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https://www.readbyqxmd.com/read/28531811/synthesis-of-novel-indole-derivatives-as-promising-dna-binding-agents-and-evaluation-of-antitumor-and-antitopoisomerase-i-activities
#1
Elizabeth Almeida Lafayette, Sinara Mônica Vitalino de Almeida, Renata Virginia Cavalcanti Santos, Jamerson Ferreira de Oliveira, Cezar Augusto da Cruz Amorim, Rosali Maria Ferreira da Silva, Maira Galdino da Rocha Pitta, Ivan da Rocha Pitta, Ricardo Olimpio de Moura, Luiz Bezerra de Carvalho Júnior, Moacyr Jesus Barreto de Melo Rêgo, Maria do Carmo Alves de Lima
Molecules bearing indole nucleus present diverse biological properties such as antitumor and anti-inflammatory activities that can be associated both to DNA and protein interactions. This study focused on the synthesis of new indole derivatives with thiazolidines and imidazolidine rings condensed as side chains as well as the evaluation of their ability to interact with the DNA and antitumor and topoisomerase inhibition activities. All derivatives were successfully synthesized and their structures were elucidated by mass spectrometry (MS), infrared (IR), spectroscopy (1)H NMR, (13)C NMR, COSY (1)H-(1)H and HSQC (1)H-(13)C...
May 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28529554/novel-drugs-in-pediatric-gliomas
#2
Dongli Zhang, Xiaoming Liu, Conghai Fan, Jiao Chen
Astrocytomas (gliomas) are the most common primary brain tumors among adults and second most frequent neoplasm among children. New ideas and novel approaches are being explored world over with aim to devise better management strategeies for this deadly pathological state. We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting importance of various therapeutic drugs against gliomas. It was observed clearly that this approach of using therapeutic drugs is clearly evolving and has been observed to be promising future therapeutic avenue against gliomas...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528358/dna-topoisomerase-targeting-chemotherapeutics-what-s-new
#3
REVIEW
Selma M Cuya, Mary-Ann Bjornsti, Robert C A M van Waardenburg
To resolve the topological problems that threaten the function and structural integrity of nuclear and mitochondrial genomes and RNA molecules, human cells encode six different DNA topoisomerases including type IB enzymes (TOP1 and TOP1mt), type IIA enzymes (TOP2α and TOP2β) and type IA enzymes (TOP3α and TOP3β). DNA entanglements and the supercoiling of DNA molecules are regulated by topoisomerases through the introduction of transient enzyme-linked DNA breaks. The covalent topoisomerase-DNA complexes are the cellular targets of a diverse group of cancer chemotherapeutics, which reversibly stabilize these reaction intermediates...
May 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28527284/-new-multiplex-pcr-for-species-specific-diagnosis-of-human-candidiasis
#4
Liliana Torcoroma García, Liany Johanna Luna, Tania Katherine Velasco, Beatriz Elena Guerra
INTRODUCTION: Candidiases is a group of opportunistic infections caused by yeasts belonging to the genus Candida. Candida albicans is the most prevalent species in both superficial and deep infections, however, the clinical importance of non-albicans Candida has increased during the last decade, driving an urgent need for diagnostic tests that allow for species-level resolution and selection of the optimum therapeutic approach. OBJECTIVE: To design and to optimize a new multiplex PCR assay for the simultaneous identification of the five most relevant species of Candida involved in human candidiasis etiology...
