Cyclometalated Ruthenium(II) Anthraquinone Complexes Exhibit Strong Anticancer Activity in Hypoxic Tumor Cells

Hypoxia is the critical feature of the tumor microenvironment that is known to lead to resistance to many chemotherapeutic drugs. Six novel ruthenium(II) anthraquinone complexes were designed and synthesized; they exhibit similar or superior cytotoxicity compared to cisplatin in hypoxic HeLa, A549, and multidrug‐resistant (A549R) tumor cell lines. Their anticancer activities are related to their lipophilicity and cellular uptake; therefore, these physicochemical properties of the complexes can be changed by modifying the ligands to obtain better anticancer candidates. Complex 1 , the most potent member of the series, is highly active against hypoxic HeLa cancer cells (IC₅₀=0.53 μM ). This complex likely has 46‐fold better activity than cisplatin (IC₅₀=24.62 μM ) in HeLa cells. This complex tends to accumulate in the mitochondria and the nucleus of hypoxic HeLa cells. Further mechanistic studies show that complex 1 induced cell apoptosis during hypoxia through multiple pathways, including those of DNA damage, mitochondrial dysfunction, and the inhibition of DNA replication and HIF‐1α expression, making it an outstanding candidate for further in vivo studies.     

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.     

Synthesis,DNA-binding,and antitumor activity of polypyridyl-ruthenium(II) complexes [Ru(L)2(DClPIP)] (L = bpy,phen; DClPIP = 2-(2,4-dichlorophenyl)-1H-imidazo[4,5-f][1, 10]phenanthroline)

Abstract

Two new ruthenium(II) complexes, [Ru(bpy)₂(DClPIP)](ClO₄)₂ (1) and [Ru(phen)₂(DClPIP)](ClO₄)₂ (2) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, and DClPIP = 2-(2,4-dichlorophenyl)-1H-imidazo[4,5-f][1, 10]phenanthroline), have been prepared in high yield by using microwave-assisted synthesis technology. The anticancer activity of the two ruthenium(II) complexes against A549, C6, CNE-1 and MDA-MB-231 cell lines has been evaluated by MTT assay and results showed that 2 exhibited higher antitumor activity than 1 toward all the selected tumor cell lines. Besides, A549 cell line was sensitive to both ruthenium(II) complexes, especially to 2 (IC₅₀ = 8.01?±?0.36?μM). Meanwhile, 2 showed low toxicity against MCF-10A human normal cells. Furthermore, the DNA-binding properties of the two new ruthenium(II) complexes with CT-DNA have been investigated by electronic absorption titration, luminescence spectra, circular dichroism spectra and viscosity measurements. The results suggested that 1 and 2 were able to interact with CT-DNA via intercalative mode with a strong binding affinity in the order 2?>?1. All of these results suggested that anticancer activity of both ruthenium(II) complexes could be closely related to their interaction with DNA.     

DNA binding,crystal structure,molecular docking studies and anticancer activity evaluation of a copper(II) complex

A copper complex [Cu(HPBM)(l-Phe)(H₂O)]·ClO₄ (1) (HPBM = 5-methyl-2-(2′-pyridyl)benzimidazole, l-Phe = l-phenylalanine anion) was synthesized and characterized by elemental analysis, IR, ESI–MS, HR–ESI–MS, ESR spectroscopy, and by X-ray single-crystal analysis. The binding constant of the complex with calf thymus DNA (CT-DNA) was determined as 7.38 (± 0.57) × 10⁴ M^?1. Further studies indicated that the complex interacts with CT-DNA through minor groove binding. The in vitro cytotoxic activities of both the free proligand and the complex against Eca-109, HeLa and A549 cancer cells and normal LO2 cells were evaluated by the MTT method. The IC₅₀ values range from 5.7 ± 0.1 to 8.3 ± 0.6 µM. Free HPBM displays no cytotoxic activity against the selected cancer cells, with IC₅₀ values more than 100 µM. Double staining analysis showed that the complex can induce apoptosis in Eca-109 cells. Comet assays demonstrated that the complex can damage DNA and cause apoptosis. The complex also induces an increase in intracellular reactive oxygen species and a reduction in mitochondrial membrane potential. The complex can also increase the intracellular Ca²⁺ level and induce release of cytochrome c. The cell cycle arrest was investigated by flow cytometry. The results demonstrate that the complex induces apoptosis in Eca-109 cells through DNA-binding and ROS-mediated mitochondrial dysfunctional pathways.     

