(II) and Pt(II) complexes coordinated to azo pyrazolone ligand with a potent anti‐tumor activity: Synthesis,characterization, DFT and DNA cleavage studies

The absolute necessity to fight some class of tumor is perceived as serious health concerns, so the discovery and development of effective anticancer agents are urgently needed. (E)‐4‐((2‐hydroxyphenyl)diazenyl)‐3‐phenyl‐1H‐pyrazol‐5(4H)‐one, HL, and its Ni(II), Pd(II) and Pt(II) complexes were synthesized and the biological activity was evaluated for antitumor, antioxidant and antimicrobial activity as well as DNA cleavage. Their structures were assigned depending on the elemental analysis, conductivity, magnetic moment, spectral measurements (IR, ¹HNMR, mass and UV–Vis) and thermal analysis. 3D molecular modeling using DFT method confirmed that the geometrical structures agree well with the suggested experimental ones. The antitumor activity was evaluated against four different cell lines using MTT assay. The ligand HL showed a potent cytotoxic activity compared to 5‐fluorouracil as a reference drug. For metal complexes, the order of activity was: Pd(II) > Ni(II) > Pt(II). A remarkable antioxidant activity for the ligand HL was recorded. It was higher than that of the metal complexes. Results of antimicrobial experiments revealed that all compounds were moderate to highly active against selected bacterial strains but inactive as antifungal except Pd(II) which showed a moderate antifungal activity. Gel electrophoresis showed insignificant nucleases activity for the ligand or its metal complexes even in the presence of H₂O₂ providing protection of DNA from damage. The antitumor activity of our compounds may be not due to DNA cleavage but may be referred to a mechanism similar to that of 5‐fluorouracil which interfere with DNA replication. The present work suggests the use of this ligand in the design and development of new anticancer drugs.     

Probing Cellular Binding of Dendrofullerene by in‐situ Electrochemical Contact Angle Measurement

Dendrofullerene (C₆₀DF) is a novel fullerene derivative with potential and promising biomedical applications. In this work, electrochemical/contact angle behavior of C₆₀DF in the cellular system has been explored by in‐situ electrochemical contact angle measurement. This measuring system is a newly developed technique which can provide electrochemical and contact angle detection simultaneously. The electrochemical results indicate that dendrofullerene may effectively bind and permeate the tumor cell membrane and then distribute into the cancer cells. Our observations of in‐situ electrochemical contact angle measurement also illustrate that the permeation and interaction of C₆₀DF with target cancer cells may lead to some variation of the configurational structure of the relative cell membrane and thus result in the change of hydrophilic/hydrophobic properties of target cellular system. Furthermore, through confocus fluorescence microscopy study we found that, upon application of C₆₀DF, the intracellular accumulation of anticancer drug daunorubicin in leukemia K562 cells could be remarkably enhanced by C₆₀DF. Therefore fullerene derivatives were demonstrated to be a good candidate that can play an important role in improving the intracellular drug uptake in the target cancer cells.     

Design,Synthesis, and Anticancer Activities of Benzofuran–Isatin Hybrids Tethered by Pentylene and Hexylene

Fourteen benzofuran–isatin hybrids 6a – f and 7a – h tethered via alkyl linker (pentylene and hexylene) were designed and synthesized, and hybrids 6c – f and 7a – h were screened for their in vitro anticancer activity against various human cancer cell lines. The majority of the hybrids were active against the tested cancer cells, and the most active hybrids 7g (half maximal inhibitory concentration/IC₅₀: 77.2–88.9 μM) and 7h (IC₅₀: 65.4–89.7 μM), which possessed broad spectrum anticancer activity were as potent as the reference vorinostat (IC₅₀: 64.2–>100 μM) against all tested cancer cell lines, could act as leads for further investigations. The structure–activity relationship is also discussed, and the enriched structure–activity relationship may afford useful information for further rational design of the candidates with higher activity.     

