HCT116 Human Colon Carcinoma Research Articles

Design, Synthesis, and Biological Evaluation of Triazolyl- and Triazinyl-Quinazolinediones as Potential Antitumor Agents

Novel 6(3-1H-1,2,4-triazol-1-yl)-3-phenylquinazoline-2,4(1H,3H)-diones (7a–e) were synthesized from different enaminones (6a–e) with 6-hydrazinyl-3-phenylquinazoline-2,4(1H,3H)-dione. 2,6(4-2-Substituted-1,3,5-triazin-1(2H)-yl)-3-phenylquinazoline-2,4(1H,3H)-diones (8a–k) were synthesized from the reaction of 1-(2,4-dioxo-3-phenyl-1,2,3,4-tetrahydroquinazolin-6-yl)thiourea, urea, or guanidine (3a–c) with enaminones (6a–e), and a series from 3-substituted-2-imino-1,3,5-triazin-1(2H)-yl-sulfonyl-phenyl-1-methylquinazoline-2,4(1H,3H)-dione (12a–j) were obtained from the reaction of N-(diaminomethylene)-4-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)benzenesulfonamide (11) with the enaminone (6a–j). The antitumor activity of the synthesized compounds was evaluated against two human cell lines: human colon carcinoma HCT116 and human hepatocellular carcinoma HEP-G2. Some of the tested compounds showed significant potency compared to the reference drug staurosporin.

Discovery and Structure-Activity Relationships of N-Aryl 6-Aminoquinoxalines as Potent PFKFB3 Kinase Inhibitors.

Energy and biomass production in cancer cells are largely supported by aerobic glycolysis in what is called the Warburg effect. The process is regulated by key enzymes, among which phosphofructokinase PFK-2 plays a significant role by producing fructose-2,6-biphosphate; the most potent activator of the glycolysis rate-limiting step performed by phosphofructokinase PFK-1. Herein, the synthesis, biological evaluation and structure-activity relationship of novel inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which is the ubiquitous and hypoxia-induced isoform of PFK-2, are reported. X-ray crystallography and docking were instrumental in the design and optimisation of a series of N-aryl 6-aminoquinoxalines. The most potent representative, N-(4-methanesulfonylpyridin-3-yl)-8-(3-methyl-1-benzothiophen-5-yl)quinoxalin-6-amine, displayed an IC50 of 14 nm for the target and an IC50 of 0.49 μm for fructose-2,6-biphosphate production in human colon carcinoma HCT116 cells. This work provides a new entry in the field of PFKFB3 inhibitors with potential for development in oncology.

RA-XXV and RA-XXVI, Bicyclic Hexapeptides from Rubia cordifolia L.: Structure, Synthesis, and Conformation.

Two RA-series bicyclic hexapeptides, RA-XXV (4) and RA-XXVI (5), which have no N-methyl group at Tyr-5, were isolated from the roots of Rubia cordifolia L. Their amino acid compositions and sequences were determined by interpretation of MS, and 1D and 2D NMR data and their relative structures were elucidated by XRD analysis of 4 and RA-XXVI acetate (6). The absolute stereochemistry of 4 was established by the total synthesis of 4, and that of 5, by the chemical correlation with 4. Peptides 4 and 5 exhibited cytotoxicity toward human promyelocytic leukemia HL-60 (IC50 =0.062 and 0.066 μm, respectively) and human colonic carcinoma HCT-116 (IC50 =0.028 and 0.051 μm, respectively) cell lines. Analysis of the conformational structures of 4 and 6 in the crystalline state and those of 4 and 5 in solution revealed that the N-methyl group at Tyr-5 functions to make this series of peptides preferentially adopt the active conformation.

2-Deoxy-D-glucose has distinct and cell line-specific effects on the survival of different cancer cells upon antitumor drug treatment.