Synthesis,Structural, Biological Evaluation,Molecular Docking and DFT Studies of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) Complexes bearing Heterocyclic Thiosemicarbazone ligand

A new ligand, 2‐aminonicotinaldehyde N‐methyl thiosemicarbazone (ANMTSC) and its metal complexes [Co(II) ( 1 ); Ni(II) ( 2 ); Cu(II) ( 3 ); Zn(II) ( 4 ); Cd(II) ( 5 ) or Hg(II) ( 6 )] were synthesized. The compounds were characterized by analytical methods and various spectroscopic (infrared, magnetic, thermal, ¹H, ¹³C NMR, electronic and ESR) tools. The structure of ANMTSC ligand was confirmed by single crystal X‐ray diffraction study. The spectral data of metal complexes indicate that the ligand acts as mononegative, bidentate coordination through imine nitrogen (N) and thiocarbonyl sulphur (S^?) atoms. The proposed geometries for complexes were octahedral ( 1 – 2 ), distorted octahedral ( 3 ) and tetrahedral ( 4 – 6 ). Computational details of theoretical calculations (DFT) of complexes have been discussed. The compounds were subjected to antimicrobial, antioxidant, antidiabetic, anticancer, ROS, studies and EGFR targeting molecular docking analysis. Complex 5 has shown excellent antibacterial activity and the complexes 2 and 5 have shown good antifungal activity. The complexes 1 and 4 displayed good antioxidant property with IC₅₀ values of 11.17 ± 1.92 μM and 10.79 ± 1.85 μM, respectively compared to standard. In addition, in vitro anticancer activity of the compounds was investigated against HeLa, MCF‐7, A549, IMR‐32 and HEK 293 cell lines. Among all the compounds, complex 4 was more effective against HeLa (IC₅₀ = 10.28 ± 0.69 μM), MCF‐7 (IC₅₀ = 9.80 ± 0.83 μM), A549 (IC₅₀ = 11.08 ± 0.57 μM) and IMR‐32 (10.41 ± 0.60 μM) exhibited superior anticancer activity [IC₅₀ = 9.80 ± 0.83 ( 4 ) and 9.91 ± 0.37 μM ( 1 )] against MCF‐7 compared with other complexes.     

Synthesis,characterization, and antitumor activity of mononuclear and dinuclear ruthenium complexes

Abstract

Dinuclear ruthenium complexes [Ru₂(bpy)₄BL](ClO₄)₂ (Ru-1), where bpy = 2,2′-bipyridine and BL = 2,2′-((1E,1′E)-((E)-diazene-1,2-diyl-bis(2,1-phenylene))-bis(azanylylidene))bis(methanylylidene))diphenol (a bidentate bridging ligand), and mononuclear ruthenium complexes [Ru(bpy)₂L](ClO₄) (Ru-2), where L = (E)-2-((phenylimino)methyl)phenol, were synthesized and characterized by elemental analysis and electrospray ionization mass spectrometry. Their photophysical and electrochemical properties were also studied. The cytotoxicity of the two complexes in vitro was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results indicated that Ru-1 and Ru-2 exhibited significant dose-dependent cytotoxicity to human breast cancer (MCF-7), gastric cancer (SGC-7901), cervical cancer (Hela), and lung cancer (A549) tumor cell lines. Ru-1 showed excellent antitumor effects in a cellular study (IC₅₀ values of 3.61 μM for MCF-7 human breast cancer cells in vitro). However, Ru-2 exhibited the highest cytotoxicity to Hela cells; the IC₅₀ value is 3.71 μM. The results reveal that Ru-1 and Ru-2 have obvious selectivity and might be a potential anticancer agent that could improve the efficacy of common anticancer therapies.     

