☆ 4.5 Article

Inhibition of human DNA topoisomerase IIα by two novel ellipticine derivatives

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2016)

Get Full Text
Add to Collection

Journal

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 26, Issue 7, Pages 1809-1812

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2016.02.034

Keywords

Ellipticine derivatives; DNA topoisomerase II alpha; Anticancer drugs; Catalytic inhibitor; DNA cleavage; DNA intercalation

Categories

Chemistry, Medicinal Chemistry, Organic

Funding

  1. National Institutes of Health [GM033944, R25-GM062459, T32-GM08320]
  2. Turkish Scientific and Technical Research Assembly [115Z349]

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an antineoplastic agent that intercalates into DNA and alters topoisomerase II activity. Unfortunately, this compound displays a number of adverse properties. Therefore, to investigate new ellipticine-based compounds for their potential as topoisomerase II-targeted drugs, we synthesized two novel derivatives, N-methyl-5-demethyl ellipticine (ET1) and 2-methyl-N-methyl-5-demethyl ellipticinium iodide (ET-2). As determined by DNA decatenation and cleavage assays, ET-1 and ET-2 act as catalytic inhibitors of human topoisomerase II alpha and are both more potent than the parent compound. Neither compound impairs the ability of the type II enzyme to bind its DNA substrate. Finally, the potency of ET-1 and ET-2 as catalytic inhibitors of topoisomerase II alpha appears to be related to their ability to intercalate into the double helix. (C) 2016 Elsevier Ltd. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Chemistry, Physical

Green synthesis, X-ray crystallography, DFT and Hirshfeld analysis of C-2 symmetric 1,3-bis(4-ethylphenyl)triaz-1-ene

Aamer Saeed, Hafiza Zara Tariq, Ghulam Shabir, Tuncer Hokelek, Michael Bolte, Syeda Abida Ejaz, Aftab Ahmed

Summary: A green synthesis method was used to successfully synthesize the novel symmetrical molecule 1,3-bis(4-ethylphenyl)triazene (3) via the self-coupling of 4-ethylaniline in water at room temperature. The structure of 3 was determined using spectroscopic data, elemental analysis, and single crystal X-ray crystallography. The crystal structure of 3 was found to be stabilized by intermolecular hydrogen bonds and van der Waals interactions. The evaluation of the energy frameworks indicated that dispersion energy played a dominant role in the stabilization of the crystal packing. The HOMO and LUMO energies were determined to be -0.19401 and -0.5546, respectively. (C) 2022 Elsevier B.V. All rights reserved.

JOURNAL OF MOLECULAR STRUCTURE (2023)

Add to Collection
Article Chemistry, Multidisciplinary

Phosphorus-nitrogen compounds: part 68. Synthesis, characterization, stereogenism, photophysical and bioactivity studies of novel unsymmetrical dispiro(N/N)cyclotriphosphazenes with carbazolyl and 4-chlorobenzyl pendant arms

Resit Cemaloglu, Nuran Asmafiliz, Zeynel Kilic, Bunyemin Cosut, Busra Nur Sabah, Leyla Acik, Nebahat Aytuna Cerci, Tuncer Hokelek

Summary: This study synthesized organic-inorganic hybrid multi-heterocyclic unsymmetrical cis/trans dispirocyclotriphosphazenes with different pendant arms and investigated their spectral, stereogenic, photophysical, and bioactivity properties.

NEW JOURNAL OF CHEMISTRY (2023)

Add to Collection
Article Chemistry, Physical

Synthesis, single crystal structure determinations, Hirshfeld surface analysis, crystal voids, interaction energies, and density functional theory studies of functionalized 1,3-thiazoles

Hamid Aziz, Aamer Saeed, C. John McAdam, Jim Simpson, Tuncer Hokelek, Erum Jabeen, Asma Khurshid, Muhammad Saleem, Hesham R. El-Seedi

Summary: The current research focuses on the synthesis, crystal structure determination, Hirshfeld surface analysis, interaction energies, and density functional theory calculations of functionalized 1,3-thiazoles (5a and 5b). The synthesized compounds crystallized in monoclinic crystal systems with the P 2 1 /c space group. Intermolecular interactions were analyzed using Hirshfeld surface analysis. The study also investigated the energy contributions, redox behavior, and electrophilic characteristics of the compounds (5a and 5b).

