Cervix Epitheloid Carcinoma Research Articles

Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers

In the present study, the various 28 hybrid molecules containing hydrazone and sulfonate moieties were synthesized and characterized by FTIR, 1H-NMR, 13C-NMR spectroscopy and LC-MS spectrometry, besides elemental analysis. The compounds were evaluated for their antiproliferative effects against six cancer cell lines, namely A549 (non-small cell lung cancer), MCF-7 (breast cancer), HT-29 (colorectal adenocarcinoma cancer), PC-3 (androgen-independent prostate adenocarcinoma), Hep3B (hepatocellular carcinoma cancer), and HeLa (epitheloid cervix carcinoma cancer). Among all the target compounds, compounds 4g and 4h exhibited more promising effects on MCF-7 cell lines (IC50 = 17.8 μM and 21.2 μM, respectively) with high selectivity. Further mechanistic studies proposed that compounds 4g and 4h induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating caspase-9 and caspase-3. The results have been encouraging enough to merit further investigation.

The effects of zinc(II)phthalocyanine photosensitizers on biological activities of epitheloid cervix carcinoma cells and precise determination of absorbed fluence at a specific wavelength

Photodynamic therapy (PDT) is an alternative way to treat the cancer non-surgically with minimum harm, in which a specific light and light sensitive photosensitizer (PS) is used. This study deals with the utilization of zinc photosensitizers (λmax ∼700 nm) from the group of phthalocyanines in photodynamic therapy. The photosensitizers differed in bearing either tetra- or octa-mercaptopropionic acid groups. The phthalocyanines (L1ZnPc and DipZnPc) were tested in cancer cell line, HeLa cell (epitheloid cervix carcinoma), by dark and light cytotoxicity. The photophysico-chemical properties of the resulting zinc photosensitizers were analyzed and to investigate the singlet oxygen's efficiency, photochemical properties were determined. For L1ZnPc, the singlet oxygen quantum yield was ΦΔ = 0.41 and for DipZnPc, the value was ΦΔ = 0.27. In addition to the experimental outcomes, this study handles detailed calculations of the absorbed light dose by the photosensitizer at a specific wavelength. In the light of this study, the researchers could get the insight of the precise amount of energy delivered to the cells by a laser beam for critical applications. The absorbed dose of the laser irradiation was calculated within a true wavelength range that is the most detailed explanation in literature.

Evaluation of Antiproliferative Palladium(II) Complexes of Synthetic Bisdemethoxycurcumin towards In Vitro Cytotoxicity and Molecular Docking on DNA Sequence.

Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal–ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities.

In vitro evaluation of immunobiological activity of simple mannolipids

Immunomodulation, cytotoxicity and anti-cancer activity of selected amphiphilic non-ionic (thio)alkyl α-D-mannosides (with aglycone of C6-C12) were investigated in vitro in human cervix epitheloid carcinoma cell line HeLa, murine melanoma cancer cells B16, murine lymphocytic leukemia cell line L1210, murine fibroblast cell line NIH 3 T3 and murine macrophage cell line RAW 264.7. Toxicological studies revealed structure-dependent immunobiological effectivity based on a tight interaction with relevant cells. The results demonstrated diverse immunomodulation of macrophage cell-line RAW264.7 proliferation and production of Th1 and Th2 cytokines, and induction of pro-inflammatory interleukins IL-1α, TNFα, IL-6, IL-12 and IL-17 and anti-inflammatory IL-10 following (thio)alkyl α-D-mannosides 24 and 48 h exposure. Direct application of alkyl mannosides MOC10 and MOC12 and their thio analogues MSC10 and MSC12 in reconstructed human EpiDerm™ and MOC12 and MSC12 in EpiOcular™ model assays for dermal and ocular irritation together with quantification of human proinflammatory cytokines IL-1α, TNFα, IL-6 and IL-8 culture media release was used to ascertain toxicological safety.

