Anticancer Activity Of Compounds Research Articles

Two New Cu(II) and Zn(II)-Coordination Polymers Induce Gastric Cancer Cells Apoptosis via Upregulating ROS Related Genes

Two new coordination polymers, namely {[Cu(oba)(bpb)0.5](DMF)2}n [1, H2oba = 4,4′-oxybis(benzoic acid), bpb = 1,4-di(pyridin-4-yl)benzene] and {[Zn7(TPA)6(F)4(H2O)6](NO3)4(DMF)3}n (2, Htpa = 4-(1,2,4-triazol-4-yl)phenylacetic acid, DMF = N,N′-dimethylformamide) have been successfully constructed under solvothermal conditions. The in vitro anti-cancer activities of compounds 1 and 2 were evaluated on cancer cells in this study. The CCK-8 assay indicated both compounds 1 and 2 have excellent anti-cancer ability, but the activity of compound 1 is much stronger than compound 2. And the Annexin V-FITC/PI assay revealed that compounds exert anti-cancer effect via inducing cells apoptosis. Then, the further ROS assay revealed that the compound could induce human gastric cancer cells AGS apoptosis by up-regulating the ROS related genes and increasing the generation of ROS.

Design, Synthesis and Biological Evaluation of Ciprofloxacin- Peptide Conjugates as Anticancer Agents.

Cancer has emerged as a leading cause of death throughout the world. Peptides are a novel class of anticancer agents that can specifically target cancer cells with low toxicity to normal tissues and thus, offer new opportunities for future cancer treatment. On the other hand, Ciprofloxacin, an antibiotic, also known to its anticancer property for enabling cell cycle arrest and creating double strand breaks in nucleic acid can trigger apoptosis of cancer cells. Thus, joining anticancer peptides with Ciprofloxacin may be good idea to get benefit of the both compounds’ properties and therefore gives better anticancer agents. The aim of this study was to synthesize Ciprofloxacin- cytotoxic peptide conjugates and to investigate the anticancer activity of the resultant compounds. The conjugates were prepared by solid phase peptide synthesis technique using Fmoc strategy. Anticancer activity of these compounds was examined on three cancer cell lines, HT-29, MCF-7, MDA-MB-231 as well as skin fibroblast cells as a control, employing MTT test. Our results showed that the cytotoxic activity of the synthesized compounds against cancer cells was raised considerably without producing a high toxicity on normal cells. Moreover, Ciprofloxacin-peptide conjugates showed selectivity against different kinds of breast cancer cells, especially on those with triple negative receptors. Therefore, it can be suggested that the strategy of making Ciprofloxacin- peptide conjugates as cytotoxic agents with safety profiles on the normal cells, rise promise to find better chemotherapeutic candidates to combat cancer.

Cytotoxicity and apoptosis induction of sea cucumber Holothuria atra extracts

Context: Cancer is one of the major causes of death. Sea cucumbers are marine invertebrate that is widely used and utilized in traditional medicine. One of the most studied of sea cucumbers efficacy is its anticancer property. The anticancer property of sea cucumbers is much related to the content of an active compound called saponin. Objective: The objective of this research is to determine the cytotoxicity and apoptosis induction of sea cucumber Holothuria atra ethanol extract and to study its anticancer active compound. Materials and Methods: Sea cucumber of H. atra was taken from Halmahera waters, North Maluku Indonesia. The extraction was conducted by maceration method using ethanol 96% then continued with liquid-liquid partition and separation using C18 column. The investigation of active compound content was conducted by phytochemical and spectroscopic analysis using liquid chromatography-ion trap-time of a flight-mass spectrophotometer (LC-IT-ToF-MS). The cytotoxicity test was performed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide method against human breast ductal carcinoma cell (T47D), human breast adenocarcinoma (MCF7), human colorectal adenocarcinoma cell (WiDr), and human cervix adenocarcinoma cell lines (HeLa). The apoptotic induction test was performed using flow cytometry using Fluorescein isothiocyanate (FITC) Annexin-V-Apoptosis and caspase-3 detection using FITC Active Caspase-3 kit. Results: Phytochemical test showed that ethanol extract of H. atra contained alkaloids, flavonoids, steroids-triterpenoids, phenols, and saponins. The extract showed cytotoxic activity against the 4 cell lines with Inhibition concentration 50 values ranging from 9.6 to 14.3 μg/ml. Flow cytometry analysis showed that the T47D cell population underwent apoptosis after treated with ethanol extract. The extract also activated caspase-3 on the T47D cells. The results of LC-IT-ToF-MS analysis showed that the active fraction from C18 column separation contained saponin and identified as Cucumechinol and Philinopgenin B. Conclusions: The results of this study indicated that H. atra active extract has good cytotoxicity and has potential to be developed as an anticancer agent. Abbreviations used: MNPs: Marine natural products; LC-IT-ToF-MS: Liquid chromatography-ion trap-time of flight-mass spectrophotometer; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; T47D: Human breast ductal carcinoma cell; MCF7: Human breast adenocarcinoma cell; WiDr: Human colorectal adenocarcinoma cell; HeLa: Human cervix adenocarcinoma cell; RPMI: Roswell park memorial institute medium; FBS: Fetal bovine serum; FITC: Fluorescein isothiocyanate; PBS: Phosphate buffer saline; BD: Becton Dickinson; IC50: Inhibition concentration 50; PS: Phosphatidylserine; PI: Propidium iodide.