JOURNAL OF MOLECULAR STRUCTURE (2023)

Add to Collection
Article Chemistry, Physical

4-(3-oxo-1,3-dihydroisobenzofuran-1-yl)aminobenzoic acid and its complexes: Synthesis, crystal structures, theoretical calculations and in vitro and in silico antibacterial properties

Azer Ozen, Elif Ozturkkan, Guventurk Ugurlu, Giray Bugra Akbaba, Mustafa Sertcelik, Tuncer Hokelek, Hacali Necefoglu

Summary: The current study synthesized a new ligand and its cobalt and nickel complexes. Their structures were determined using various spectroscopic techniques and X-ray diffraction. The crystal structures revealed the formation of three-dimensional architectures through hydrogen bonding and π-π interactions. The synthesized compounds showed significant antibacterial effects on K. pneumoniae bacteria.

JOURNAL OF MOLECULAR STRUCTURE (2023)

Add to Collection
Article Chemistry, Physical

Syntheses of tetrachloro and tetraamino(2-furanylmethyl)spiro(N/N) cyclotriphosphazenes: Chemical, structural elucidation, antiproliferative and antimigratory activity studies

Huseyin Akbas, Aysegul Senocak, Zeynel Kilic, Secil Erden Tayhan, Sema Bilgin, Asli Yildirim, Tuncer Hokelek

Summary: Schiff bases prepared from condensation reactions of furfural with N-ethyl-1,2-diaminoethane and N-methyl-1,3-diaminopropane were successfully reduced to obtain the starting diamines. Regioselective formation of tetrachloro(2-furanylmethyl)spiro-(N/N)cyclotriphosphazenes was achieved when reacting hexachlorocyclotriphosphazene with the diamines. Furthermore, the Cl replacement reactions with pyrrolidine and piperidine resulted in the synthesis of tetrapyrrolidino and tetrapiperidino cyclotriphosphazenes. The compounds exhibited varying degrees of success in inhibiting the growth and migration of various cancer cells, with the most effective phosphazene derivatives being the five-membered N-ethyl phosphazenes (3a and 3b).

JOURNAL OF MOLECULAR STRUCTURE (2023)

Add to Collection
Article Chemistry, Physical

Synthesis, single crystal X-ray structure determination, Hirshfeld surface analysis, interaction energies, and density functional theory calculations of N,N′-(cyclohexane-1,4-dicarbonothioyl)bis(4-methylbenzamide)

Hamid Aziz, Aamer Saeed, Jim Simpson, Tuncer Hokelek, Erum Jabeen

Summary: The research focuses on the convenient synthesis, molecular and crystal structures of C-2 symmetric N,N'-(cyclohexane-1,4-dicarbonothioyl)bis(4-methylbenzamide). The crystal structure exhibits three-dimensional architecture with hydrogen bonding and van der Waals contacts as the dominant interactions. Analysis of the crystal voids suggests the absence of any large cavity in the crystal. The optimized molecular structure and molecular electrostatic potential surface provide insights into the nucleophilic and electrophilic behavior of the bis-amide.

JOURNAL OF MOLECULAR STRUCTURE (2023)

Add to Collection
Article Chemistry, Physical

Synthesis, Crystal Structure, Hirshfeld Surface Analysis, DNA/BSA Interaction and Molecular Docking Studies of 2-(6-(4-chlorophenyl)-1,2,4-triazin-3-yl)quinoline

Tolga Gokturk, Talip Zengin, Tuncer Hokelek, Cansu Gokce Topkaya, Ramazan Gup

Summary: In this study, a novel 1,2,4-triazine derivative, 2-(6-(4-chlorophenyl)-1,2,4-triazin-3-yl)quinoline, was synthesized and characterized by various analytical techniques. The molecular and crystal structures were determined using X-ray crystallography, revealing the involvement of hydrogen bonding and van der Waals interactions in the crystal packing. The compound exhibited binding activity with CT-DNA via the minor groove and with BSA via subdomain IIIB.