Cytoprotective Activity of Neichitti (Vernonia cinerea) in Human Embryonic Kidney (HEK293) Normal Cells and Human Cervix Epitheloid Carcinoma (HeLa) Cells against Cisplatin Induced Toxicity: A Comparative Study

Introduction: Traditional Siddha Medicine literatures suggest to use the decoction of Vernonia cinerea (VC) to alleviate toxic effects caused by metals. Cisplatin, a metal used in cancer treatment is known to cause nephrotoxicity.Aim: To evaluate and compare protective activity of aqueous extract and fractions of VC in Human Embryonic Kidney (HEK293) cells and Human Cervix Epitheloid Carcinoma (HELA) cell lines against cisplatin induced cytotoxicity.Materials and Methods: The Crude Aqueous Extract (CAE) was obtained from whole plant of VC. CAE was fractioned using nonpolar to polar solvents, and Butanol Fraction (BF) as well as Aqueous Fractions (AF) were obtained. The cell lines were exposed with the IC50 dose of cisplatin, then treated with different doses of the extract or fractions. After 48 hours of incubation, viable cell growth was determined by MTT reduction assay in all the treatments by observing at absorbance of 540 nm. Dose response (% cell viability) curve was drawn and the values were statistically compared using One-Way ANOVA, followed by Dunnett’s (2-sided) post-hoc test.Results: Aqueous fraction showed 2.8 times higher cytoprotection (improvement in cell viability by 54%) than CAE against cisplatin induced toxicity in HEK293 cells. BF did not show protective activity in HEK293 cells. In HELA cells, AF showed 1.73 times higher cytoprotection than CAE and 1.55 times higher cytoprotection than BF against cisplatin, as evidenced by improvement in cell viability by 30%, 11% and 13% in AF, CAE and BF respectively. AF exhibited 80% higher cytoprotection against cisplatin cytotoxicity in normal HEK293 than cancer HELA cells. Whereas, CAE and BF showed lesser cytoprotective activity than AF.Conclusion: This study created scientific basis for using Vernonia cinerea against metal toxicities in Siddha system and suggests that the AF is suitable for further discovery of drug that selectively protect normal renal cell during cisplatin treatment in cancer patients.

Concomitant reduction of dimethylformamide and oxidation of vanadyl sulfate to N,N′-dimethylammonium decavanadate cluster and DNA, BSA binding, and cytotoxicity (HeLa) studies

Several polymetallic anionic clusters display a strong tendency to form robust ion-pairs with appropriate counter cations. We have isolated decavanadate cluster [H2V10O28]4– with, hitherto unreported, dimethylammonium ions, [N(CH3)2H2]4+ as counter cations from vanadyl sulfate and N,N’-dimethylformamide (DMF). It is proposed, for the first time, that dimethylammonium ions are formed by reduction and simultaneous decarboxylation of DMF with oxidation of vanadyl sulfate occurring concomitantly under specified reaction conditions. The different colors observed during the course of the reaction are monitored by UV-Visible spectrophotometry. The structure of isolated cluster compound with four counter cations is confirmed by single crystal X-ray diffraction techniques. The compound is also tested for its DNA/BSA binding efficacy and cytotoxicity on human epitheloid cervix carcinoma (HeLa) cells along with vanadates—vanadium pentoxide and ammonium metavanadate. Based on the results, the cluster shows better IC50 and binding values than vanadates.

Pharmacokinetics and tissue distribution of N-(2-hydroxyphenyl)-2-propylpentanamide in Wistar Rats and its binding properties to human serum albumin

N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) is a novel valproic acid derivative that has shown anti-proliferative activity against epitheloid cervix carcinoma (HeLa), rhabdomyosarcoma (A204), and several breast cancer cell lines. The aim of this research was to evaluate the pharmacokinetic profile and tissue distribution of HO-AAVPA in Wistar rats, as well as its human serum albumin binding potential by experimental and in silico methods. A single dose of HO-AAVPA was given to male rats by intravenous, intragastric or intraperitoneal routes at doses of 25, 100, and 100 mg/kg, respectively. Then, blood samples were drawn at predetermined intervals of time, and the HO-AAVPA concentration in the plasma was quantified with a validated HPLC method. The elimination half-life (t1/2) was approximately 222 min, and the systemic clearance (CL) and apparent volume of distribution (Vd) were 2.20 mL/min/kg and 0.70 L/kg, respectively. The absolute oral bioavailability of HO-AAVPA was 33.8%, and the binding rate of HO-AAVPA with rat plasma proteins was between 66.2% and 83.0%. Additionally, in silico, UV and Raman spectroscopy data showed weak interactions between the test compound and human serum albumin. Thus, the results that were obtained demonstrated that despite its low oral bioavailability, the potential anticancer agent HO-AAVPA exhibits acceptable pharmacokinetic properties that would allow it to reach its site of action and exert its pharmacological effect in Wistar Rats, and it has a convenient profile for future assays to evaluate its human applications.