Synthesis, crystal structures of two novel metal coordination polymers and study of their inhibition of human hemangioma cells

In this work, two new InIII-based coordination polymers {(H2NMe2)3[In(TATAB)2](H2O)6}n (1, H3TATAB = 4,4',4''s-triazine-1,3,5-triyl-tri-p-aminobenzoic acid) and {(Me2NH2)2·[In2(TTA)2(FA)2](DMF)3}n (2, H3TTA = 4,4',4''-{[(2,4,6-trimethylbenzene-1,3,5-triyl)tris-(methylene)]tris(oxy)}tribenzoic acid, HFA = 2-fluorobenzoic acid, DMF = N,N-dimethyl­formamide) are successfully prepared under solvothermal conditions and structurally characterized by single crystal X-ray study (SCXRD) and powder X-ray analysis (PXRD). In addition, the in vitro anticancer activity of compounds 1 and 2 on three human hemangioma cells (HMEC-1, EAhy926 and SV40) is further investigated.

Two novel tungstate metal-organic complexes: Crystal structures and anticancer activity in osteogenic sarcoma

Two novel metal-organic compounds based on tungstate ― [Ni(HL1)2(Mo8O26)]⋅5H2O (1, L1 = 4-[5-(1H-pyrazol-4-yl)-4H-[1,2,4]triazol-3-yl]-pyridine) and [{Ni4(L2)4(H2O)6}(H3PMo12O40)]⋅7H2O (2, L2 = 2-(3-carboxypyridin-2-yl) nicotinic acid) ― are hydrothermally synthesized and characterized by single crystal X-ray diffraction as well as elemental analysis. In addition, the in vitro anticancer activity of compounds 1 and 2 on three human osteogenic sarcoma cells (MG63, U2OS, and 143B) is further determined via the MTT assay.

Two novel Ca(II)-carboxylate coordination polymers: Crystal structures and antimyeloma activity evaluation

In this study, two new coordination polymers [Ca3(BTB)2(NMP)2(H2O)2](NMP)(H2O)4 (1, H3BTB = benzene-1,3,5-tribenzoic acid, NMP = N-methyl-pyrrolidone) and [Ca3(NTB)2(DEF)2(H2O)2](DEF)(H2O)4 (2, H3NTB = 4,4',4''-nitrilotribenzoic acid, DEF = N,N-diethyl-formamide) based on the alkaline earth metal Ca(II) ion and two rigid C3-symmetric tricarboxylic acid ligands are successfully prepared via the solvothermal reaction. The structural analysis of complexes 1 and 2 demonstrates the existence of different topologies and structures in the as-prepared complexes because of the conformational flexibility of the organic ligands and the diverse geometry of the Ca(II)-based 1D secondary building unit. The particle sizes of these two complexes could be conveniently downsized in nanometer region via a simple treatment. In addition, in vitro anticancer activity of compounds 1 and 2 in nanometer has been studied for inhibition human myeloma cell growth via the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay.

Phenotype and target-based chemical biology investigations in cancers.