June 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526868/chitosan-dextran-sulfate-coated-doxorubicin-loaded-plga-pva-nanoparticles-caused-apoptosis-in-doxorubicin-resistance-breast-cancer-cells-through-induction-of-dna-damage
#5
Sumit Siddharth, Anmada Nayak, Deepika Nayak, Birendra Kumar Bindhani, Chanakya Nath Kundu
To overcome the toxicity, pharmacokinetics and drug resistance associated with doxorubicin (DOX), a strategy was developed by encapsulating DOX- loaded-PLGA-PVA- nanoparticles within chitosan-dextran sulfate nanoparticles (CS-DS) [CS-DS-coated-DOX-loaded -PLGA-PVA-NP] and study the sensitivity against DOX- resistance- breast cancer cells (MCF-7-DOX-R). These CS-DS and PLGA-PVA double coated DOX are spherical, stable, polydispersed and have zeta potential +2.89 mV. MCF-7- DOX-R cells were derived by exposing increasing doses of DOX in MCF-7 cells...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28525845/novel-amidino-substituted-benzimidazole-and-benzothiazole-benzo-b-thieno-2-carboxamides-exert-strong-antiproliferative-and-dna-binding-properties
#6
Maja Cindrić, Samy Jambon, Anja Harej, Sabine Depauw, Marie-Hélène David-Cordonnier, Sandra Kraljević Pavelić, Grace Karminski-Zamola, Marijana Hranjec
Within this manuscript design, synthesis of novel 2-imidazolinyl substituted benzo[b]thieno-2-carboxamides bearing either benzimidazole or benzothiazole subunit and biological activity are presented and described. The antiproliferative activities were assessed in vitro on a panel of human cancer cell lines. Tested compounds showed moderate activity while cytotoxicity on normal fibroblasts was lower in comparison with 5-fluorouracile. The variations of 2-imidazolinyl substituent at heteroaromatic subunits in different positions led to different cytotoxic properties...
May 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28520501/molecular-characterization-of-multidrug-resistant-escherichia-coli-isolates-from-bovine-clinical-mastitis-and-pigs-in-the-vojvodina-province-serbia
#7
Dalibor Todorović, Maja Velhner, Edita Grego, Dejan Vidanović, Dubravka Milanov, Dejan Krnjaić, Corinna Kehrenberg
The aim of the study was to characterize multidrug-resistant (MDR) Escherichia coli isolates collected in Serbia from bovine clinical mastitis cases and diseased pigs, mainly with molecular methods. A total of 48 E. coli isolates was collected during the years 2013-2014, of which 22 were MDR and were included in further analysis. Phylogenetic typing showed that 17 isolates belonged to group A, while two isolates were classified in group B1 and a single one in group D. All isolates showed unique macrorestriction patterns...
May 18, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28513176/selective-inhibition-of-e-coli-rna-and-dna-topoisomerase-i-by-hoechst-33258-derived-mono-and-bisbenzimidazoles
#8
Nihar Ranjan, Sandra Story, Geraldine Fulcrand, Fenfei Leng, Muzammil Ahmad, Ada King, Souvik Sur, Weidong Wang, Yuk-Ching Tse-Dinh, Dev Priya Arya
A series of Hoechst 33258 based mono and bisbenzimidazoles have been synthesized and their E. coli DNA topoisomerase I inhibition, binding to B-DNA duplex and antibacterial activity has been evaluated. Bisbenzimidazoles with alkynyl side chains display excellent E. coli DNA topoisomerase I inhibition properties with IC50 values < 5.0 μM. Several bisbenzimidazoles (3, 6, 7, 8) also inhibit RNA topoisomerase activity of E. coli DNA topoisomerase I. Bisbenzimidazoles inhibit antibacterial growth much better than mono-benzimidazoles for gram positive strains...
May 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28511910/synthesis-and-biological-research-of-novel-azaacridine-derivatives-as-potent-dna-binding-ligands-and-topoisomerase-ii-inhibitors
#9
Dan Li, Zigao Yuan, Shaopeng Chen, Cunlong Zhang, Lu Song, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
DNA and DNA-related enzymes are one of the most effective and common used intracellular anticancer targets in clinic and laboratory studies, however, most of DNA-targeting drugs suffered from toxic side effects. Development of new molecules with good antitumor activity and low side effects is important. Based on computer aided design and our previous studies, a series of novel azaacridine derivatives were synthesized as DNA and topoisomerases binding agents, among which compound 9 displayed the best antiproliferative activity with an IC50 value of 0...
May 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28511613/antimicrobial-activity-and-molecular-docking-studies-of-a-novel-anthraquinone-from-a-marine-derived-fungus-aspergillus-versicolor
#10
Weiyi Wang, Ruixuan Chen, Zhuhua Luo, Wei Wang, Jianming Chen
A novel anthraquinone, 2-(dimethoxymethyl)-1-hydroxyanthracene-9,10-dione (1), together with nine known compounds (2-10), were isolated from the fermentation of Aspergillus versicolor derived from deep sea sediment. Their structures were established through spectroscopic methods. Compound 1 exhibited strong inhibitory activities against MRSA ATCC 43300 and MRSA CGMCC 1.12409 (with MIC values of 3.9 and 7.8 μg/mL respectively) and moderate activities against tested strains of Vibrio (with MIC values ranging from 15...