Polyphenolic composition, antioxidant and antiproliferative effects of wild and cultivated blackberries (Rubus fruticosus L.) pomace

SummaryThe content of total polyphenolics, antioxidative capacity and antiproliferative activity were tested in wild and cultivated blackberry pomace. Wild blackberry pomace extract Tw2 showed the highest following contents: total polyphenolics (50.16 mg GAE g−1 dw), flavonoids (7.73 mg Qc g−1 dw), flavonols (6.63 mg Qc g−1 dw) and total monomeric anthocyanins (13.40 mg Cy g−1). Tw2 extract significantly inhibited free radicals: IC50DPPH = 127.76 μg mL−1, IC50ABTS = 26.53 μg mL−1 and IC50˙OH = 168.62 μg mL−1, and the growth of breast adenocarcinoma IC50MCF7 = 306.68 μg mL−1 and cervix epitheloid carcinoma cell lines IC50HeLa = 315.49 μg mL−1. Wild blackberry varieties had higher extraction yields, higher total polyphenolic contents and possessed stronger biological effects compared to cultivated blackberries (P < 0.05). All blackberry extracts showed high biological potential that could be attributed to high total polyphenols and flavonoids content and could be utilised as value‐added functional food.

Cellular oxidative stress and antiproliferative effects of Cordia dichotoma (Linn.) seeds extract and their fractions on human cervix epitheloid (HeLa) and human lung (A549) carcinoma cells

IntroductionCordia dichotoma (Linn.) is an ethnobotanically important plant species traditionally used for the treatment of several diseases in humans. The present study was aimed to explore the oxidative and anticancer properties of Cordia dichotoma seeds extract (MECD) along with its fractions against Human Cervix Epitheloid (HeLa) and human lung (A549) carcinoma cell lines. MethodsCrude extract of Cordia dichotoma seeds was prepared in methanol by continuous hot soxlation technique and the extract was concentrated to dryness. For the purpose of standardization of crude extract, HPTLC profiling of extract was done and finally, three different fractions namely chloroform, ethyl acetate, and the aqueous fraction was prepared using column chromatography. The cellular oxidative stress potential was measured in the term of intracellular reactive oxygen species (ROS) levels whereas anti-proliferative potential was evaluated by cell viability (MTT) assay, nuclear staining assays such as PI-Exclusion and Hoestch/PI double staining for the analysis of induction of apoptosis. Cellular morphology was also performed using inverted phase contrast microscope and percentage apoptosis along with apoptotic cell ratio was calculated. ResultsExposure to crude extract and their fractions in the dose ranging from 25 μg/mL to 250 μg/mL, significantly inhibited the cell viability (p < 0.001) in a dose-dependent manner. Fluorescence microscopy analysis and intracellular ROS generation exhibited significant ROS induction that might trigger the apoptotic pathways leading to the death of cancerous cells. ConclusionOur results suggest that the methanolic extract of Cordia dichotoma seeds as well as its aqueous fraction possesses maximum cytotoxicity against human cervix epitheloid (HeLa) and human lung (A549) cancer cell lines.

Chemical constituents of Silene montbretiana

A new steroidal glycoside, 3-O-β-d-glucopyranosyl-3β,25-dihydroxy-5β-cholest-7-en-6-one 25-O-β-d-glucopyranoside (1), together with six known steroidal derivatives (2-7), one cerebroside (8) and one flavonoid (9) were isolated from Silene montbretiana Boiss (Caryophyllaceae), a perennial herb growing mainly in the Middle and East Anatolia, Azerbaijan, Iran, and Turkey. Their structures were established by the extensive use of 1D and 2D NMR experiments along with ESI-MS analyses. The cytotoxicity against the cancer A549 (human alveolar basal carcinoma) and Hela (human epitheloid cervix carcinoma) cell lines has been evaluated. None of the tested compounds, in a range of concentrations between 12.5 and 100 μM, caused a significant reduction of the cell number.