Histone‐Deacetylase‐Targeted Fluorescent Ruthenium(II) Polypyridyl Complexes as Potent Anticancer Agents

Histone deacetylases inhibitors (HDACis) have gained much attention as a new class of anticancer agents in recent years. Herein, we report a series of fluorescent ruthenium(II) complexes containing N¹‐hydroxy‐N⁸‐(1,10‐phenanthrolin‐5‐yl)octanediamide ( L ), a suberoylanilide hydroxamic acid (SAHA) derivative, as a ligand. As expected, these complexes show interesting chemiphysical properties, including relatively high quantum yields, large Stokes shifts, and long emission lifetimes. The in vitro inhibitory effect of the most effective drug, [Ru(DIP)₂ L ](PF₆)₂ ( 3 ; DIP: 4,7‐diphenyl‐1,10‐phenanthroline), on histone deacetylases (HDACs) is approximately equivalent in activity to that of SAHA, and treatment with complex 3 results in increased levels of the acetylated histone H3. Complex 3 is highly active against a panel of human cancer cell lines, whereas it shows relatively much lower toxicity to normal cells. Further mechanism studies show that complex 3 can elicit cell cycle arrest and induce apoptosis through mitochondria‐related pathways and the production of reactive oxygen species. These data suggest that these fluorescent ruthenium(II)–HDACi conjugates may represent a promising class of anticancer agents for potential dual imaging and therapeutic applications targeting HDACs.     

A Click Chemistry-Based Artificial Metallo-Nuclease

Artificial metallo-nucleases (AMNs) are promising DNA damaging drug candidates. Here, we demonstrate how the 1,2,3-triazole linker produced by the Cu-catalysed azide-alkyne cycloaddition (CuAAC) reaction can be directed to build Cu-binding AMN scaffolds. We selected biologically inert reaction partners tris(azidomethyl)mesitylene and ethynyl-thiophene to develop TC-Thio, a bioactive C₃-symmetric ligand in which three thiophene-triazole moieties are positioned around a central mesitylene core. The ligand was characterised by X-ray crystallography and forms multinuclear Cu^II and Cu^I complexes identified by mass spectrometry and rationalised by density functional theory (DFT). Upon Cu coordination, Cu^II-TC-Thio becomes a potent DNA binding and cleaving agent. Mechanistic studies reveal DNA recognition occurs exclusively at the minor groove with subsequent oxidative damage promoted through a superoxide- and peroxide-dependent pathway. Single molecule imaging of DNA isolated from peripheral blood mononuclear cells shows that the complex has comparable activity to the clinical drug temozolomide, causing DNA damage that is recognised by a combination of base excision repair (BER) enzymes.     

Synthesis,characterization and biological evaluation of a cobalt(II) complex with 5‐chloro‐8‐hydroxyquinoline as anticancer agent

A new cobalt(II) complex ( 1 ) of 5‐chloro‐8‐hydroxyquinoline was prepared and structurally characterized using infrared spectroscopy, electrospray ionization mass spectrometry, elemental analysis, single‐crystal X‐ray diffraction as well as powder X‐ray diffraction. Its biological activities including DNA binding and anticancer activity were investigated. The DNA binding study of complex 1 suggested that it interacted with calf thymus DNA mainly via an intercalative binding mode. The in vitro anticancer activity of complex 1 was screened against a series of tumor cell lines as well as the normal liver cell line HL‐7702 using MTT assay. complex 1 showed much higher cytotoxicity than corresponding metal salt and ligand towards the five tested tumor cell lines, in which T‐24 was the most sensitive tumor cell line towards 1, with IC₅₀ value of 7.04 ± 0.06 μM. complex 1 was found to greatly induce cell cycle arrest in T‐24 cells at S phase, and consequently to induce cell apoptosis in a dose‐dependent mode suggested by cell apoptosis analysis via Hoechst 33258 and acridine orange/ethidium bromide staining assays. The cell apoptosis mechanism of 1 was studied targeting the mitochondrion‐mediated pathway, since the apoptotic mechanism in the T‐24 cells treated by 1 was investigated by reactive oxygen species (ROS) detection, intracellular calcium concentration measurement and caspase‐9/3 activity assay. The results suggested that the cell apoptosis induced by 1 was closely related to the loss of mitochondrial membrane potential, ROS production and enhancement of intracellular [Ca²⁺], which would trigger the caspase‐9/3 activation via a mitochondrial dysfunction pathway. Copyright © 2016 John Wiley & Sons, Ltd.     