Topoisomerase I inhibitory and photocleavage activity of non‐dppz DNA ‘light switches’ based on ruthenium complexes containing nitro group

A new polypyridyl ligand containing a nitro group and two new ruthenium complexes of it were synthesized. The two complexes exhibited non‐dppz DNA ‘light switch’ effects after interaction with calf thymus DNA. Introducing both electron‐withdrawing group (─ NO₂) and electron‐donating group (─ CH₃) may be the reason that the two complexes display DNA ‘light switch’ behaviors. Furthermore, one of the complexes showed higher photocleavage activity, topoisomerase I inhibition activity and DNA affinity than the other. The present work shows that the more active complex can be employed as a non‐dppz DNA ‘light switch’, DNA photocleaver and topoisomerase I inhibitor. In addition, the two complexes have no or weak cytotoxic activities against Eca‐109 and A549 cells.     

Synthesis and anticancer activity of benzotriazole derivatives

A series of benzotriazole (BTA) derivatives were synthesized as tyrosine protein kinase inhibitors using fragment-based design strategy. All desired compounds were synthesized with the reaction of benzotriazole, chloroacetonitrile and aromatic aldehyde using Ultrasonic-Microwave method and characterized by IR, ¹H and ¹³C-NMR, mass spectrometry (MS) and elemental analysis. The anticancer activity of these compounds was evaluated by CCK-8 method against carcinoma VX2, lung cancer A549, stomach cancer cell lines MKN45 and MGC in vitro. The results showed that all compounds showed good antiproliferative activity. In particular, compound 2.1 showed the most prominent inhibition of VX2 cell lines with IC₅₀ of 3.80 ± 0.75 μM. Compound 2.2 exhibited highly potent anticancer activity of stomach MGC cell lines with IC₅₀ of 3.72 ± 0.11 μM. A549 and MKN45 cell lines were sensitive to compound 2.5 with IC₅₀ of 5.47 ± 1.11 and 3.04 ± 0.02 μM, respectively.     

Synthesis,biological evaluation and molecular docking studies of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives

A series of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives 3(a-u) were designed and synthesized via selective amidation of methyl-2-(2-cyanophenyl)acetates over amidine formation by using AlMe₃ as catalyst in good yields. All the newly synthesized derivatives were well characterized by ¹H NMR, ¹³C NMR, FTIR and HRMS spectral techniques. All the synthesized title compounds were evaluated for their in vitro anticancer activity against three cancer cell lines. Among all compounds, 3i (IC₅₀?=?1.20 μM, IC₅₀?=?1.10 μM), 3j (IC₅₀?=?0.11 μM, IC₅₀?=?0.18 μM), 3o (IC₅₀?=?0.98 μM, IC₅₀?=?2.76 μM) showed excellent inhibitory activity than the standard Etoposide (IC₅₀?=?2.11 μM, IC₅₀?=?3.08 μM) against MCF-7 and A-549 cell lines, respectively. Docking analysis of all the compounds with the human topoisomerase II revealed that the compound 3j fitted well in the active site pocket, showing the best docking score of 158.072 kcal/mol.

     

Design,synthesis, anticancer activity,and in silico studies of novel imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives

A novel series of imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives were designed, synthesized, and evaluated for their anticancer activity against two different human cancer cell lines. Most of the synthesized compounds displayed anticancer activity with IC₅₀ values from 2.35 to 120.46 μM. Furthermore, compounds 9b , 9c, 9d, 9f , and 9j showed potent inhibitory activity against cancer cell lines, with IC₅₀ values close to that of standard drug. It is important to note that compound 9d was more potent than the standard drug cisplatin with IC₅₀ values of 10.89 and 2.35 μM against Hela cell line and MCF-7 cell line, respectively.     