Amberlite IR-120 (H) mediated “on water” synthesis of fluorescent Ruthenium(II)-arene 8-hydroxyquinoline complexes for cancer therapy and live cell imaging

A series of Ruthenium-Quinolinol complexes (3a–d &4a–d) has been synthesized by employing a simple, efficient and environmental friendly condition. Catalytic role of Amberlite IRA-120(H) has been demonstrated. The structures of the new compounds were elucidated by the analysis of spectroscopic data. The stability of these complexes was measured by UV spectroscopy & time dependent NMR spectroscopy. These newly developed complexes were represented as potential anticancer agent against human breast carcinoma cell line (MCF-7), human Epitheloid Cervix Carcinoma (HeLa), human lung adenocarcinoma epithelial cell line (A549) and human colon cancer cell line (Caco-2). Most of the ruthenium complexes showed higher anticancer activity in MCF-7, HeLa and Caco-2 cell lines than cisplatin. A high selectivity (9–28 folds) was observed with these newly developed organoruthenium compounds in human cancer cell lines (MCF-7, HeLa and Caco-2) with respect to normal fibroblast cell line (MRC-5). Complex [(η6-hexamethylbenzene)RuCl(κ2-O,N-5-chloro-HyQ)]·Cl (4b), [(η6-hexamethylbenzene)RuCl(κ2-O,N-5,7-dibromo-HyQ)]·Cl (4c) and [(η6-hexamethylbenzene)RuCl(κ2-O,N-5-chloro-7-iodo-HyQ)]·Cl (4d) exhibited best cytotoxicity profiles in three reported human cancer cell lines (MCF-7, HeLa, Caco-2). Cellular imaging study was also performed with these newly developed organoruthenium compounds. Compound 4c might be utilized for cancer theranostic agents because of its significant quantum yield in water, high potency, selectivity and high cellular uptake in cancer cell lines.

Superparamagnetic LaSrMnO3 nanoparticles for magnetic nanohyperthermia and their biocompatibility

The nanohyperthermia investigation of superparamagnetic La0.77Sr0.23MnO3 nanoparticles synthesized by hydrothermal method has been carried out. The synthesized nanoparticles are found to be highly uniform in size and shape with average particle size 18nm. Structural analysis confirms the pseudo-cubic perovskite crystal structure with space group of (R3c). The magnetization versus applied magnetic field (M-H) hysteresis loops measurements revealed the superparmagnetic nature of the synthesized nanoparticles. The induction heating of synthesized nanoparticles for their applications in nanohyperthermia has been studied. The in vitro cytotoxicity test of the synthesized superparamagnetic nanoparticles has been probed by evaluating the viability of HeLa (Human Negroid Cervix Epitheloid Carcinoma) cell lines. The mechanism responsible for nanohyperthermia heating of the synthesized nanoparticles has been discussed.

Isolation of antioxidant phenolics from Schinopsis brasiliensis based on a preliminary LC-MS profiling

The phenolic content of the ethanol extract of the stem bark of the Brazilian plant Schinopsis brasiliensis Engl. (Anacardiaceae) has been evaluated together with the antioxidant activity. The good antioxidant activity exhibited in the Trolox Equivalent Antioxidant Capacity (TEAC) assay (TEAC value = 3.04 mg/mL) encouraged us to investigate its constituents. An analytical approach based on LC-ESIMSn was applied to rapidly obtain a metabolite profile of the ethanol extract of the stem bark of S. brasiliensis. Sixteen phenolic compounds, among which five galloyl derivatives, never reported before, have been isolated and their structures have been unambiguously elucidated by extensive spectroscopic methods, including 1D (1H, 13C, TOCSY) and 2D (DQF-COSY, HMBC, and HSQC) NMR experiments. Moreover, the antioxidant activity of all the isolated compounds was evaluated, along with the cytotoxicity against the cancer cell lines A549 (human alveolar basal carcinoma) and Hela (human epitheloid cervix carcinoma). The previously undescribed compounds exhibited a high free-radical-scavenging activity, in the range of 1.10–1.86 mM.None of the tested compounds, in a range of concentrations between 12.5 and 100 μM, caused a significant reduction of the cell number.

Chemical composition and bioactivity of essential oils from flower and fruit of Thymbra capitata and Thymus species.