The dependence of tumors on glycolysis for ATP generation offers a rationale for therapeutic strategies aimed at selective inhibition of the glycolytic pathway. Analysis of tumor cell responses to anticancer drugs revealed that inhibition of glycolysis by 2-deoxy-D-glucose (2-DG) generally augmented the apoptotic response; however, in HCT116 human colon carcinoma cells, apoptosis was suppressed. A comparison of neuroblastoma SK-N-BE(2) and HCT116 cells revealed, that in contrast to HCT116, in SK-N-BE(2) cells 2-DG alone was able to induce cell death. In SK-N-BE(2) cells the decrease in ATP levels upon treatment with 2-DG was more prominent because in HCT116 cells mitochondria compensated for the loss of ATP caused by glycolysis suppression. In both cells lines 2-DG triggered endoplasmic reticulum (ER) stress, assessed by the accumulation of the marker protein GRP78/BiP. Suppression of ER stress by mannose attenuated the 2-DG-induced apoptotic response in SK-N-BE(2) cells, implying that apoptosis in these cells is a consequence of ER stress induction. In HCT116 cells, ER stress stimulated autophagy, assessed by the accumulation of the lipidated form of LC3. The inhibitor of ER stress mannose attenuated autophagy and reversed 2-DG-mediated suppression of cisplatin-induced apoptosis. When autophagy in HCT116 cells was suppressed by bafilomycin, cisplatin-induced apoptosis was decreased. At the same time, stimulation of autophagy in SK-N-BE(2) cells suppressed cell death. Thus, successful treatment of tumors with conventionally used anticancer drugs should be combined with targeting metabolic pathways involved in the regulation of apoptosis, autophagy, and cellular bioenergetics.

Butyrate interacts with benzo[a]pyrene to alter expression and activities of xenobiotic metabolizing enzymes involved in metabolism of carcinogens within colon epithelial cell models

Butyrate helps to maintain colon homeostasis and exhibits chemopreventive effects in colon epithelium. We examined the interactive effects of butyrate and benzo[a]pyrene (BaP), dietary carcinogen, in regulation of expression of a panel of phase I and II xenobiotic metabolizing enzymes (XMEs) in human colon cells. In human colon carcinoma HCT-116 and HT-29 cell lines, butyrate alone increased mRNA levels of some enzymes, such as N-acetyltransferases (in particular NAT2). In combination with BaP, butyrate potentiated induction of cytochrome P450 family 1 enzymes (CYP1A1), aldo-keto reductases (AKR1C1) or UDP-glucuronosyltransferases (UGT1A1). There were some notable differences between cell lines, as butyrate potentiated induction of NAD(P)H:quinone oxidoreductase 1 (NQO1) and UGT1A4 only in HCT-116 cells, and it even repressed AKR1C3 induction in HT-29 cells. Butyrate also promoted induction of CYP1, NQO1, NAT2, UGT1A1 or UGT1A4 in human colon Caco-2 cells, in a differentiation-dependent manner. Differentiated Caco-2 cells exhibited a higher inducibility of selected XME genes than undifferentiated cells. Butyrate increased induction of enzymatic activities of NATs, NQO1 and UGTs by BaP in HCT-116 and HT29 cells, whereas in differentiated Caco-2 cells it helped to increase only enzymatic activity of NQO1 and UGTs. Together, the present data suggest that butyrate may modulate expression/activities of several enzymes involved in metabolism of carcinogens in colon. In some cases (NAT2, UGT1 A1), this was linked to inhibition of histone deacetylases (HDAC), as confirmed by using HDAC inhibitor trichostatin A. These results may have implications for our understanding of the role of butyrate in regulation of XMEs and carcinogen metabolism in colon.

Anticancer activity and phytochemical composition of wild Gundelia�tournefortii

Artichoke-like wild thistles are often used in Palestinian cuisine. One of the most commercially recognized species of these wild edible thistles is Gundelia tournefortii, a common plant in the Mediterranean region. G. tournefortii, or 'Akoob' in Arabic, remains uncultivated, harvested wild by local populations and considered highly valuable due to its reputed health benefits. The present study aimed to investigate the anticancer effects of G. tournefortii on the human colon carcinoma HCT-116 cell line. Methanol and hexane extracts were identified to exert considerable antitumor activity against the HCT-116 cancer cell line, while the aqueous extract was inactive. The phytochemical profiles of the methanol and hexane extracts were investigated using gas chromatography-mass spectrometry. A total of 6 of the 27 natural compounds identified, including sitosterol, stigmasterol, lupeol, gitoxigenin, α-amyrin and artemisinin, have been previously validated as being active against cancerous cells. Therefore, the presence of these phytochemicals in G. tournefortii is of importance in its role in preventing and treating cancer.