JOURNAL OF MOLECULAR STRUCTURE (2023)

Add to Collection
Article Chemistry, Multidisciplinary

Synthesis, Structural Investigations, DNA/BSA Interactions, Molecular Docking Studies, and Anticancer Activity of a New 1,4-Disubstituted 1,2,3-Triazole Derivative

Tolga Gokturk, Esin Sakalli Cetin, Tuncer Hokelek, Hanife Pekel, Ozge Sensoy, Ebru Nur Aksu, Ramazan Gup

Summary: A new 1,2,3-triazole derivative was synthesized and its structure was analyzed using multiple techniques. The compound exhibited significant DNA and protein binding activity both in vitro and in vivo, and showed high cytotoxicity against Caco-2 cancer cell lines, possibly by inducing apoptosis.

ACS OMEGA (2023)

Add to Collection
Article Crystallography

Crystal structure and Hirshfeld surface analysis of 3-ethoxy-1-ethyl-6-nitroquinoxalin-2(1H)-one

Seqqat Yousra, Lhoussaine El Ghayati, Tuncer Hokelek, Fouad Ouazzani Chahdi, Joel T. Mague, Youssef Kandri Rodi, Nada Kheira Sebbar

Summary: The title compound exhibits two molecules with slightly different conformations in the crystal, which are connected by hydrogen bonds and stacking interactions. Hirshfeld surface analysis reveals that H···H and H···O/O···H interactions are the major contributions to the crystal packing. The density functional theory calculations agree well with the experimental results.

ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS (2023)

Add to Collection
Article Crystallography

Crystal structure, Hirshfeld surface and crystal void analysis, intermolecular interaction energies, DFT calculations and energy frameworks of 2H-benzo[b][1,4]thiazin-3(4H)-one 1,1-dioxide

Ezaddine Irrou, Younesse Ait Elmachkouri, Ahmed Mazzah, Tuncer Hokelek, Amal Haoudi, Joel T. Mague, Mohamed Labd Taha, Nada Kheira Sebbar

Summary: The crystal structure and energy characteristics of a molecule containing a nitrogen-sulfur heterocyclic structure were studied, and hydrogen bonding and π-π interactions were found in the crystal. The crystal packing was analyzed through experimental and theoretical calculations.

ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS (2023)

Add to Collection
Article Crystallography

Synthesis, crystal structure and Hirshfeld surface analysis of 1-(12-bromododecyl)indoline-2,3-dione

Nohaila Rharmili, Omar Abdellaoui, Amal Haoudi, Joel T. Mague, Tuncer Hokelek, Fouad Ouazzani Chahdi, Youssef Kandri Rodi, Ahmed Mazzah, Nada Kheira Sebbar

Summary: The title compound possesses an almost planar indoline portion and an all-trans conformation for the 12-bromododecyl chain, except for the gauche terminal C-C-C-Br fragment. The crystal structure forms a micellar-like structure through C-H center dot center dot center dot O hydrogen bonds and pi-stacking interactions between the indolinedione head groups and intercalation of the 12-bromododecyl tails. The most important contributions for crystal packing come from H...H (58.9%), H center dot center dot center dot O/O center dot center dot center dot H (17.9%), and H center dot center dot center dot Br/Br center dot center dot center dot H (9.5%) contacts, as indicated by Hirshfeld surface analysis. A density functional theory (DFT) optimized structure at the B3LYP/6-311 G(d,p) level agrees well with the experimentally determined molecular structure in the solid state.

ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS (2023)

Add to Collection
Article Crystallography

Crystal structure, Hirshfeld surface analysis, interaction energy and energy framework calculations, as well as density functional theory (DFT) computation, of methyl 2-oxo-1-(prop-2-ynyl)-1,2-dihydroquinoline-4-carboxylate

Ayoub El-Mrabet, Amal Haoudi, Samira Dalbouha, Mohamed Khalid Skalli, Tuncer Hokelek, Frederic Capet, Youssef Kandri Rodi, Ahmed Mazzah, Nada Kheira Sebbar

Summary: The research investigates the difference between the crystal structure and the molecular structure of a molecule, and explains the crystal packing through the analysis of contributions from different interactions. In addition, the energy gap is determined by analyzing the HOMO-LUMO behavior.

ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS (2023)

Add to Collection
Article Chemistry, Multidisciplinary

Phosphorus-nitrogen compounds: part 71. Novel unsymmetrically-substituted dispiro-cyclotriphosphazenes: synthesis, characterization, antituberculosis activity, and phototunable charge storage studies

Resit Cemaloglu, Ipek Berberoglu, Mehtap Yakut, Arzu Binici, Nuran Asmafiliz, Zeynel Kilic, Remziye Guzel, Gulbahar Erdal, Hulya Simsek, Tuncer Hokelek

Summary: The aim of this research is to synthesize and characterize new organic-inorganic hybrid multi-heterocyclic dichlorodispiro(N/N)cyclotriphosphazenes and to elucidate their antituberculosis activities. The characterization of the new phosphazenes was carried out using various spectroscopic techniques and elemental analysis, and the molecular and crystal structures were determined using single-crystal X-ray crystallography. Among the synthesized compounds, trans-6a showed the highest antituberculosis activity.

NEW JOURNAL OF CHEMISTRY (2023)

Add to Collection
Article Chemistry, Physical

A new 1,2,4-triazine-n-oxide compound: Synthesis, crystal structure, Hirshfeld surface analysis and supercapacitor applications

Cansu Gokce Topkaya, Sema Aslan, Tolga Goturk, Sultan Kincal, Tuncer Hokelek, Ramazan Gup

Summary: This paper reports a metal catalyst-free synthesis method for the one-step synthesis of 6-(4-chlorophenyl)-3,3-dimethyl-4-(Noxide)-1,2,3,4-tetrahydro-1,2,4-triazine. The compound's molecular and crystal structures were characterized, and various interactions were identified in the crystal packing. Additionally, the electrochemical characterizations and supercapacitor performances of the compound were investigated.

JOURNAL OF MOLECULAR STRUCTURE (2024)

Add to Collection
Article Chemistry, Multidisciplinary

Synthesis, Structural Investigations, DNA/BSA Interactions, Molecular Docking Studies, and Anticancer Activity of a New 1,4-Disubstituted 1,2,3-Triazole Derivative

Tolga Gokturk, Esin Sakalli Cetin, Tuncer Hokelek, Hanife Pekel, Ozge Sensoy, Ebru Nur Aksu, Ramazan Gup

Summary: In this study, a new 1,2,3-triazole derivative was synthesized and its structure was characterized using various analysis techniques. The compound exhibited hydrogen bonding and van der Waals interactions in the crystal packing, and demonstrated binding activity to DNA and bovine serum albumin. Furthermore, the compound showed significant anticancer activity and induced apoptosis in Caco-2 cells.

ACS OMEGA (2023)

Add to Collection
Article Chemistry, Medicinal

Design and synthesis of a library of C2-substituted sulfamidoadenosines to probe bacterial permeability

Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan

Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

Add to Collection
Article Chemistry, Medicinal

Design of MERS-CoV entry inhibitory short peptides based on helix-stabilizing strategies

Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang

Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

Add to Collection
Article Chemistry, Medicinal

Development of novel β2-adrenergic receptor agonists for the stimulation of glucose uptake - The importance of chirality and ring size of cyclic amines

Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman

Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

Add to Collection
Article Chemistry, Medicinal

Conformationally constrained potent inhibitors for enhancer of zeste homolog 2 (EZH2)

Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li

Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

Add to Collection
Article Chemistry, Medicinal

The potential of Rhein's aromatic amines for Parkinson's disease prevention and treatment: α-Synuclein aggregation inhibition and disaggregation of preformed fibers

Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang

Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

Add to Collection
Article Chemistry, Medicinal

Design, synthesis and biological evaluation of novel cationic liposomes loaded with melphalan for the treatment of cancer

Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla

Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

Add to Collection
Webinars Posters Questions Hubs Funding Journals Papers Connect Collections Reviewers About Us FAQs Mobile App Privacy Policy Terms of Use
© Peeref 2019-2024. All rights reserved.