Chemical biology has been attracting a lot of attention because of the key roles of chemical methods and techniques in helping to decipher and manipulate biological systems. Although chemical biology encompasses a broad field, this review will focus on chemical biology aimed at using exogenous chemical probes to interrogate, modify and manipulate biological processes, at the cellular and organismal levels, in a highly controlled and dynamic manner. In this area, many advances have been achieved for cancer biology and therapeutics, from target identification and validation based on active anticancer compounds (forward approaches) to discoveries of anticancer molecules based on some important targets including protein-protein interaction (reverse approaches). Herein we attempt to summarize some recent progresses mainly from China through applying chemical biology approaches to explore molecular mechanisms of carcinogenesis. Additionally, we also outline several new strategies for chemistry to probe cellular activities such as proximity-dependent labeling methods for identifying protein-protein interactions, genetically encoded sensors, and light activating or repressing gene expression system.

Ethyl Acetate Fraction Of Secang As Anti Cervical Cancer By Inducing p53 and Caspase 9

Secang (Caesalpinia sappan L.) contains potentially anti-cancer active compounds, namely brazilin and brazilein which are soluble in ethyl acetate. This study is conducted to evaluate the anticancer activity of secang wood in cervical cancer cells (HeLa) in vitro and molecular mechanisms that selectively mediate their cytotoxic effects on several cancer cells through molecular docking or in silico. The anticancer potential of the ethyl acetate fraction of secang wood through its cytotoxic activity on HeLa cells was carried out with MTT assay and calculated the IC50 value. The molecular mechanism is carried out in silico with the target protein p53 and caspase 9 using the autodock 4.2 program. The docking process includes protein and active compounds preparation, validation of molecular docking methods and docking brazilein as the active substance with the target protein. The docking score is measured by binding energy value between brazilein and the target protein. The fraction of secang wood was cytotoxic in HeLa cells with IC50 values of 48.71 μg/mL. The docking results showed that brazilein had an affinity for the target proteins p53 and caspase 9 with binding energies of -8.24 and -6.71 kcal / mol, respectively.

Estudios efectivos de potencial para algunas nuevas moléculas híbridas para su actividad contra el cáncer de próstata

Objetivo: El presente trabajo tuvo como objetivo desarrollar nuevas moléculas híbridas para atacar el cáncer de próstata. Se observa que dos proteínas de choque humano, Hsp70 y Hsp90, se sobreexpresan en el cáncer de próstata, lo que las convierte en uno de los objetivos farmacológicos importantes. Hemos diseñado y desarrollado doce nuevas moléculas híbridas 6a-j para dirigir estas proteínas. Métodos: Las moléculas diseñadas se prepararon siguiendo un protocolo de reacción de cuatro etapas y se caracterizaron sobre la base de RMN de protón y espectrometría de masas. Estos se sometieron a estudios in vitro por medio de ensayos Oncotest y CCK-8 con dos líneas celulares DU145 y 22Rv1. Las moléculas seleccionadas 6b y 6i se sometieron a acoplamiento molecular y luego a ensayo de afinidad basado en SPR. Resultados: Se descubrió que los Compuestos 6b y 6i son compuestos anticancerígenos muy activos comparables al fármaco estándar enzalutamida. Tienen un IC50 significativo y una puntuación alta para el muelle de Hsp70 y Hsp90. Estos compuestos son selectivos y tienen una buena afinidad de unión por la Hsp70 debido a la alta Kd. Conclusión: Los compuestos 6b y 6i pueden servir como moléculas principales para el desarrollo de fármacos antiprostáticos contra el cáncer con Hsp70 como objetivo.

A novel anti-cancer role of β-apopicropodophyllin against non-small cell lung cancer cells