In Silico HCT116 Human Colon Cancer Cell-Based Models En Route to the Discovery of Lead-Like Anticancer Drugs

To discover new inhibitors against the human colon carcinoma HCT116 cell line, two quantitative structure–activity relationship (QSAR) studies using molecular and nuclear magnetic resonance (NMR) descriptors were developed through exploration of machine learning techniques and using the value of half maximal inhibitory concentration (IC50). In the first approach, A, regression models were developed using a total of 7339 molecules that were extracted from the ChEMBL and ZINC databases and recent literature. The performance of the regression models was successfully evaluated by internal and external validations, the best model achieved R2 of 0.75 and 0.73 and root mean square error (RMSE) of 0.66 and 0.69 for the training and test sets, respectively. With the inherent time-consuming efforts of working with natural products (NPs), we conceived a new NP drug hit discovery strategy that consists in frontloading samples with 1D NMR descriptors to predict compounds with anticancer activity prior to bioactivity screening for NPs discovery, approach B. The NMR QSAR classification models were built using 1D NMR data (1H and 13C) as descriptors, from 50 crude extracts, 55 fractions and five pure compounds obtained from actinobacteria isolated from marine sediments collected off the Madeira Archipelago. The overall predictability accuracies of the best model exceeded 63% for both training and test sets.

PH-Responsive hyaluronated liposomes for docetaxel delivery

In this study, we report pH-responsive liposomes consisting of hydrogenated soy phosphatidylcholine (HSPC) as a lipid, hyaluronic acid (HA) grafted with functional 3-diethylaminopropyl (DEAP) groups (hereafter denoted as HA-g-DEAP) as a pH-responsive polymer, and docetaxel (DTX) as an antitumor drug. DTX-loaded HSPC liposomes were prepared via a conventional liposome manufacturing procedure and then were decorated with HA-g-DEAP (HA-g-DEAP0.15, HA-g-DEAP0.25, and HA-g-DEAP0.40, according to the molar conjugate ratio of DEAP to HA) in an aqueous solution (pH 7.4), by sonication. The liposomes with HA-g-DEAP0.40 allowed the efficient release of the encapsulated DTX content when the pH of the solution decreased to 6.5 (i.e., endosomal pH), owing to the acidic pH-induced protonation of the DEAP anchored to the vesicular lipid bilayers. These hyaluronated liposomes were effective at entering the human colon carcinoma HCT-116 cells with a CD44 receptor overexpression. In an in vitro tumor cell cytotoxicity test, the DTX-loaded liposomes caused a significant increase in HCT-116 tumor cell death, revealing their pharmaceutical potential in tumor therapy.

CJK-7, a Novel Flavonoid from Paulownia tomentosa Triggers Cell Death Cascades in HCT-116 Human Colon Carcinoma Cells via Redox Signaling.

Colon cancer is the second most common cancer to cause death worldwide. About half of colon cancers patients require adjuvant therapy to control relapse following surgical resection. Therefore, abolition of tumor cell progression using an effective chemotherapeutic agent holds a feasible approach to treat patients suffering from colon cancer. In the present study, we evaluated the effects of geranylated flavonoid CJK-7, isolated from Paulownia tomentosa on HCT-116 human colon carcinoma cells. The effects of CJK-7 as an active component on HCT-116 cells programmed cell death and its underlying molecular mechanism were examined by using MTT assay, morphological assessment, H2DCFDA staining, Fura-2AM staining, Hoechst-33342 staining, comet assay, Acridine orange staining, mitochondrial membrane potential (ΔΨm) assay and Western blot analyses. The results revealed that, CJK-7 was capable of inducing caspase-dependent cell death events in cancer cells. Moreover, it was involved in up-regulation of autophagy signaling as evidenced by enhanced expression of LC3I/II. We also noticed stimulated expression of endoplasmic reticulum stress markers and phosphorylation of c-Jun NH2-terminal kinase (JNK), which was associated with up-regulated expression of p53, PUMA, Atg5 and Beclin-1, and down-regulation of Bcl-2, stressing the interaction of ROS on the aforementioned signaling. Furthermore, exposure to ROS scavengers (N-acetyl-l-cysteine (NAC), and JNK-specific inhibitor SP600125) significantly reversed the effects of CJK-7 by down-regulating apoptosis and autophagy signatures in HCT-116 cancer cells. Collectively our findings clarify the ROS-dependent regulatory effect of CJK-7 on programmed cell death signaling events in HCT-116 cancer cells while depicting its virile pro-oxidant capacity.

