scholarly journals 1H-Benzimidazole derivatives as mammalian DNA topoisomerase I inhibitors.

2007 ◽  
Vol 54 (3) ◽  
pp. 561-565 ◽  
Author(s):  
A Selcen Alpan ◽  
H Semih Gunes ◽  
Zeki Topcu
Keyword(s):  
Topoisomerase I ◽  
Biological Properties ◽  
Benzimidazole Derivatives ◽  
Type I ◽  
Mass Spectral Data ◽  
Dna Topoisomerase ◽  
Mass Spectral ◽  
Elemental Analyses ◽  
Supercoil Relaxation

Benzimidazole is one of the most important heterocyclic groups manifesting various biological properties, such as antibacterial, antifungal, antimicrobial, antiprotozoal and antihelmintic activities. Several benzimidazole derivatives are also active as inhibitors of type I DNA topoisomerases. In this study, three 1H-benzimidazole derivatives with different electronic characteristics at position 5-, namely 5-chloro-4-(1H-benzimidazole-2-yl)phenol (Cpd I), 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) and 4-(1H-benzimidazole-2-yl)phenol (Cpd III), were synthesized and evaluated for their effects on mammalian type I DNA topoisomerase activity using quantitative in vitro plasmid supercoil relaxation assays. For the structure elucidation of the compounds, melting points, UV, IR, 1H NMR, 13C NMR, mass spectral data and elemental analyses were interpreted. Among the compounds, 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) manifested relatively potent topoisomerase I inhibition.

scholarly journals Flavonoids in Helichrysum pamphylicum Inhibit Mammalian Type I DNA Topoisomerase

2008 ◽  
Vol 63 (1-2) ◽  
pp. 69-74 ◽  
Author(s):  
Zeki Topcu ◽  
Bintug Ozturk ◽  
Ozlem Kucukoglu ◽  
Emrah Kilinc
Keyword(s):  
Antioxidant Capacity ◽  
Topoisomerase I ◽  
Type I ◽  
Dna Topoisomerase I ◽  
Dependent Manner ◽  
Dna Topoisomerase ◽  
Total Antioxidant ◽  
Supercoil Relaxation ◽  
Dose Dependent

DNA topoisomerases are important targets for cancer chemotherapy. We investigated the effects of a methanolic extract of Helichrysum pamphylicum on mammalian DNA topoisomerase I via in vitro plasmid supercoil relaxation assays. The extracts manifested a considerable inhibition of the enzyme’s activity in a dose-dependent manner. We also performed a HPLC analysis to identify the flavonoid content of the H. pamphylicum extract and tested the identified flavonoids; luteolin, luteolin-4-glucoside, naringenin, helichrysinA and isoquercitrin, on DNA topoisomerase I activity. The measurement of the total antioxidant capacity of the flavonoid standards suggested that the topoisomerase inhibition might be correlated with the antioxidant capacity of the plant.

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF SOME NEWER BENZIMIDAZOLE DERIVATIVES BY MANNICH REACTION

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (07) ◽  
pp. 16-22
Author(s):  
N. Kumar ◽  
D Pathak ◽  
Keyword(s):  
Salicylic Acid ◽  
Elemental Analysis ◽  
Mannich Reaction ◽  
Anthelmintic Activity ◽  
Biological Evaluation ◽  
Benzimidazole Derivatives ◽  
Good Activity ◽  
Mass Spectral Data ◽  
Mass Spectral

O-phenylenediamine and salicylic acid were used for the synthesis of 2-(1-(substituted phenylamino) methyl-1H benzo[d] imidazol-2-yl) phenol (2a-2h) derivatives by using various substituted aniline. In the first step, reaction of o-phenylenediamine and salicylic acid yielded 2-(1H-benzo[d]imidazol-2-yl) phenol (1), which on Mannich reaction with substituted aniline gave compounds (2a-2h). The structures of these compounds were characterized by IR, 1H NMR, mass spectral data and elemental analysis. Each analogue was tested in vitro for various types of pharmacological activity of this class of drugs including antibacterial, antifungal and anthelmintic activity. Among the synthesized compounds 2a act as vermifuge and no compound was found to be a vermicide. The compound 2c was found to be most active against E.coli and P. aeurigenosa and 2e be most active against B.subtilis and S.aureus. The derivative 2h shows good activity against C.albicans and A.niger.

