Anticancer Activity and High Content Screening of New 6-Substituted-5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazoline Derivatives

2021 ◽  
pp. 2397-2405
Author(s):  
Hiba Ali Hasan ◽  
Afrah Salman ◽  
Abdulmalek Emilia
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Elemental Analysis ◽  
Inhibitory Concentration ◽  
High Content Screening ◽  
Spectroscopic Methods ◽  
High Toxicity ◽  
Anticancer Activities ◽  
Microwave Assisted ◽  
Quinazoline Derivatives

Pursuing our interest in bioactive heterocyclic compound, two benzoimidazoquinazoline derivatives were synthesised using both microwave-assisted and classical heating methods. Structures of the compounds were confirmed by standard spectroscopic methods and elemental analysis. The target scaffolds were incidentally found to emit blue light when exposed to ultraviolet light. Consequently, a photoluminescence characterization was carried out as a part of characterization protocol. The anticancer activities of the benzimidazoquinazoline compounds were investigated using both methylthiazol tetrazolium (MTT) and the high content screen (HCS) assays against liver hepatocellular cells. The results showed a significant reduction in the inhibitory concentration of the cancer cells by 1 and 2.6 fold when exposed to compounds (3a) and (3b), respectively. The high content screen (HCS) was conducted for compound (3b) and the results showed high toxicity towards the cancer cells.

Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

2019 ◽  
Vol 15 (5) ◽  
pp. 550-560
Author(s):  
Mateusz D. Tomczyk ◽  
Anna Byczek-Wyrostek ◽  
Klaudia Strama ◽  
Martyna Wawszków ◽  
Przemysław Kasprzycki ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Topoisomerase Ii ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
Substitution Pattern ◽  
Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

scholarly journals NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Wei-Jan Huang ◽  
Yu-Chih Liang ◽  
Shuang-En Chuang ◽  
Li-Ling Chi ◽  
Chi-Yun Lee ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Xenograft Model ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Cell Cycle Regulators ◽  
Anticancer Activities ◽  
Gene Expressions

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1,p21(Waf1/Cip1)gene expression had markedly increased whilecyclin B1andD1gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor genep53in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activityin vitroandin vivo.

A Novel Cyclic Dinuclear Gold(I) Complex Induces Anticancer Activity via Oxidative Stress-Mediated Intrinsic Apoptotic Pathway in MDA-MB-231 Cancer Cells

2022 ◽  
Author(s):  
Ahmed K. Abogosh ◽  
Meshal Alghanem ◽  
Saeed Ahmad ◽  
Abdullah Alasmari ◽  
Homood M. As Sobeai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Elemental Analysis ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway ◽  
X Ray ◽  
X Ray Crystallography ◽  
Ethyl Amine

A new dinuclear cyclic gold(I) complex [Au2(DCyPA)2](PF6)2, 1 based on bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA) has been synthesized and characterized by elemental analysis, IR and NMR spectroscopies, and X-ray crystallography. In the dinuclear...

scholarly journals Secondary Metabolites from the Culture of the Marine-derived Fungus Paradendryphiella salina PC 362H and Evaluation of the Anticancer Activity of Its Metabolite Hyalodendrin

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 191
Author(s):  
Ambre Dezaire ◽  
Christophe H. Marchand ◽  
Marine Vallet ◽  
Nathalie Ferrand ◽  
Soraya Chaouch ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Crude Extract ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
Cancer Cell Line ◽  
Anticancer Activities ◽  
Chemical Library ◽  
Altered Expression ◽  
Cancer Aggressiveness