May 16, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28510224/dna-supercoiling-is-a-fundamental-regulatory-principle-in-the-control-of-bacterial-gene-expression
#11
REVIEW
Charles J Dorman, Matthew J Dorman
Although it has become routine to consider DNA in terms of its role as a carrier of genetic information, it is also an important contributor to the control of gene expression. This regulatory principle arises from its structural properties. DNA is maintained in an underwound state in most bacterial cells and this has important implications both for DNA storage in the nucleoid and for the expression of genetic information. Underwinding of the DNA through reduction in its linking number potentially imparts energy to the duplex that is available to drive DNA transactions, such as transcription, replication and recombination...
September 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28510219/the-dynamic-interplay-between-dna-topoisomerases-and-dna-topology
#12
REVIEW
Yeonee Seol, Keir C Neuman
Topological properties of DNA influence its structure and biochemical interactions. Within the cell, DNA topology is constantly in flux. Transcription and other essential processes, including DNA replication and repair, not only alter the topology of the genome but also introduce additional complications associated with DNA knotting and catenation. These topological perturbations are counteracted by the action of topoisomerases, a specialized class of highly conserved and essential enzymes that actively regulate the topological state of the genome...
November 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28510216/dna-supercoiling-is-a-fundamental-regulatory-principle-in-the-control-of-bacterial-gene-expression
#13
REVIEW
Charles J Dorman, Matthew J Dorman
Although it has become routine to consider DNA in terms of its role as a carrier of genetic information, it is also an important contributor to the control of gene expression. This regulatory principle arises from its structural properties. DNA is maintained in an underwound state in most bacterial cells and this has important implications both for DNA storage in the nucleoid and for the expression of genetic information. Underwinding of the DNA through reduction in its linking number potentially imparts energy to the duplex that is available to drive DNA transactions, such as transcription, replication and recombination...
November 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28510215/species-specific-supercoil-dynamics-of-the-bacterial-nucleoid
#14
N Patrick Higgins
Bacteria organize DNA into self-adherent conglomerates called nucleoids that are replicated, transcribed, and partitioned within the cytoplasm during growth and cell division. Three classes of proteins help condense nucleoids: (1) DNA gyrase generates diffusible negative supercoils that help compact DNA into a dynamic interwound and multiply branched structure; (2) RNA polymerase and abundant small basic nucleoid-associated proteins (NAPs) create constrained supercoils by binding, bending, and forming cooperative protein-DNA complexes; (3) a multi-protein DNA condensin organizes chromosome structure to assist sister chromosome segregation after replication...
November 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28508041/mitochondrial-protein-linked-dna-breaks-perturb-mitochondrial-gene-transcription-and-trigger-free-radical-induced-dna-damage
#15
Shih-Chieh Chiang, Martin Meagher, Nick Kassouf, Majid Hafezparast, Peter J McKinnon, Rachel Haywood, Sherif F El-Khamisy
Breakage of one strand of DNA is the most common form of DNA damage. Most damaged DNA termini require end-processing in preparation for ligation. The importance of this step is highlighted by the association of defects in the 3'-end processing enzyme tyrosyl DNA phosphodiesterase 1 (TDP1) and neurodegeneration and by the cytotoxic induction of protein-linked DNA breaks (PDBs) and oxidized nucleic acid intermediates during chemotherapy and radiotherapy. Although much is known about the repair of PDBs in the nucleus, little is known about this process in the mitochondria...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28507124/thiophene-antibacterials-that-allosterically-stabilize-dna-cleavage-complexes-with-dna-gyrase
#16
Pan F Chan, Thomas Germe, Benjamin D Bax, Jianzhong Huang, Reema K Thalji, Eric Bacqué, Anna Checchia, Dongzhao Chen, Haifeng Cui, Xiao Ding, Karen Ingraham, Lynn McCloskey, Kaushik Raha, Velupillai Srikannathasan, Anthony Maxwell, Robert A Stavenger