ROS modifiers and NOX4 affect the expression of the survivin-associated radio-adaptive response

The survivin-associated radio-adaptive response can be induced following exposure to ionizing radiation in the dose range from 5 to 100 mGy, and its magnitude of expression is dependent upon the TP53 mutational status of cells and ROS signaling. The purpose of the study was to investigate the potential role of ROS in the development of the survivin-associated adaptive response. Utilizing human colon carcinoma HCT116 TP53 wild type (WT) and HCT116 isogenic TP53 null mutant (Mut) cell cultures, the roles of inter- and intracellular ROS signaling on expression of the adaptive response as evidenced by changes in intracellular translocation of survivin measured by ELISA, and cell survival determined by a standard colony forming assay were investigated using ROS modifying agents that include emodin, N-acetyl-L-cysteine (NAC), fulvene-5, honokiol, metformin and rotenone. The role of NADPH oxidase 4 (NOX4) in the survivin-associated adaptive response was investigated by transfecting HCT116 cells, both WT and Mut, with two different NOX4 siRNA oligomers and Western blotting. A dose of 5 mGy or a 15 min exposure to 50 µM of the ROS producing drug emodin were equally effective in inducing a pro-survival adaptive response in TP53 WT and a radio-sensitization adaptive response in TP53 Mut HCT116 cells. Each response was associated with a corresponding translocation of survivin into the cytoplasm or nucleus, respectively. Exposure to 10 mM NAC completely inhibited both responses. Exposure to 10 µM honokiol induced responses similar to those observed following NAC exposure in TP53 WT and Mut cells. The mitochondrial complex 1 inhibitor rotenone was effective in reducing both cytoplasmic and nuclear survivin levels, but was ineffective in altering the expression of the adaptive response in either TP53 WT or Mut cells. In contrast, both metformin and fulvene-5, inhibitors of NOX4, facilitated the reversal of TP53 WT and Mut adaptive responses from pro-survival to radio-sensitization and vice versa, respectively. These changes were accompanied by corresponding reversals in the translocation of survivin to the nuclei of TP53 WT and to the cytoplasm of TP53 Mut cells. The potential role of NOX4 in the expression of the survivin-associated adaptive response was investigated by transfecting HCT116 cells with NOX4 siRNA oligomers to inhibit NOX4 expression. Under these conditions NOX4 expression was inhibited by about 50%, resulting in a reversal in the expression of the TP53 WT and Mut survivin-associated adaptive responses as was observed following metformin and fulvene-5 treatment. Exposure to 5 mGy resulted in enhanced NOX4 expression by about 40% in both TP53 WT and Mut cells, in contrast to only a 1–2% increase following a 2 Gy only exposure. Utilizing mixed cultures of HCT116 TP53 WT and isogenic null Mut cells, as few as 10% TP53 Mut cells were sufficient to control the expression of the remaining 90% WT cells and resulted in an overall radio-sensitization response accompanied by the nuclear translocation of survivin characteristic of homogeneous TP53 Mut populations.

Quinonoid compounds via reactions of lawsone and 2-aminonaphthoquinone with α-bromonitroalkenes and nitroallylic acetates: Structural diversity by C-ring modification and cytotoxic evaluation against cancer cells

Morita-Baylis-Hillman acetates and α-bromonitroalkenes have been employed in cascade reactions with lawsone and 2-aminonaphthoquinone for the one-pot synthesis of heterocycle fused quinonoid compounds. The reactions reported here utilized the 1,3-binucleophilic potential of hydroxy- and aminonaphthoquinones and the 1,2/1,3-bielectrophilic potential of bromonitroalkenes and Morita-Baylis-Hillman acetates for the synthesis of pyrrole and furan fused naphthoquinones. The synthesized compounds were evaluated against HCT-116 (human colon carcinoma cells), PC3 (human prostate cancer cells), HL-60 (human promyelocytic leukemia cells), SF295 (human glioblastoma cells) and NCI-H460 (human lung cancer cells) and exhibited antitumor activity with IC50 values as low as < 2 μM. Selected compounds were also evaluated against OVCAR-8 (ovary), MX-1 (breast) and JURKAT (leukemia) cell lines. The cytotoxic potential of the quinones evaluated was also assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC) and L929 cells.

Anti-Cancer Activity of Lobaric Acid and Lobarstin Extracted from the Antarctic Lichen Stereocaulon alpnum.