High-throughput screening assays have been designed to identify compounds capable of inhibiting phenotypes involved in cancer aggressiveness. However, most studies used commercially available chemical libraries. This prompted us to explore natural products isolated from marine-derived fungi as a new source of molecules. In this study, we established a chemical library from 99 strains corresponding to 45 molecular operational taxonomic units and evaluated their anticancer activity against the MCF7 epithelial cancer cell line and its invasive stem cell-like MCF7-Sh-WISP2 counterpart. We identified the marine fungal Paradendryphiella salina PC 362H strain, isolated from the brown alga Pelvetia caniculata (PC), as one of the most promising fungi which produce active compounds. Further chemical and biological characterizations of the culture of the Paradendryphiella salina PC 362H strain identified (-)-hyalodendrin as the active secondary metabolite responsible for the cytotoxic activity of the crude extract. The antitumor activity of (-)-hyalodendrin was not only limited to the MCF7 cell lines, but also prominent on cancer cells with invasive phenotypes including colorectal cancer cells resistant to chemotherapy. Further investigations showed that treatment of MCF7-Sh-WISP2 cells with (-)-hyalodendrin induced changes in the phosphorylation status of p53 and altered expression of HSP60, HSP70 and PRAS40 proteins. Altogether, our study reveals that this uninvestigated marine fungal crude extract possesses a strong therapeutic potential against tumor cells with aggressive phenotypes and confirms that members of the epidithiodioxopiperazines are interesting fungal toxins with anticancer activities.

Telomere DNA Binding, Cleavage and Anticancer Activity of [Cu(phendione)(Hpyramol)Cl]

2019 ◽  
Vol 13 (2) ◽  
pp. 171-182
Author(s):  
Palanisamy Uma Maheswari ◽  
Renuga Duraisamy ◽  
Murugesan Kanagavel ◽  
Kalimuthusamy Natarajaseenivasan ◽  
Kadhar Mohamed Meera Sheriffa Begum ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Dna Cleavage ◽  
Phenoxyl Radical ◽  
Anticancer Activities ◽  
Redox Active ◽  
G Quadruplex ◽  
Ic50 Values ◽  
Controlled Potential ◽  
Human Telomere

Background:The ligand Hpyramol is a redox active, which on coordination with Cu(II) cleaves DNA without any added reductant. Another ligand phendione is known for its wide application towards anticancer activities. We combined the ligands with CuCl2 to have an intercalation moiety and a redox active ligand in participation towards telomere DNA cleavage and anticancer activity.Objective:In this study, our aim is to interact it with Human telomere DNA and to see their effects on cancer cells.Methods:The complex [Cu(L)(L’)Cl] has interacted with the human telomere DNA sequence (TTAGGG), HTelo20. The HTelo20 was stabilized under both parallel and antiparallel G-quadruplex conformations and the complex [Cu(L)(L’)Cl] has interacted followed by circular dichroism spectroscopy and gel electrophoresis.Results:The parallel G-quadruplex and randomly coiled conformations of HTelo20 were easily cleaved than the anti-parallel G-quadruplex conformation. The nature of DNA cleavage was found to be oxidative rather hydrolytic. The formation of phenoxyl radical species under electrochemical and controlled potential electrolysis conditions by the complex [Cu(L)(L’)Cl] proves the possibility of oxidative nature of DNA cleavage. The comet assay also proves the DNA cleavage induced by the complex [Cu(L)(L’)Cl] inside the nucleus of HeLa cancer cells.Conclusion:The complex [Cu(L)(L’)Cl] was tested for anticancer activity, induced by ROS and DNA cleavage. The IC50 values resulted in nanomolar concentrations with selected cancer cell lines. Relatively the Cu complex shows less toxicity with the normal cell line L132.

scholarly journals Microwave-Assisted Synthesis of 3,5-Dibenzyl-4-amino-1,2,4-triazole and its Diazo Ligand, Metal Complexes Along with Anticancer Activity

2010 ◽  
Vol 7 (4) ◽  
pp. 1571-1577 ◽  
Author(s):  
Anjali Jha ◽  
Y. L. N. Murthy ◽  
G. Durga ◽  
T. T. Sundari
Keyword(s):  
Microwave Irradiation ◽  
Metal Complexes ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Conventional Method ◽  
Ruthenium Complexes ◽  
Microwave Assisted Synthesis ◽  
Microwave Irradiation Method ◽  
Anticancer Activities ◽  
Microwave Assisted