Thymbra capitata and Thymus species are commonly known as thyme in Spain and they are currently used as culinary herbs, as well as for ornamental, aromatizing and traditional medicinal purposes. Given the economic importance of thyme oils, many thyme species have been studied, and their essential oils (EOs) and other volatile-containing extracts have been chemically characterized. The aim of this study was to evaluate the antioxidant, antimicrobial and cytotoxic activities as well as the phytochemical composition of the EOs from fruits and flowers of T. capitata and Thymus species. High antioxidant capacity has been observed and related to the relative amounts of terpenoid and phenolic with good antioxidant properties. The antioxidant activities decreased as follows: TAC>TZ>TC>TM. The results of antimicrobial activity showed that all tested EOs were active against all tested microbial species, including Gram-positive and negative bacteria. The minimum inhibition concentration values obtained ranged from 0.1 to 0.01μL/mL. Furthermore, all EOs assayed induced cell death in both human epitheloid cervix carcinoma and histiocytic leukemia cell lines. Overall, the results of this study indicates that the EOs from fruits and flowers of T. capitata and Thymus species posses interesting antioxidant properties and represent a potential source of medicine for the treatment of infectious diseases and cancer.

Cytotoxicity Study of Cyclopentapeptide Analogues of Marine Natural Product Galaxamide towards Human Breast Cancer Cells.

Herein, we report the cytotoxicity of cyclopentapeptide analogues of marine natural product galaxamide towards breast carcinoma cells and the underlying mechanisms. We examined the effect of the novel galaxamide analogues on cancer cell proliferation by MTT assay and also further examined the most active compound for morphological changes using Hoechst33342 staining technique, induction of apoptosis, cell cycle phases, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) generation using flow cytometry in human breast cancer MCF-7 cells in vitro. Galaxamide and its analogues effectively induced toxicity in human hepatocellular carcinoma HepG2, human breast carcinoma MCF-7, human epitheloid cervix carcinoma HeLa, and human breast carcinoma MB-MDA-231 cell lines. Amongst them, compound 3 exhibited excellent toxicity towards MCF-7 cells. This galaxamide analogue significantly induced apoptosis in a dose-dependent manner in MCF-7 cells involves cell cycle arrest in the G1 phase, a reduction of MMP, and a marked increase in generation of ROS. Particularly, compound 3 of galaxamide analogues might be a potential candidate for the treatment of breast cancer.

Synthesis and cytotoxicity study of novel 3-(triazolyl)coumarins based fluorescent scaffolds

Recently a choice of fluorescent bioimaging probes have been developed as medical diagnostic tools. Herein, we have introduced a series of coumarin-based target specific probes for cancer theranostic application which play a dual role in the field of both diagnosis and therapy. A fluorogenic version of 1,3-dipolar cycloaddition between azides and alkynes (DBCO) has been introduced to develop the triazolylcoumarin based fluorescent scaffolds. These scaffolds were screened for their anticancer activity against breast cancer (MCF7) and human epitheloid cervix carcinoma (HeLa) cell line. It was established that triazolylcoumarins (5c and 5d) are having electronegative substitution in the benzene ring displayed most effective anticancer profile in both the cell lines. Compounds 5a and 5d exhibited maximum quantum yield and strong cellular uptake in the MCF-7 cell line.

Non-symmetric CNS-Pt(II) pincer complexes including thioether functionalized iminophosphoranes. Evaluation of their in vitro anticancer activity

Iminophosphoranes of general formula Ph3P = NC6H4SR [R = 4-C6H4NO2 (3) and CH2C6H5 (4)], combining the iminophosphorane group with a thioether moiety were synthesized and fully characterized, including the unequivocal determination of the solid state structure of ligand (3) by single crystal X-ray diffraction techniques. These ligands and other related [R = CH3 (1), C6H5 (2)] were further reacted with [Pt(S(CH3)2)2Cl2] to produce, in all cases, the non-symmetric CNS-Pt(II) pincer complexes [PtCl{C6H4(Ph2P = NC6H4SR–κ3–C,N,S)}] [R = CH3 (5), C6H5 (6), 4-C6H4NO2 (7), CH2C6H5 (8)]. All compounds were fully characterized using common analytical techniques and the solid state structures of (5), (6) and (7) were unequivocally determined by single crystal X-ray diffraction experiments. The in vitro antiproliferative activity of these new species was explored against a series of tumoral cell lines [U251 (human glioblastoma), PC-3 (human prostate cancer cell line), K562 (human leukemia), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human breast adenocarcinoma), SKLU (human lung adenocarcinoma) and HeLa (epitheloid cervix carcinoma)] showing compounds 5 (R = CH3) and 8 (R = CH2C6H5) to have better cytotoxic activity than cisplatin against HeLa and K562 tumoral cell lines.