Synthesis,characterization, cytotoxicity and computational studies of new phosphine‐ and carbodithioate‐based palladium(II) complexes

In quest of new metallo‐pharmaceuticals with enhanced anticancer activity, four new phosphine‐ and carbodithioate‐based Pd(II) complexes of the type [(R)CS₂Pd(PR₃)Cl] (where R = 4‐(2‐hydroxyethyl)piperazine ( 1 , 2 ), dibenzyl ( 3 , 4 ); PR₃ = diphenyl(p ‐tolyl)phosphine ( 1 , 3 ), tris(4‐tolyl)phosphine ( 2 , 4 )) were synthesized and characterized using elemental analysis, Fourier transform infrared and NMR (¹H, ¹³C and ³¹P) spectroscopies and single‐crystal X‐ray diffraction. The X‐ray diffraction data confirmed the pseudo square‐planar geometry ensuring bidentate coordination mode of carbodithioate ligands. Anticancer activity of the synthesized complexes and their ligands was assessed against human lung (A549), breast (MCF‐7) and prostate (PC3) carcinoma cells using MTT assay. All the tested compounds showed activity in micromolar range. In many cases, the cytotoxicity of the synthesized complexes was higher than or comparable to that of the standard drugs cisplatin and doxorubicin. Complex 3 emerged as the most promising compound with the lowest IC₅₀ values of 4.83, 3.72 and 5.11 μM for A549, MCF‐7 and PC3 carcinoma cell lines, respectively. DNA binding studies were also carried out using UV–visible spectroscopy. We extended our investigations to explore the mechanism of anticancer activity using in silico tools. Based on the mechanism of action of standard drugs used, extensive docking studies were carried out on the three different biomolecular targets.     

Synthesis,characterization and in vitro biological activities of ruthenium(II) polypyridyl complexes

The ruthenium(II) polypyridyl complexes [Ru(dmb)₂(TCPI)](PF₆)₂ (1) and [Ru(ttbpy)₂(TCPI)](PF₆)₂ (2) (dmb = 4,4′-dimethyl-2,2′-bipyridine, TCPI = 2-(3-(1H-1,3,7,8-tetraazacyclopenta[l]phenanthren-2-yl)phenyl)benzo[de]isoquinoline-1,3-dione, ttbpy = 4,4′-ditertiary butyl-2,2′-bipyridine) were synthesized and characterized. The in vitro cytotoxicities of the complexes were examined against a panel of cancer cell lines including SGC-7901, PC-12, HepG-2, SiHa, Eca-109, HeLa, Eca-9706, HOS and LO₂ by 3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide (MTT) method. Both complexes show higher activities against PC-12 cells, with IC₅₀ values of 34.4 ± 1.3 and 26.8 ± 2.4 μM for 1 and 2, respectively. Cell apoptosis was assayed with acridine orange (AO) and ethidium bromide (EB) and annexin V/PI staining methods using fluorescence microscopy and flow cytometry. The reactive oxygen species, mitochondrial membrane potential and cell cycle distribution were assessed. Cell invasion was determined by Matrigel invasion assay, and the proteins associated with cell apoptosis were analyzed by western blot. The results suggest that the complexes induce the apoptosis of PC-12 cells through a ROS-mediated mitochondrial dysfunction pathway, accompanied by regulation of the expression of caspases and Bcl-2 family proteins.     