Synthesis of 3,5-dibenzyl-4-amino-1,2,4-triazole was accomplished via a conventional method as well as microwave irradiation method, followed by diazotization and coupling with 2,4-pentanedione. The dinucleating ligand was isolated and complexed with Ni(II), Cu(II) and Ru(III) chlorides. These complexes were screened on Jurkat, Raji & PBMC cell lines for anticancer activity. Ruthenium complexes showed potential anticancer activities.

scholarly journals Compounds Isolated From the Fruits of Xanthium strumarium, Including a New Neo-Lignan, and Their Anticancer Effects

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2098278
Author(s):  
Ye-Liang Wen ◽  
Min-Jing Li ◽  
Zhi-Jian Ye ◽  
Yue-Ming Liang ◽  
Xiao-Qun Wei
Keyword(s):  
Cancer Cells ◽  
Inhibitory Concentration ◽  
Human Cancer ◽  
Xanthium Strumarium ◽  
Spectroscopic Methods ◽  
Addition Compound ◽  
Antiproliferative Effects ◽  
Anticancer Effects ◽  
Hct 116

A new neo-lignan, (7′ S,8 ′R)-4′,5′,9′-trihydroxy-4,6-dimethoxy-5,8′-oxyneolign-7-en-9-al (1), along with 5 known compounds (2-6), were isolated from the fruits of Xanthium strumarium. Their structures were elucidated by extensive spectroscopic methods. All the isolates were evaluated for in vitro cytotoxicities against the human cancer lines HepG2, A549, HCT-116, and SGC-7901. Compounds 1 and 3 showed potent antiproliferative effects against A549 cancer cells with half-maximal inhibitory concentration (IC50) values of 11.2 and 8.3 µM, respectively. In addition, compound 3 exhibited moderate cytotoxicity to SGC-7901 cancer cells, with an IC50 value of 12.9 µM.

Photodynamic Anticancer Activity of CoFe2O4 Nanoparticles Conjugated with Hematoporphyrin

2015 ◽  
Vol 15 (10) ◽  
pp. 7900-7906 ◽  
Author(s):  
Bong Joo Park ◽  
Kyong-Hoon Choi ◽  
Ki Chang Nam ◽  
Jeeeun Min ◽  
Kyu-Dong Lee ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cobalt Ferrite ◽  
Magnetic Core ◽  
Water Soluble ◽  
Anticancer Activities ◽  
Good Biocompatibility

This work reports the synthesis and the characterization of water-soluble and biocompatible photosensitizer (PS)-conjugated magnetic nanoparticles composed of a cobalt ferrite (CoFe2O4) magnetic core coated with a biocompatible hematoporphyrin (HP) shell. The photo-functional cobalt ferrite magnetic nanoparticles (CoFe2O4@HP) were uniform in size, stable against PS leaching, and highly efficient in the photo-generation of cytotoxic singlet oxygen under visible light. With the CoFe2O4@HP, we acquired in vitro MR images of cancer cells (PC-3) and confirmed good biocompatibility of the CoFe2O4@HP in both normal and cancer cells. In addition, we confirmed the potential of the CoFe2O4@HP as an agent for photodynamic therapy (PDT) applications. The photodynamic anticancer activities in 25, 50, and 100 μg/mL of CoFe2O4@HP were measured and found to exceed 99% (99.0, 99.4, and 99.5%) (p <0.002). The photodynamic anticancer activity was 81.8% (p < 0.003). From these results, we suggest that our CoFe2O4@HP can be used safely as a type of photodynamic cancer therapy with potential as a therapeutic agent having good biocompatibility. Moreover, these photo-functional magnetic nanoparticles are highly promising for applications in versatile imaging diagnosis and as a therapy tool in biomedical engineering.

scholarly journals Phenolic Compounds of Catalpa speciosa, Taxus cuspidate, and Magnolia acuminata have Antioxidant and Anticancer Activity