We previously reported that podophyllotoxin acetate (PA) inhibits the growth and proliferation of non-small cell lung cancer (NSCLC) cells and also makes them more sensitive to radiation and chemotherapeutic agents. In an attempt to enhance PA activity, we synthesized 34 derivatives based on podophyllotoxin (PPT). Screening of the derivative compounds for anti-cancer activity against NSCLC led to the identification of β-apopicropodophyllin (APP) as a strong anti-cancer agent. In addition to its role as an immunosuppressive regulator of the T-cell mediated immune response, the compound additionally showed anti-cancer activity against A549, NCI-H1299 and NCI-460 cell lines with IC50 values of 16.9, 13.1 and 17.1 nM, respectively. The intracellular mechanisms underlying the effects of APP were additionally examined. APP treatment caused disruption of microtubule polymerization and DNA damage, which led to cell cycle arrest, as evident from accumulation of phospho-CHK2, p21, and phospho-Cdc2. Moreover, APP stimulated the pro-apoptotic ER stress signaling pathway, indicated by elevated levels of BiP, phospho-PERK, phospho-eIF2α, CHOP and ATF4. We further observed activation of caspase-3, -8 and -9, providing evidence that both intrinsic and extrinsic apoptotic pathways were triggered. In vivo, APP inhibited tumor growth of NSCLC xenografts in nude mice by promoting apoptosis. Our results collectively support a novel role of APP as an anticancer agent that evokes apoptosis by inducing microtubule disruption, DNA damage, cell cycle arrest and ER stress.

Synthesis and characterization of triruthenium carbonyl incorporating 4-pyridones as potential antitumor agents

Four new organometallic triruthenium carbonyl incorporating 4-pyridones: [Ru3(CO)8(2L-2H)] (1, L = N-benzyl-3-hydroxy-2-methyl-4-pyridone; 2, L = 3-hydroxy-2-methyl-N-phenyl-4-pyridone; 3, L = 3-hydroxy-N,2-dimethyl-4-pyridone; 4, L = 2-methyl-4-pyridone) were synthesized and characterized. Proton NMR spectrum of 1 shows doublets for the two-nonequivalent benzylic hydrogens due to restricted rotation around C-N bond upon bonding to Ru(2)---Ru(3) as opposed to a singlet in the unbound N-benzyl-3-hydroxy-2-methyl-4-pyridone. Compounds 1 and 3 were characterized by X-ray diffraction analyses. Compounds 1 and 3 consists of two ruthenium-ruthenium bonds Ru(1)-Ru(2), Ru(1)-Ru(3) and a non-bonded separation of two ruthenium atoms defined by Ru(2) … Ru(3), which is bridged by two 3 electron donar oxygen atoms through two-pyridinonato ligands above and below triruthenium plane, and 8 terminal CO groups. Atoms Ru(2) and Ru(3) ligated by two CO ligands each and Ru(1) with four. Antitumor activity of the compounds 1–4 has been evaluated against five types of human cancer cell lines. Compounds 1 and 2 show excellent antitumor activity due to lipophilic nature of N-substituted arene pyridinonato ligands than compounds 3 and 4. Structure-activity studies show that there is a correlation between the N-substituted arene pyridinonato ligands and an increase in activity following the order 1 > 2>3 > 4. The anticancer activity of compounds 1 and 2 is between 1–2 orders of magnitude more active than cisplatin. This is possibly due to substitution of CO ligands at Ru(1) by transferrin delivery vehicle transporting to cancer cells and lipophilic N-substituted arenes diffuse through lipophic membrane leading to apoptosis and other carbonyl groups under physiological conditions likely function as carbonyl releasing molecules (CORMs).

Design, synthesis and docking study of pyridine and thieno[2,3-b] pyridine derivatives as anticancer PIM-1 kinase inhibitors

A series of pyridine and thieno[2,3-b]pyridine derivatives have been designed and synthesized as anticancer PIM-1 kinase inhibitors. Thirty-seven compounds were selected by NCI to be tested initially at a single dose (10 µM) in the full NCI 60 cell line panel. Compound 5b showed potent anticancer activity and was tested twice in the five-dose assay which confirmed its potent antitumor activity (GI50 values 0.302–3.57 µM) against all tested tumor cell lines except six cell lines where they showed moderate sensitivity. This compound was sent to NCI biological evaluation committee and still under consideration for further testing. In addition, the most active anticancer compounds in each series, 5b, 8d, 10c, 13h, and 15e, were evaluated for their PIM-1 kinase inhibitory activity. Compound 8d was the most potent one with IC50 = 0.019 µM followed by 5b, 15e, 10c and 13h with IC50 values 0.044, 0.083, 0.128 and 0.479 µM respectively. Moreover, docking study of the most active compounds in PIM-1 kinase active site was consistent with the in vitro activity.