Abeliaside,a new phenolic glucoside from Abelia triflora

A new phenolic glucoside, abeliaside, along with four known compounds, 5,6,7,4′-tetrahydroxy flavones, caffeic acid, 4-O-caffeoylquinic acid and caffeic acid glucoside, was isolated from the leaves of Abelia triflora R. Br. (Caprifoliaceae). The structure of the new compound was elucidated by different spectroscopic techniques. Compounds 1–5 were assayed for their anticancer activities against two cancerous human cell lines, MCF-7 and PC-3 cells, and normal Vero cell line using the crystal violet staining method. From the results it could be seen that caffeic acid possessed the highest anticancer effect against MCF-7 (IC₅₀: 17 μg/mL) and PC-3 (IC₅₀: 20.1 μg/mL) compared to vinblastine sulphate as reference drug (IC₅₀: 4.6, 2.8 μg/mL). The other compounds showed weak anticancer activity on both cell lines.     

CO/light dual-activatable Ru(ii)-conjugated oligomer agent for lysosome-targeted multimodal cancer therapeutics

Stimuli-activatable and subcellular organelle-targeted agents with multimodal therapeutics are urgently desired for highly precise and effective cancer treatment. Herein, a CO/light dual-activatable Ru(ii)-oligo-(thiophene ethynylene) (Ru-OTE) for lysosome-targeted cancer therapy is reported. Ru-OTE is prepared via the coordination-driven self-assembly of a cationic conjugated oligomer (OTE-BN) ligand and a Ru(ii) center. Upon the dual-triggering of internal gaseous signaling molecular CO and external light, Ru-OTE undergoes ligand substitution and releases OTE-BN followed by dramatic fluorescence recovery, which could be used for monitoring drug delivery and imaging guided anticancer treatments. The released OTE-BN selectively accumulates in lysosomes, physically breaking their integrity. Then, the generated cytotoxic singlet oxygen (¹O₂) causes severe lysosome damage, thus leading to cancer cell death via photodynamic therapy (PDT). Meanwhile, the release of the Ru(ii) core also suppresses cancer cell growth as an anticancer metal drug. Its significant anticancer effect is realized via the multimodal therapeutics of physical disruption/PDT/chemotherapy. Importantly, Ru-OTE can be directly photo-activated using a two-photon laser (800 nm) for efficient drug release and near-infrared PDT. Furthermore, Ru-OTE with light irradiation inhibits tumor growth in an MDA-MB-231 breast tumor model with negligible side effects. This study demonstrates that the development of an activatable Ru(ii)-conjugated oligomer potential drug provides a new strategy for effective subcellular organelle-targeted multimodal cancer therapeutics.

The anticancer therapeutics of lysosome disruption/PDT/chemotherapy based on Ru-OTE complex was achieved, which provides a new strategy for developing multimodal and effective stimuli-activatable subcellular organelle-targeted cancer therapeutics.     

In silico model for P-glycoprotein substrate prediction: insights from molecular dynamics and in vitro studies

P-glycoprotein (P-gp) is a plasma membrane efflux transporter belonging to ATP-binding cassette superfamily, responsible for multidrug resistance in tumor cells. Over-expression of P-gp in cancer cells limits the efficacy of many anticancer drugs. A clear understanding of P-gp substrate binding will be advantageous in early drug discovery process. However, substrate poly-specificity of P-gp is a limiting factor in rational drug design. In this investigation, we report a dynamic trans-membrane model of P-gp that accurately identified the substrate binding residues of known anticancer agents. The study included homology modeling of human P-gp based on the crystal structure of C. elegans P-gp, molecular docking, molecular dynamics analyses and binding free energy calculations. The model was further utilized to speculate substrate propensity of in-house anticancer compounds. The model demonstrated promising results with one anticancer compound (NSC745689). As per our observations, the molecule could be a potential lead for anticancer agents devoid of P-gp mediated multiple drug resistance. The in silico results were further validated experimentally using Caco-2 cell lines studies, where NSC745689 exhibited poor permeability (P _app 1.03 ± 0.16 × 10^?6 cm/s) and low efflux ratio of 0.26.     