Lobaric acid and lobarstin, secondary metabolites derived from the antarctic lichen Stereocaulon alpnum, exert various biological activities, including antitumor, anti-proliferation, anti-inflammation, and antioxidant activities. However, the underlying mechanisms of these effects have not yet been elucidated in human cervix adenocarcinoma and human colon carcinoma. In the present study, we evaluated the anticancer effects of lobaric acid and lobarstin on human cervix adenocarcinoma HeLa cells and colon carcinoma HCT116 cells. We show that the proliferation of Hela and HCT116 cells treated with lobaric acid and lobarstin significantly decreased in a dose- and time-dependent manner. Using flow cytometry analysis, we observed that the treatment with these compounds resulted in significant apoptosis in both cell lines, following cell cycle perturbation and arrest in G2/M phase. Furthermore, using immunoblot analysis, we investigated the expression of cell cycle and apoptosis-related marker genes and found a significant downregulation of the apoptosis regulator B-cell lymphoma 2 (Bcl-2) and upregulation of the cleaved form of the poly (ADP-ribose) polymerase (PARP), a DNA repair and apoptosis regulator. These results suggest that lobaric acid and lobarstin could significantly inhibit cell proliferation through cell cycle arrest and induction of apoptosis via the mitochondrial apoptotic pathway in cervix adenocarcinoma and colon carcinoma cells. Taken together, our data suggests that lobaric acid and lobarstin might be novel agents for clinical treatment of cervix adenocarcinoma and colon carcinoma.

Colon cancer cells adhesion on polymeric nanostructured surfaces

Abstract

Analysis of ruthenium anticancer agents by MEEKC-UV and MEEKC-ICP-MS: Impact of structural motifs on lipophilicity and biological activity.

We present here the first comprehensive study on the lipophilicity of ruthenium anticancer agents encompassing compounds with broad structural diversity, ranging from octahedral RuIII (azole) through to RuII (arene) complexes. MEEKC was used to determine the capacity factors of the Ru complexes, and after a complex peak was unambiguously assigned using MEEKC-ICP-MS, the results were validated through comparison with the log P determined by octanol/water partitioning experiments. Correlation of the two data sets demonstrated a close relationship despite the limited structural overlap of the compounds studied. The capacity factors found by MEEKC allowed for the clustering of complexes based on their structure and this could be used to rationalize the observed cytotoxicity in the human colon carcinoma HCT116 cell line. It was demonstrated that rather than modification of the mono- or bidentate coordinated ligands much tighter control over a complexes lipophilic properties could be achieved through modification of the Ru(arene) ligand, with minimal detriment to cytotoxicity. This demonstrates the flexibility and potential of the Ru piano-stool scaffold. MEEKC proved to be a highly efficient means of screening the anticancer potential of preclinical ruthenium complex candidates for their lipophilic properties and correlate them with their biological activity and structural properties.

In vitro study of iron coordination properties, anti-inflammatory potential, and cytotoxic effects of N-salicylidene and N-vanillidene anil Schiff bases

N-Salicylidene and N-vanillidene anil Schiff bases SB-1–5 were evaluated for their iron-coordinating properties. For this purpose, reactions with Fe(III) chloride were performed. The obtained results showed that salicylaldehyde bases SB-1 and SB-2 are the best coordinating ligands among the investigated SBs. The corresponding complexes are obtained in good yield and investigated using UV–Vis spectrophotometry and IR spectroscopy. The inhibitory potential of SB-1–5 against iron-containing enzyme lipoxygenase (LOX) was also tested. Salicylidene bases exerted better activity then vanilliden. The cytotoxic in vitro activities against human breast carcinoma MDA-MB-231 and human colon carcinoma HCT-116 cell lines were determined. Based on these results, SB-1 and SB-2 can be considered as interesting compounds for further in vivo investigations.

Berberine regulates the microRNA-21-ITGΒ4-PDCD4 axis and inhibits colon cancer viability.

Berberine is sourced from multiple medicinal herb resources and is easy to extract. With the advantages of low price, safety and convenience, berberine may have potential for wide clinical use. The present study aimed to investigate whether berberine inhibited the viability of colon cancer and whether it regulated the three-gene network microRNA (miR)-21-integrin β4 (ITGβ4)-programmed cell death 4 (PDCD4). It was demonstrated that berberine treatment suppressed colon cancer cell viability, and induced apoptosis and activated caspase-3 activity in the human colon carcinoma HCT116 cell line. Berberine inhibited miR-21 expression and promoted ITGβ4 and PDCD4 protein expression in the HCT116 cell line. Overexpression of miR-21 reduced the anti-cancer effects of berberine on cell viability, apoptosis rate and caspase-3 activity of the HCT116 cell line. However, it was revealed that the overexpression of miR-21 also suppressed ITGβ4 and PDCD4 protein expression in the HCT116 cell line. In conclusion, miR-21, ITGβ4 and PDCD4 are involved in the anti-cancer effects of berberine on cell viability and apoptosis in the HCT116 cell line.