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 412 ◽  
Author(s):  
Hosam Elansary ◽  
Agnieszka Szopa ◽  
Paweł Kubica ◽  
Fahed A. Al-Mana ◽  
Eman Mahmoud ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Phenolic Acids ◽  
High Performance ◽  
Protocatechuic Acid ◽  
Antioxidant Activities ◽  
Tree Bark ◽  
Anticancer Activities ◽  
Induced Apoptosis

Tree bark represents an important source of medicinal compounds that may be useful for cancer therapy. In the current study, high-performance liquid chromatography with diode-array detection (HPLC-DAD) was used to determine the profile of the phenolic compounds of Catalpa speciosa, Taxus cuspidata, and Magnolia acuminata bark extracts. The antioxidant and anticancer bioactivities against different cancer cell lines were investigated. M. acuminata exerted significantly higher antioxidant activities in the diphenyl picrylhydrazine and β-carotene-linoleic acid assays than the other species. In C. speciosa, novel profiles of phenolic acids (ferulic acid was the predominant compound) and catechin were detected. In T. cuspidata, six phenolic acids were detected; the predominant compounds were hydroxycaffeic acid and protocatechuic acid. In M. acuminata, two phenolic acids and three catechins were detected; catechin was the predominant compound. The three species exerted clear anticancer activity against MCF-7, HeLa, Jurkat, T24, and HT-29 cells, with the strongest activity found in the extracts from M. acuminata. No antiproliferative activity against normal cells was found. Flow cytometry revealed greater accumulation of necrotic and early/late apoptotic cells in various treated cancer cells than in untreated control cells, and protocatechuic acid induced a similar accumulation of necrotic cells to that of the bark extracts. Caspase-3 and -7 activity was increased in cancer cells treated with different bark extracts; the highest activity was found in the M. acuminata treatment. Our results suggested that the treatment of cancer cells with bark extracts of M. acuminata, C. speciosa, and T. cuspidata, and protocatechuic acid induced apoptosis, suggesting an association between anticancer activities and individual phenolic compounds.

scholarly journals Anticancer Activities of Sesewanua Leaf Extracts (Clerodendrum fragrans (Vent.) Willd) Against A549 Lung Cancer Cell

2021 ◽  
Vol 9 (A) ◽  
pp. 1226-1230
Author(s):  
Elisabeth Natalia Barung ◽  
Donald Emilio Kalonio ◽  
Yos Banne ◽  
Norma Tiku Kambuno
Keyword(s):  
Lung Cancer ◽  
Ethyl Acetate ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Ethyl Acetate Fraction ◽  
Water Soluble ◽  
Lung Cancer Cells ◽  
Assay Method ◽  
Anticancer Activities ◽  
A549 Lung

BACKGROUND: Cancer is one of the leading causes of non-communicable diseases in the world, with about 10 million deaths worldwide in 2020. Lung cancer was the most common type of cancer and the highest cause of death. Therapy for lung cancer can be either conventional therapy or molecular targeted therapy that has many limitations. AIM: It is, therefore, important to explore new sources of anticancer activity, including those from plants. One plant that is thought to have anticancer activity is Sesewanua (Clerodendrum fragrans [Vent.] Willd. Syn. Clerodendrum chinense [Osbeck] Mabb., Family Lamiaceae). METHODS: This research is a laboratory experiment. The sample used is the C. fragrans leaves obtained in Malalayang I Timur Village, Malalayang District, Manado City, North Sulawesi Province, while the subjects in this study were A549 lung cancer cells from Cell-Culture Laboratory, Faculty of Pharmacy, Universitas Padjadjaran Bandung. Anticancer activity test was using the MTT tetrazolium assay method. Data in the form of a percentage (%) inhibition of cell proliferation, then determined the value the concentration of 50% proliferation inhibition (IC50) using a computer program online. RESULTS: The results showed that ethanol extract, hexane fraction, ethyl acetate fraction, and water-soluble fraction of C. fragrans had anticancer activity on A549 lung cancer cells. The smallest IC50 value is indicated by ethyl acetate fraction (191, 165 ppm), which is categorized as moderately active.

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