Abstract 5038: Ready to use 3D spheroid cultures as a standard tool to screen for compounds targeting cancer

Abstract The cancer stem cell (CSC) concept has important implications not only for our understanding of carcinogenesis, but also for the development of cancer therapeutics. There is a growing body of preclinical evidence showing that cancer stem cells contribute to chemotherapy and radiation resistance in breast cancer. The use of drugs that interfere with stem cell self-renewal represents the strategy of choice for novel effective anti-cancer treatments, but also a great challenge because cancer stem cells and their normal counterparts share many pathways. The biology of cancer stem cells has proven complex and difficult to translate into effective therapeutic strategies. The question arises as: how do we test compounds for anti-cancer stem cell activity? The answer is: phenotypic screening. There are indeed several functional assays well validated in the scientific literature that have been used for years associated to the ability of cancer cells to demonstrate stem cell behavior. The most relevant is the 3D tumor spheroid assay. This assay has been used to uncover and culture stem cells from many tissues as well as from tumors. There are multiple reports now that show that spheroid derived cells are enriched in tumor initiating or cancer stem cells, derived from cell lines and from natural fresh tumors as well. Here we describe the use of 3D spheroid models to profile compound activity against cancer stem cells. Furthermore, a case of compounds preventing hypoxia-inducible transcription factor (HIFs) activity is presented. Recently, HIF transcription factor biology has been linked to pathways that regulate stem cell self-renewal and pluripotency, suggesting a new mechanism whereby HIF proteins may drive tumor growth, through the generation of tumour-initiating cells or cancer stem cells. Therefore, targeting the HIF pathway may provide a novel therapeutic avenue to target cancer stem cells. We demonstrate that interfering with HIF pathway activation prevents mammosphere formation, validated through indenpendent confirmation through Sox2 promoter activation, Aldefluor® assay and in vivo proof-of concept experiments targeting tumor initiation. Citation Format: Angel Garcia Martin, Olatz Leis, Juan Gumuzio, Inés Prieto, Estibaliz Ruiz. Ready to use 3D spheroid cultures as a standard tool to screen for compounds targeting cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5038.

Abstract 2681: Antiproliferative effects of the naturally occurring solamargine and related glycoalkaloids against liver cancer cells

Abstract Hepatocellular carcinoma (HCC) is progressively increasing tumor with lack of accurate prognosis and inadequate systemic treatment approaches. Solanum sp. (such as Solanum melongena) is a folk herb which is reported to possess anticancer properties. In a continuity for our interest in pursuing the anticancer activity of compounds isolated from the fruit peels of Solanum melongena, the HPLC profiling and ESI-MS assessment for the methanolic extract evidenced the presence of bioactive glycoalkaloids (solasonine, solasodine and solamargine). These glycoalkaloids were isolated, purified and proved to possess in vitro cytotoxicity against human liver cancer cell lines (Huh7 and HepG2). Herein, we investigated the potential mechanism of action of these compounds using DNA content flow-cytometry and apoptosis/necrosis differential anaylsis using annexin-V/FITC staining. Solasonine, solasodine and solamargine inducd significant antiproliferative effect against liver cancer cells (Huh7 and HepG2) which was attributed to cell cycle arrest at S-phase. Solamargine, solasodine and solasonine induced significant apoptosis in Huh7 cells. Only solamargine-induced cell cycle arrest, was reflected as apoptotic cell killing effect against HepG2 cells. In conclusion, glycoalkaloids derived from Solanum melongena and particularly, solamargine are promising antiproliferative agents with potential anticancer effects. Citation Format: Mostafa I. Fekry, Shahira M. Ezzat, Maha M. Salama, Ahmed M. Al-Abd. Antiproliferative effects of the naturally occurring solamargine and related glycoalkaloids against liver cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2681.