Semisynthetic derivatives of haemanthamine and their in vitro antiproliferative activity evaluation against a panel of human cell lines

In this study, a new series of aliphatic, cyclic, and heterocyclic derivatives of haemanthamine was designed and synthesized to enhance its inhibitory effect on the proliferation and viability of cancer cells. A library of haemanthamine derivatives was subjected to 10 μM single-dose cytotoxicity screening against a panel of human cell lines of various histotypes. Initial cytotoxicity evaluation of the parent haemanthamine (1) and a series of twenty-nine (2–30) semisynthetic analogues showed that for some of the newly formed derivatives, a certain cytotoxic effect was observed, in one case even higher than that of the parent compound. Specifically, 11-O-(4-chloro-3-nitrobenzoyl)haemanthamine (21) showed an enhanced antiproliferative effect, where the mean growth percent (GP) value was 5% compared to haemanthamine, leading to a decrease in the GP to 25%. Among ten cell lines tested, derivative 21, bearing a substituted aromatic ester bond via C-11 of haemanthamine, had excellent activity for inhibiting the growth of HeLa (IC₅₀ = 0.2 ± 0.1 μM), A549 (IC₅₀ = 1.7 ± 0.1 μM) and HT-29 (IC₅₀ = 2.2 ± 0.1 μM) cells. When evaluating response kinetics, we found that 21 and haemanthamine dose- and time-dependently suppressed the proliferation of A549 cells. In contrast to haemanthamine (1), Trypan blue and lactate dehydrogenase (LDH) release assay revealed that 21 was capable of reducing the survival of A549 cells.     

Influence of Halogen Substitution in the Ligand Sphere on the Antitumor and Antibacterial Activity of Half‐sandwich Ruthenium(II) Complexes [RuX(η6‐arene)(C5H4N‐2‐CH=N‐Ar)]+

New complexes [(η⁶‐p‐cymene)Ru(C₅H₄N‐2‐CH=N–Ar)X]PF₆ [X = Br ( 1 ), I ( 2 ); Ar = 4‐fluorophenyl ( a ), 4‐chlorophenyl ( b ), 4‐bromophenyl ( c ), 4‐iodophenyl ( d ), 2,5‐dichlorophenyl ( e )] were prepared, as well as 3a – 3e (X = Cl) and the new complexes [(η⁶‐arene)RuCl(N‐N)]PF₆ (arene = C₆H₅OCH₂CH₂OH, N‐N = 2,2′‐bipyridine ( 4 ), 2,6‐(dimethylphenyl)‐pyridin‐2‐yl‐methylene amine ( 5 ), 2,6‐(diisopropylphenyl)‐pyridin‐2‐yl‐methylene amine ( 6 ); arene = p‐cymene, N‐N = 4‐(aminophenyl)‐pyridin‐2‐yl‐methylene amine ( 7 )]. X‐ray diffraction studies were performed for 1a , 1b , 1c , 1d , 2b , 5 , and 7 . Cytotoxicities of 1a – 1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco‐2) (IC₅₀: 35.8–631.0 μM), breast adenocarcinoma (MCF7) (IC₅₀: 36.3–128.8.0 μM), and hepatocellular carcinoma (HepG2) (IC₅₀: 60.6–439.8 μM), 3a – 3e were tested against HepG2 and Caco‐2, and 4 – 7 were tested against Caco‐2. 1 – 7 were tested against non‐cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5‐fluorouracil (5‐FU), but 3a – 3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC₅₀ than 5‐FU. Complexes with X = Br or I had moderate activity against Caco‐2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a , 2b , 3a , and 7 were tested against antibacterial susceptible and resistant Gram‐negative and ‐positive bacteria. 1a , 2b , and 3a showed activity against methicillin‐resistant S. aureus (MIC = 31–2000 μg · mL^–1).     

New metal complexes of sulfonamide: Synthesis,characterization, in‐vitro anticancer,anticholinesterase, antioxidant,and antibacterial studies