Increased DNA topoisomerase I activity in aging human cell chromatin

1984 ◽  
Vol 4 (10) ◽  
pp. 861-868 ◽  
Author(s):  
Claude Hamelin ◽  
Lise Cousineau ◽  
Michel Dion ◽  
Jocelyn Yelle
Keyword(s):  
Topoisomerase I ◽  
Dna Unwinding ◽  
Type I ◽  
Dna Topoisomerase I ◽  
Dna Topoisomerase ◽  
Human Diploid Fibroblasts ◽  
In Vitro Aging ◽  
Age Related ◽  
Cell Age

Chromatin-associated DNA topoisomerase I activity was measured in human diploid fibroblasts during in vitro aging. No diilerence was detected as a function of cell age in the nicking and the closing activities of the DNA-unwinding enzyme. The capacity of type-I topoisomerase to relax superhelical DNA molecules was, however, increased in aged cells. An age-related increase in nucleoprotein content was also observed.

scholarly journals Design, Synthesis, and In Vitro Antimicrobial Evaluation of Fused Pyrano[3,2-e]tetrazolo[1,5-c]pyrimidines and Diazepines

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sankari Kanakaraju ◽  
P. Sagar Vijay Kumar ◽  
Bethanamudi Prasanna ◽  
G. V. P. Chandramouli
Keyword(s):  
Carbon Disulfide ◽  
Phenacyl Bromide ◽  
Mass Spectral Data ◽  
Design Synthesis ◽  
Mass Spectral ◽  
H Nmr ◽  
Elemental Analyses ◽  
Antimicrobial Evaluation ◽  
C Nmr

A series of novel pyranochromene-containing tetrazoles fused with pyrimidinethiones, pyrimidines, and diazepines 3a–f, 4a–f, and 5a–f were synthesized by condensation of the corresponding tetrazoles 2a–f with carbon disulfide, benzaldehyde, and 4-methoxy phenacyl bromide, respectively. The compound 2a–f was obtained by reaction of pyrano[3,2-c]chromenes 1a–f with sodium azide. The structures of the newly synthesized compounds 2a–f to 5a–f were established on the basis of their elemental analyses, IR, 1H NMR, 13C NMR, and mass spectral data. All of the title compounds were subjected to in vitro antibacterial testing against four pathogenic strains and antifungal screening against two fungi. Preliminary results indicate that some of them exhibited promising activities and that they deserve more consideration as potential antimicrobials.

scholarly journals Genome-wide proximity between RNA polymerase and DNA topoisomerase I supports transcription in Streptococcus pneumoniae

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009542
Author(s):  
María-José Ferrándiz ◽  
Pablo Hernández ◽  
Adela G. de la Campa
Keyword(s):  
Streptococcus Pneumoniae ◽  
Rna Polymerase ◽  
Topoisomerase I ◽  
Type I ◽  
Dna Topoisomerase I ◽  
Sequence Motifs ◽  
Dna Topoisomerase ◽  
Genome Wide

Streptococcus pneumoniae is a major cause of disease and death that develops resistance to multiple antibiotics. DNA topoisomerase I (TopoI) is a novel pneumococcal drug target. TopoI is the sole type-I pneumococcal topoisomerase that regulates supercoiling homeostasis in this bacterium. In this study, a direct in vitro interaction between TopoI and RNA polymerase (RNAP) was detected by surface plasmon resonance. To understand the interplay between transcription and supercoiling regulation in vivo, genome-wide association of RNAP and TopoI was studied by ChIP-Seq. RNAP and TopoI were enriched at the promoters of 435 and 356 genes, respectively. Higher levels of expression were consistently measured in those genes whose promoters recruit both RNAP and TopoI, in contrast with those enriched in only one of them. Both enzymes occupied a narrow region close to the ATG codon. In addition, RNAP displayed a regular distribution throughout the coding regions. Likewise, the summits of peaks called with MACS tool, mapped around the ATG codon in both cases. However, RNAP showed a broader distribution towards ATG-downstream positions. Remarkably, inhibition of RNAP with rifampicin prevented the localization of TopoI at promoters and, vice versa, inhibition of TopoI with seconeolitsine prevented the binding of RNAP to promoters. This indicates a functional interplay between RNAP and TopoI. To determine the molecular factors responsible for RNAP and TopoI co-recruitment, we looked for DNA sequence motifs. We identified a motif corresponding to a -10-extended promoter for TopoI and for RNAP. Furthermore, RNAP was preferentially recruited to genes co-directionally oriented with replication, while TopoI was more abundant in head-on genes. TopoI was located in the intergenic regions of divergent genes pairs, near the promoter of the head-on gene of the pair. These results suggest a role for TopoI in the formation/stability of the RNAP-DNA complex at the promoter and during transcript elongation.

scholarly journals Green Synthetic Protocol for (E)-1-Aryl-3-(2-morpholinoquinolin- 3-yl)prop-2-en-1-ones and Their Antimicrobial Activity

2019 ◽  
Vol 31 (9) ◽  
pp. 1895-1898
Author(s):  
Relangi Siva Subrahmanyam ◽  
Venkateswara Rao Anna
Keyword(s):  
Antimicrobial Activity ◽  
Spectral Data ◽  
1H Nmr ◽  
13C Nmr ◽  
Mass Spectral Data ◽  
In Vitro Antimicrobial Activity ◽  
Mass Spectral ◽  
Fungal Organisms