Abstract 2662: Indenoisoquinoline topoisomerase I inhibitors target the DNA G-quadruplex formed in the c-Myc promoter and cause MYC downregulation

Abstract The inhibition of DNA topoisomerase I (Top1) has proven to be a successful approach toward the design of anticancer agents. Indenoisoquinoline derivatives have been designed and developed as Top1 inhibitors and can overcome some shortcomings associated with the camptothecin Top1 inhibitors, resulting in three indenoisoquinoline compounds, indotecan (LMP 400), indimitecan (LMP776), and LMP744 entering Phase I clinical trials at the National Cancer Institute. However, some active indenoisoquinolines did not show potent Top1 inhibition, suggesting a separate mechanism of action. c-Myc is one of the most commonly deregulated genes in human cancers; a DNA G-quadruplex (G4) formed in the proximal promoter region of c-Myc has been found to function as a transcriptional silencer and be amenable to small molecule targeting. As indenoisoquinolines share structure similarity to our c-Myc G-quadruplex (MycG4)-interactive compounds, we hypothesized that indenoisoquinolines could stabilize MycG4 and downregulate MYC transcription. Using a fluorescence resonance energy transfer (FRET) assay, we examined the MycG4 stabilization activity of 56 indenoisoquinoline compounds that we previously developed as Top1 inhibitors. Notably, 26 of the 56 compounds decreased the fluorescence intensity by at least 50%, and the 10 most potent compounds reduced fluorescence intensities by over 70%, indicating that these indenoisoquinolines are effective MycG4 stabilizers. The identified compounds were further characterized by fluorescence anisotropy, circular dichroism, and nuclear magnetic resonance for MycG4 interactions, followed by western blot assays for MYC downregulation. Significantly, the compounds with good MycG4 binding activity and affinity exhibited significant dose-dependent reduction of MYC expression, indicating that targeting the c-Myc promoter G-quadruplex is a likely mechanism of action for these active anticancer compounds. Furthermore, some active indenoisoquinolines exhibited both MYC downregulation and Top1 inhibition, suggesting that dual targeting c-Myc G-quadruplex and Top1 may represent a novel mechanism of action for anticancer drug design. Citation Format: Kaibo Wang, Mohamed S. A. Elsayed, Guanhui Wu, Mark Cushman, Danzhou Yang. Indenoisoquinoline topoisomerase I inhibitors target the DNA G-quadruplex formed in the c-Myc promoter and cause MYC downregulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2662.

The Potential of Neural Stem Cell as Vehicle to Deliver Quercus infectoria Extract to Glioma Cell In Vitro

Glioblastoma multiforme (GBM) is the most malignant subtype of brain cancer. However, current clinical treatments for GBM are limited in effectiveness and often impose additional side effects on patients. Here, we developed targeted anti-cancer therapy (TAT) using neural stem cells (NSC) as delivery agent to transport anti-cancer compounds directly to GBM in vitro. Anti-cancer active compounds: Tannic acid (TA) and gallic acid (GA) were extracted from local medicinal plant - Quercus infectoria (QI) using soxhlet technique with 100% methanol (QI-100%) or 70% methanol (QI-70%) solvent. Concentration of TA and GA measured using HPLC were 72.56 and 43.66 μg/mL in QI-100%, while in QI-70%, the concentrations were 72.41 and 43.31 μg/mL, respectively. Cytotoxicity effects of QI-100% and QI-70% on human GBM cell line (DBTRG-05MG), human NSC line (H9-hNSC) and human normal brain glial cell line (SVG-p12) (as negative control) were determined using MTT assay. Both QI-100% and QI-70% showed anti-proliferative properties against DBTRG-05MG at IC50, but not on H9-hNSC and SVG-p12. Taken together, data indicated that both QI extracts contained TA and GA which exhibit anti-proliferative effect specifically on cancerous cells only. Next, QI-treated H9-hNSC was seeded in a modified Boyden chamber for 12 h to investigate its migration capacity towards DBTRG-05MG. The result showed that H9-hNSC migrated towards DBTRG-05MG with 4-folds higher capacity compared to control. In addition, the migration of QI-100% treated H9-hNSC successfully reduced the number of DBTRG-05MG, indicating the anti-GBM potential of these cells after migration. In conclusion, NSC could be a specific anti-cancer compound delivery agent for GBM, reducing unwanted side effects on patients.