In this research work a sulfonamide from tranexamic acid has been synthesized followed by its metal complexation. p‐Bromo benzene sulfonyl chloride was used to synthesize sulfonamide using eco‐friendly atmosphere. The sulfonamide prepared from tranexamic acid has been utilized for the preparation of metal complexes with various metals like Ni, Cu, Co, Mn, Pb, Cd, Cr, Fe, Sn, and Sr. All synthesized compounds were characterized by applying different spectral techniques such as Fourier‐transform infrared (FTIR), mass spectrometry, and X‐ray diffraction (XRD) analysis. The biological activities such as radical scavenging activity, enzyme inhibition, antifungal, antibacterial, and anticancer were performed. It was concluded from the results that compounds showed moderate to good activity. Cu complex of sulfonamide showed the highest antioxidant potential (87.69 ± 1.8% with IC₅₀ 137 ± 1.0 μg) while Cr complex depicted the highest activity against both enzymes; AChE (73.51 ± 1.7% with IC₅₀ 165 ± 1.1 μg) and BChE (70.05 ± 1.3% with IC₅₀ 152 ± 1.8 μg). Mn complex showed good results against six bacterial strains comparable with standard drug. Cr complex depicted highest anticancer activity against MCF7 and human corneal epithelial cell (HCEC) cell lines 45.73% and 25.40%, respectively. These results concluded that metal complexes of sulfonamide may be good induction in the future for medical purposes.     

Synthesis,structure, characterization and biological evaluation of 3‐substituted 1‐pyridin‐2‐ylimidazo[1,5‐a]pyridine‐based copper(I)–phosphine complexes for anticancer drug screening

Copper(I) complexes of the types [Cu(N–N)(PPh₃)₂]NO₃ (LC41–LC44) and [Cu(N–N)(PPh₃)(NO₃)] (LC45) carrying 3‐substituted 1‐pyridine‐2‐ylimidazo[1,5‐a]pyridine (N–N) derivatives and triphenylphosphine (PPh₃) ligands have been prepared. The synthesized copper(I)–phosphine complexes were fully characterized by NMR, IR, ESI‐MS and UV–visible spectroscopy as well as by cyclic voltammetry. Selected structures such as LC42, LC43 and LC45 were additionally analysed by single‐crystal X‐ray method, which show that copper(I) centre adopts a highly distorted tetrahedral geometry. The ¹H and ¹³C NMR spectral data of the complexes throw light on the nature of metal–ligand bonding. They display dπ–π* metal‐to‐ligand charge transfer (MLCT) transition and show quasireversible Cu^I/Cu^II metal oxidation. Among the copper(I)–phosphine complexes, LC41–LC44 exhibit moderate cytotoxicity (IC₅₀: 24 h, 67–74 μM; 48 h, 58–70 μM) against human lung epithelial adenocarcinoma A549 cells, whereas LC45 displays the best activity (IC₅₀: 24 h, 42 μM; 48 h, 34 μM) for A549 cancer cell line, which is better than that of the commercial antitumor drug cisplatin. All the complexes also displayed excellent selectivity by being relatively inactive against the human lung epithelial L132 normal cell line with selectivity index (SI) values ranging from 3.4 to 7.4. The complexes block cell cycle progression of A549 cells in G₀/G₁ phase. FACSVerse analyses are suggestive of reactive oxygen species (ROS) generation and apoptotic cell death induced by the LC41, LC43 and LC45. The induction of apoptosis in A549 cells was shown by Annexin V with propidium iodide (PI) and 4′,6‐diamidino‐2‐phenylindole (DAPI) staining methods and established the ability of LC41, LC43 and LC45 to accumulate in the cell nuclei.     

Design,synthesis, and antilung adenocarcinoma activity research of novel paeonol Schiff base derivatives containing a 1,2,3-triazole moiety

A new series of paeonol Schiff base derivatives containing a 1,2,3-triazole moiety were synthesized using the copper(I) catalyzed azide-alkynecycloaddition (CuAAC) reaction and evaluated for their cytotoxicity in vitro against human cervical carcinoma HeLa cells, human lung cancer A549 cells, and human liver cancer HepG2 cells. Unfortunately, all the tested compounds showed poor activities toward the human cervical carcinoma HeLa cells and human liver cancer HepG2 cells. However, compounds (E)-2-(1-(((1-[2-fluorophenyl]-1H-1,2,3-triazol-4-yl)methyl)imino)ethyl)-5-methoxyphenol ( 4c ) and (E)-2-(1-(((1-[3- chlorophenyl]-1H-1,2,3-triazol-4-yl)methyl)imino)ethyl)-5-methoxyphenol ( 4i ) exhibited inhibitory activities toward human lung cancer A549 cells (IC₅₀ = 45.1 μM for 4c and 78.9 μM for 4i ) compared with that of paeonol, which indicated that such paeonol Schiff base derivatives containing a 1,2,3-triazole moiety could be further modified to obtain good cytotoxicity in vitro against human lung cancer A549 cells.     