Intracellular uptake and fluorescence imaging potential in tumor cell of zinc phthalocyanine

A near IR absorbing phthalocyanine bearing four binaphtyl group has been synthesized in order to investigate its cytotoxicity and intracellular uptake of sensitizer on MCF-7 (human breast cancer), MDAH (ovarian cancer), HeLa (human epitheloid cervix carcinoma), EMT-6 (mouse breast cancer) and WI-38 (human fibroblast lung) cell lines. ZnPc showed four time higher intracellular uptake in carcinoma cells (MCF-7) than normal (WI-38) cell lines. With the aim of studying in detail the biodistribution feature and tumor nuclear imaging capacity, ZnPc was also labeled with I-131. The efficiency of radiolabeled compound was 95±4.6%. In addition, ZnPc reveals to be very efficient singlet oxygen generators (ΦΔ=0.612 in DMSO) and promising PS for PDT application. In vitro fluorescence imaging study with MCF-7 cells showed that ZnPc localized in cytoplasm of the cells. This results showed that synthesized ZnPc is promising candidate for dual fluorescence/nuclear imaging breast cancer and shows potential PS for PDT application.

Synthesis of novel anticancer ruthenium–arene pyridinylmethylene scaffolds via three-component reaction

A novel three components approach for the synthesis of bioactive Ru–arene pyridinylmethylene complexes has been developed using pyridine carboxaldehyde, amino pyridine and dichloro (p-cymene) ruthenium(II) dimer as starting materials. These scaffolds were screened for their anticancer activity against breast cancer (MCF7) and human Epitheloid Cervix Carcinoma (HeLa) cell line. It was established that compounds [(η6-pcymene)RuCl(κ2-N,N-(3,5-dinitro-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4o), [(η6-pcymene)RuCl(κ2-N,N-N-(3,5-dibromo-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4c), [(η6-pcymene)RuCl(κ2-N,N-(3,5-dibromo-6-methylpyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4j) and [(η6-pcymene)RuCl(κ2-N,N-3(3-bromo-5-methyl-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4b) were significantly active against both the cell lines.

Dichlorido-platinum(II) complexes with kinetin derivatives as promising cytotoxic agents avoiding resistance of cancer cells: Contrasting results between cisplatin and oxaliplatin analogues

With the aim to study the anticancer potential and compare the influence of different leaving groups, dichlorido and oxalato (ox) platinum(II) complexes involving di- and tri-substituted derivatives of a plant hormone kinetin (N6-furfuryladenine; Ln) were prepared: cis-[PtCl2(L1)2]·H2O (1), trans-[PtCl2(L1)2] (1a), cis-[PtCl2(L2)2]·0.75H2O (2), and [Pt(L1)2(ox)] (3), [Pt(L2)2(ox)] (4), with 2-chloro-N6-furfuryl-9-isopropyladenine (L1) and 2-chloro-N6-(5-methylfurfuryl)-9-isopropyladenine (L2). The complexes were structurally characterized by elemental and thermal analyses, FT-IR and 1H, 13C, 15N and 195Pt NMR spectroscopy, ESI+ mass spectrometry, conductivity measurements as well as single crystal X-ray diffraction (for 1). The Ln carrier ligands act as monodentate N-donors coordinated to the platinum(II) centre, which reveals a slightly distorted square-planar geometry. All the prepared complexes were screened for their in vitro cytotoxicity against breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines. This preliminary study identified only the cis-dichlorido-Pt(II) complexes 1, 2 as cytotoxic agents. These two complexes were thus further evaluated for in vitro cytotoxicity against malignant melanoma (G-361), cervix epitheloid carcinoma (HeLa), cisplatin sensitive (A2780) and resistant (A2780R) ovarian carcinoma human cancer cell lines. Most importantly, the obtained results showed that the cis-[PtCl2(Ln)2]·xH2O complexes were able to circumvent cisplatin resistance in A2780R cells while additionally being significantly more cytotoxic against A2780 than cisplatin, as demonstrated by the resistance factors IC50(A2780R)/IC50(A2780) equal to 0.87 for 1; 0.48 for 2 as compared to 2.25 for cisplatin. The complexes were furthermore comparably active against HOS, MCF7, G-361 cells as cisplatin. In order to address the contrasting cytotoxic results of the cisplatin (1, 2) and oxaliplatin (3, 4) analogues, their possible fate in the physiological environment, focusing on the hydrolytic stability and interactions with glutathione and 5′-guanosine monophosphate, was studied by means of 1H NMR spectroscopy.