A paucity of novel acting antibacterials is in development to treat the rising threat of antimicrobial resistance, particularly in Gram-negative hospital pathogens, which has led to renewed efforts in antibiotic drug discovery. Fluoroquinolones are broad-spectrum antibacterials that target DNA gyrase by stabilizing DNA-cleavage complexes, but their clinical utility has been compromised by resistance. We have identified a class of antibacterial thiophenes that target DNA gyrase with a unique mechanism of action and have activity against a range of bacterial pathogens, including strains resistant to fluoroquinolones...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28507113/efficacy-of-a-binuclear-cyclopalladated-compound-therapy-for-cutaneous-leishmaniasis-in-the-murine-model-of-infection-with-leishmania-amazonensis-and-its-inhibitory-effect-on-topoisomerase-1b
#17
Angela Maria Arenas Velásquez, Willian Campos Ribeiro, Vutey Venn, Silvia Castelli, Mariana Santoro, Renata Pires de Assis, Rodrigo Alves de Souza, Aline Rimoldi Ribeiro, Thaís Gaban Passalaqua, João Aristeu da Rosa, Amanda Martins Baviera, Antonio Eduardo Mauro, Alessandro Desideri, Elmo Eduardo Almeida-Amaral, Marcia A S Graminha
Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. Here we report the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N' -dimethylbenzylamine (Hdmba) against Leishmania amazonensis...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28506909/the-selective-effect-of-glycyrrhizin-and-glycyrrhetinic-acid-on-topoisomerase-ii%C3%AE-and-apoptosis-in-combination-with-etoposide-on-triple-negative-breast-cancer-mda-mb-231-cells
#18
Yun Cai, Boxin Zhao, Qianying Liang, Yunqi Zhang, Jieying Cai, Guofeng Li
Triple negative breast cancer(TNBC) has generated growing interests due to its aggressive biologic behavior and absence of targeted therapy approach. Glycyrrhizin(GL) from licorice root and its metabolite, glycyrrhetinic acid(GA) have shown extensive bioactivities in clinic. Here, we demonstrate that GL and GA have contrary anti-cancer effect on TNBC MDA-MB-231 cells. Beside its inhibition of cell proliferation, GA at non-cytotoxic concentration showed synergistic effect in combination with anti-cancer drug, etoposide(VP-16)...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28506627/rxrb-is-a-mhc-encoded-susceptibility-gene-associated-with-anti-topoisomerase-i-antibody-positive-systemic-sclerosis
#19
Akira Oka, Yoshihide Asano, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Masataka Kuwana, Yasushi Kawaguchi, Toshiyuki Yamamoto, Hiroki Takahashi, Daisuke Goto, Hirahito Endo, Masatoshi Jinnin, Shuhei Mano, Kazuyoshi Hosomichi, Tomotaka Mabuchi, Mahoko Takahashi Ueda, So Nakagawa, Stephan Beck, Seiamak Bahram, Kazuhiko Takehara, Shinichi Sato, Hironobu Ihn
Systemic sclerosis (SSc) is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen (HLA) locus. However, the functional relationship between HLA gene(s) and disease development remains unknown. To elucidate major histocompatibility complex (MHC)-linked SSc genetics, we performed genotyping of MHC-borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti-topoisomerase I antibody-positive patients and 561 healthy controls, all of Japanese descent. Those results revealed 2 MHC haplotypes associated with SSc...
May 12, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28506425/fluoroquinolone-resistance-in-streptococcus-pneumoniae-isolates-in-germany-from-2004-2005-to-2014-2015
#20
Julia Schmitz, Mark van der Linden, Adnan Al-Lahham, Natalia Levina, Mathias W Pletz, Matthias Imöhl
Streptococcus pneumoniae is a major cause of bacterial pneumonia, sepsis and meningitis worldwide. Prevalence of levofloxacin-resistant S. pneumoniae isolates in Germany and associated mutations in the quinolone resistance determining regions (QRDRs), as well as serotype distribution and multi locus sequence types (MLST) are shown. 21,764 invasive S. pneumoniae isolates from Germany, isolated in the epidemiological seasons from 2004/05 to 2014/15 were analyzed at the German National Reference Centre for Streptococci (GNRCS) for their levofloxacin resistance by micro broth dilution method...
April 19, 2017: International Journal of Medical Microbiology: IJMM
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