<Superscript>99m</Superscript>Tc(CO)<Subscript>3</Subscript>–AOPA colchicine conjugate as a potential tumor imaging agent

This work reports the synthesis, radiolabeling and preliminary biodistribution results in tumor-bearing mice of the ^99mTc(CO)₃–AOPA colchicine conjugate. The novel ligand was successfully synthesized by conjugation of N-(acetyloxy)-2-picolylamino (AOPA) to deacetylcolchicine via a short carbonyl-methylene linker. Radiolabeling was performed in high yield with [^99mTc(CO)₃]⁺ core. ^99mTc(CO)₃–AOPA colchicine conjugate was hydrophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that ^99mTc(CO)₃–AOPA colchicine conjugate accumulated in the tumor with good uptake and retention. However, its clearance from normal organs was not so fast, resulting in poor T/NT ratios. Further modification on the linker or/and ^99mTc-chelate to improve the tumor targeting efficacy and in vivo kinetic profiles is currently in progress.     

Elaborated spectral,modeling, QSAR,docking, thermal,antimicrobial and anticancer activity studies for new nanosized metal ion complexes derived from sulfamerazine azodye

New azodye ligand (H₂L) and its relative Cr(III)-, Mn(II)-, Fe(III)-, Co(II)-, Ni(II)-, Cu(II)-, Zn(II)- and Cd(II)-nanosized complexes were prepared. A new synthesized compounds were characterized using spectral (mass, IR, UV–Vis, XRD, and ESR) and analytical (elemental, molar conductance, thermal and magnetic moment measurements) tools. Infrared spectra showed that the ligand behaves as a monobasic bidentate, coordinating with central atoms through carbonyl oxygen and α-hydroxyl group. The geometrical structures of Cr(III) and Fe(III) complexes were found to be in octahedral configuration, whereas Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes have tetrahedral forms. XRD patterns reflect an amorphous appearance of all investigated complexes. TEM images showed nanosized particles and identical distribution over the complex surface. Molecular modeling for the drug ligand and its metal ion complexes were performed using Gaussian09 program to assert on their structural formulae. Some essential parameters were extracted using HOMO and LUMO energies. AutoDock tools 4.2 was used to simulate the interaction process with infected cell proteins to expect the experimental pathway. The inhibition activity of drug ligand and its metal ion complexes was evaluated towards different types of bacteria and fungi through in vitro antimicrobial activities. The antitumor activities of all compounds are straightened towards human liver carcinoma (HEPG2) cell lines. Fe(III) and Co(II) complexes exhibited IC₅₀ of 2.90 and 4.23 µg mL^?1, respectively, which means they are more potent anticancer drug than the standard (doxorubicin, IC₅₀ = 4.73 µg mL^?1). Therefore, the two complexes may consider promising anticancer drugs.

     

Transition metal complexes of α-aminophosphonates part II: Synthesis,spectroscopic characterization,and in vitro anticancer activity of copper(II) complexes of α-aminophosphonates

Abstract

A one pot procedure was used to synthesize two new derivatives of α-aminophosphonates. Novel copper(II) complexes of α-aminophosphonates were synthesized by coordinating different copper salts with the newly synthesized α-aminophosphonates. Their structures were characterized by different spectral and analytical techniques. Evaluation of the metal-free ligands HL1, HL², and their Cu(II) complexes against human colon carcinoma HT-29 cell lines was performed, using cisplatin as a reference drug. The results indicated that the complexes of the ligand HL¹ exhibited enhanced anticancer activity, while ligand HL² complexes showed decreased anticancer activity.