Cyclometalated Palladium(II) N‐Heterocyclic Carbene Complexes: Anticancer Agents for Potent In Vitro Cytotoxicity and In Vivo Tumor Growth Suppression

Palladium(II) complexes are generally reactive toward substitution/reduction, and their biological applications are seldom explored. A new series of palladium(II) N‐heterocyclic carbene (NHC) complexes that are stable in the presence of biological thiols are reported. A representative complex, [Pd(C^N^N)(N,N′‐nBu₂NHC)](CF₃SO₃) ( Pd1 d , HC^N^N=6‐phenyl‐2,2′‐bipyridine, N,N′‐nBu₂NHC=N,N′‐di‐n‐butylimidazolylidene), displays potent killing activity toward cancer cell lines (IC₅₀=0.09–0.5 μm ) but is less cytotoxic toward a normal human fibroblast cell line (CCD‐19Lu, IC₅₀=11.8 μm ). In vivo anticancer studies revealed that Pd1 d significantly inhibited tumor growth in a nude mice model. Proteomics data and in vitro biochemical assays reveal that Pd1 d exerts anticancer effects, including inhibition of an epidermal growth factor receptor pathway, induction of mitochondrial dysfunction, and antiangiogenic activity to endothelial cells.     

Preparation,characterization and biological evaluation of two chiral binuclear copper(II) complexes

Two chiral Cu(II) complexes of [Cu₂(R‐L)₂](PF₆)₂·2C₂H₅OH ( 1 ) and [Cu₂(S‐L)₂](PF₆)₂·2C₂H₅OH ( 2 ) (HL = 2‐(Bis(quinolin‐2‐ylmethyl)amino)‐1‐propanol) were designed and synthesized to serve as chemical nucleases and anticancer drugs. X‐ray crystallography revealed that two complexes contain chiral binuclear cations and PF₆^? anions. The interaction of two complexes with CT‐DNA was researched via various spectroscopic techniques and viscosity measurement, indicating that the complexes were bound to CT‐DNA by a classical intercalation binding mode. In addition, the two complexes exhibited remarkable DNA cleavage activity with an optimal dosage of 10 μM in the absence of any exogenous oxidant agent. Both of the complexes showed excellent in vitro cytotoxicity on A549 cell lines with IC₅₀ values in the low micromolar range. Moreover, complex 2 could damage DNA of A549 cells into fragmentation and then induced cell apoptosis in a dose‐dependent manner, which was demonstrated by comet assay and Hoechst 33342 staining experiment. Further research showed that complex 2 could also induce G₂ and S phase cell cycle arrest.     

Design,synthesis, and evaluation of novel combretastatin A-4 based chalcone derivatives as anticancer agents

A series of combretastatin A-4 based chalcones ( 14a-l ) were designed, synthesized and these compounds examined for inhibitory effects on the proliferation of human lung (A549), breast (MCF-7), melanoma (A375), and colon (HT-29) carcinoma cells. Compounds 14b , 14c , 14e , 14h , and 14i (tri/dimethoxy, methyl, and mono/dinitro derivatives) have exhibited the most potent antiproliferative activity with IC₅₀ < 2 μM and the hexa methoxy derivative 14b , the most promising one, which displayed the potent inhibitory activities in MCF-7 (IC₅₀: 10 nM), A375 (IC₅₀: 12 nM), and A549 (IC₅₀: 65 nM) cell lines, and is 18 times more potent than the CA-4. Compound 14b represents a new scaffold and the results provide insights into further development of anticancer agents.