A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells

Combination of multifunctionalities into one compound is a rational strategy in medicinal chemical design, and have often been used with metallodrug-based compounds. In the present study, we synthesized a novel ruthenium-based 5-fluorouracil complex [Ru(5-FU)(PPh3)2(bipy)]PF6 (PPh3 = triphenylphosphine; and bipy = 2,2′-bipyridine) with enhanced cytotoxicity in different cancer cells, and assessed its apoptosis induction action in human colon carcinoma HCT116 cells. The complex was characterized by infrared, cyclic voltammetry, molar conductance measurements, elemental analysis, NMR experiments and X-ray crystallographic analysis. In both 2D and 3D cell culture models, the complex presented cytotoxicity to cancer cells more potent than 5-FU. A typical morphology of apoptotic cell death, increased internucleosomal DNA fragmentation, without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization and caspase-3 activation were observed in complex-treated HCT116 cells. Moreover, the pre-treatment with Z-DEVD-FMK, a caspase-3 inhibitor, reduced the apoptosis induced by the complex, indicating cell death by apoptosis through caspase-dependent and mitochondrial intrinsic pathways. The complex failed to induce reactive oxygen species production and DNA intercalation. In conclusion, the novel complex displays enhanced cytotoxicity to different cancer cells, and is able to induce caspase-mediated apoptosis in HCT116 cells.

Retraction.

1. Zhang G, Liu X, Li Y, Wang Y, Liang H, Li K, Li L, Chen C, Sun W, Ren S, Zhu P, Zhang L. EphB3-targeted regulation of miR-149 in the migration and invasion of human colonic carcinoma HCT116 and SW620 cells. Cancer Sci. 2017; 108: 408-418. https://doi.org/10.1111/cas.13161.

Synthesis, characterization and biological application of 5-quinoline 1,3,5-trisubstituted pyrazole based platinum(ii) complexes.

Square planar mononuclear platinum(ii) complexes were synthesized in the presence of neutral bidentate heterocyclic (5-quinoline 1,3,5-tri-substituted pyrazole scaffold) ligands and K2PtCl4 salt. The synthesized compounds were characterized by micro-elemental analysis, FT-IR, UV-vis, 1H NMR, 13C NMR, TGA, mass spectrometry and molar conductivity. Their biological activities were investigated by in vitro brine shrimp lethality bioassay, in vitro antimicrobial study against five different pathogens, in vivo cellular level cytotoxicity against Schizosaccharomyces pombe cells, and in vitro anti-proliferation assay. The binding constant Ksv, Kb, Ka values of the complexes were determined by DNA interaction studies. The gel electrophoresis assay was carried out to examine the effect of the complexes on the DNA nuclease of pUC19 plasmid DNA. The docking energies of the ligands (L1-L5 ) and complexes (I-V) were observed in the range of -265.14 to -284.33 kJ mol-1. The synthesized Pt(ii) complexes (I-V) were screened against the MCF-7 (human breast adenocarcinoma) and HCT-116 (human colon carcinoma) cancer cell lines.

Synthesis, Chemical Characterization, and Biological Screening for Cytotoxic and Antitumor Activityof Novel p-Chlorophenyl Maleanilic Acid and Its Corresponding Chelates

A novel p-chlorophenyl maleanilic acid ligand (L) was prepared from condensation reaction of maleic anhydride with p-chloroaniline. New synthesized organometallic chelates of the proposed general formula [M(CO)4L], where M = Cr, Mo or W, were prepared by reaction of metal hexa carbonyls condensation with bidentate maleanilic acid ligand in inert nitrogen atmosphere. The prepared novel ligand and its organometallic chelates were characterized by elemental analyses, FT-IR, mass spectra, 1H-NMR, and thermal analyses. The results obtained refer to an octahedral structure of the prepared organometallic chelates. The free ligand and its chromium chelate were screened for antitumor activity in vitro against cell lines of HCT-116 (human colon carcinoma), hepG-2 (human hepatocellular carcinoma), and MCF-7 (human breast carcinoma). The results obtained referred to a high antitumor activity of both novel ligand and its chromium chelate.