Two mixed-ligand coordination compounds: crystal structure and anti-liver cancer activity

Two 3D mixed-ligand coordination compounds, [Cd(1,3-bdc)(bmip)]n [1, H21,3-bdc = 1,3-benzenedicarboxylic acid, bmip = 1,3-bis(2-methyl-1H-imidazol-1-yl)propane] and [Cd(5-mpc)(bmip)]n (2, H25-mpc = 5-methylisophthalic acid), have been successfully synthesized under hydrothermal conditions and characterized successfully by single crystal X-ray analysis. In addition, in vitro anticancer activities of compounds 1 and 2 on three human liver cancer cells (PLC/PRF/5, BEL-7404 and MHCC97-L) were further determined.

Molecular Targets of Active Anticancer Compounds Derived from Marine Sources.

Over the past decades, a number of novel compounds, which are produced in the marine environment, have been found to exhibit the anticancer effects. This review focuses on molecular targets of marine-derived anticancer candidates in clinical and preclinical studies. They are kinases, transcription factors, histone deacetylase, the ubiquitin-proteasome system, and so on. Specific emphasis of this review paper is to provide information on the optimization of new target compounds for future research and development of anticancer drugs, based on the identification of structures of these target molecules and parallel compounds.

Structural, vibrational and quantum chemical investigations for 6,7-dichloro-2-methyl-5,8-quinolinedione. Cytotoxic and molecular docking studies

6,7-Dichloro-2-methyl-5,8-quinolinedione was investigated using different experimental methods as well as a variety of various quantum chemical calculations in order to characterize its molecular structure as a potential anticancer active compound. We used X-ray diffraction, IR spectrum analysis supplemented by the density functional theory (DFT) calculations, molecular electrostatic potential (MEP) and molecular orbital (HOMO, LUMO) analyses. The analyzes were carried out with respect to 6,7-dichloro-5,8-quinolinedione. It was found that introduction of the methyl group at the C-2 position distinctly affected the crystal structure, formation of H-bonds and the carbonyl stretching IR bands of the title compound. The molecular electrostatic potential map showed how the electrophilic and nucleophilic regions are located in the molecule. The intra- and intermolecular bonding and interaction between bonds were interpreted using the Natural Bond Orbital (NBO) and Natural Localized Molecular Orbital (NLMO) analysis.The title compound was tested for its anticancer activity in vitro against the several human cancer cell lines. 6,7-Dichloro-2-methyl-5,8-quinolinedione showed a higher cytotoxic activity against cancer cell lines containing a higher level of NQO1 enzyme, like melanoma (C-32) and breast (MCF-7) cancer cell lines. The molecular docking was used to examine the probable interaction between the molecule of the tested compound and the NQO1 enzyme. The analysis showed that the 5,8-quinolinedione moiety of the title compound formed a hydrophobic interaction with phenylalanine (Phe 178), tyrosine (Tyr 126 and Tyr 128) and FAD cofactor.

Effects on estrogen-dependent and triple negative breast cancer cells growth of Ni(II), Zn(II) and Cd(II) complexes with the Schiff base derived from pyridine-2-carboxaldehyde and 5,6-diamino-1,3-dimethyluracil explored through the renin-angiotensin system (RAS)-regulating aminopeptidases

A series of Ni(II), Zn(II) and Cd(II) complexes with the Schiff base derived from the condensation 1:1 from pyridine-2-carboxaldehyde and 5,6-diamino-1,3-dimethyluracil (6-amino-1,3-dimethyl-5-[(pyridin-2-ylmethylidene)-amino]pyrimidine-2,4(1H,3H)-dione, DAAUPic) were synthesized and subsequently characterized by means of elemental analysis, FT-IR, NMR and nine of them by X-ray diffraction. Except the [Zn(μ-O,O′-AcO)(N5,N6,N1F-DAAUPicH–1)]2 and [Cd(O,O′-NO3)(μ-O4,(N5,N6,N1F)-DAAUPicH−1)(H2O)]2·2H2O dimers and the [Cd(μ-S,N-SCN)(N5,N6,N1F-DAAUPicH−1)]n chain-like polymer, all of them display monomeric molecular structures. The anticancer activity of compounds was also explored studying their effects on renin-angiotensin system (RAS)-regulating aminopeptidases on estrogen-dependent and triple negative breast cancer cell lines. At the concentrations used, some of the complexes showed different effects on (RAS) peptidases, which support the idea that their effects on cell growth/proliferation could be related to autocrine/paracrine regulatory functions of their corresponding peptide substrates.