We report here an easy, efficient and green synthetic protocol for the (E)-1-aryl-3-(2-morpholinoquinolin-3-yl)prop-2-en-1-ones by the Claisen-Schmidt condensation of 2-morpholinoquinoline-3-carbaldehyde and different substituted acetophenones by using 1-butyl-3-methylimidazolium tetrafluoroborate (Bmim)BF4. The compounds were characterized by using 1H NMR, 13C NMR and mass spectral data and screened there in vitro antimicrobial activity against different bacterial and fungal organisms.

scholarly journals Internalization of Foldamer-Based DNA Mimics through a Site-Specific Antibody Conjugate to Target HER2-Positive Cancer Cells

2021 ◽  
Vol 14 (7) ◽  
pp. 624
Author(s):  
Valentina Corvaglia ◽  
Imène Ait Mohamed Amar ◽  
Véronique Garambois ◽  
Stéphanie Letast ◽  
Aurélie Garcin ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Topoisomerase I ◽  
Ovarian Cancer Cells ◽  
Cellular Functions ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Dna Topoisomerase ◽  
Antibody Conjugate ◽  
A Site

Inhibition of protein–DNA interactions represents an attractive strategy to modulate essential cellular functions. We reported the synthesis of unique oligoamide-based foldamers that adopt single helical conformations and mimic the negatively charged phosphate moieties of B-DNA. These mimics alter the activity of DNA interacting enzymes used as targets for cancer treatment, such as DNA topoisomerase I, and they are cytotoxic only in the presence of a transfection agent. The aim of our study was to improve internalization and selective delivery of these highly charged molecules to cancer cells. For this purpose, we synthesized an antibody-drug conjugate (ADC) using a DNA mimic as a payload to specifically target cancer cells overexpressing HER2. We report the bioconjugation of a 16-mer DNA mimic with trastuzumab and its functional validation in breast and ovarian cancer cells expressing various levels of HER2. Binding of the ADC to HER2 increased with the expression of the receptor. The ADC was internalized into cells and was more efficient than trastuzumab at inhibiting their growth in vitro. These results provide proof of concept that it is possible to site-specifically graft high molecular weight payloads such as DNA mimics onto monoclonal antibodies to improve their selective internalization and delivery in cancer cells.

scholarly journals Antimicrobial, Antifertility and Antiinflammatory Approach to Tetradentate Macrocyclic Complexes of Iron(II) and Manganese(II)

2002 ◽  
Vol 8 (6) ◽  
pp. 347-353 ◽  
Author(s):  
Ashu Chaudhary ◽  
D. P. Jaroli ◽  
R. V. Singh
Keyword(s):  
Molecular Weight ◽  
Reproductive Organs ◽  
Spectral Studies ◽  
Central Metal Atom ◽  
Central Metal ◽  
Testicular Sperm ◽  
Mass Spectral ◽  
Sperm Density ◽  
Elemental Analyses

Some antifertility inhibitors of 18 to 24-membered tetraazamacrocyclic complexes of iron(II) and manganese(II) have been synthesised by the template condensation using 1,3-phenylenediamine with malonic acid, succinic acid, glutaric acid and adipic acid. The reaction proceed smoothly to completion. The complexes were characterized by elemental analyses, molecular weight determinations, infrared, electronic, magnetic moment, mössbaur and mass spectral studies. The elemental analyses are consistent with the formation of the complexes [M(N4Ln)Cl2] (M = Fe(lI) or Mn(II)). All these complexes are stable and monomeric in nature as indicated by the molecular weight determinations. The spectral studies confirm the octahedral geometry around the central metal atom. The complexes have been screened in vitro against a number of fungi and bacteria to assess their growth inhibiting potential. The testicular sperm density and testicular sperm morphology, sperm motility, density of cauda epididymal spermatozoa and fertility in mating trials and biochemical parameters of reproductive organs have been examined and discussed.

Minor groove dimeric bisbenzimidazoles inhibit in vitro DNA binding to eukaryotic DNA topoisomerase I

2010 ◽  
Vol 75 (6) ◽  
pp. 695-701 ◽  
Author(s):  
O. Yu. Susova ◽  
A. A. Ivanov ◽  
S. S. Morales Ruiz ◽  
E. A. Lesovaya ◽  
A. V. Gromyko ◽  
...  
Keyword(s):  
Dna Binding ◽  
Topoisomerase I ◽  
Minor Groove ◽  
Dna Topoisomerase I ◽  
Dna Topoisomerase ◽  
Dimeric Bisbenzimidazoles ◽  
Eukaryotic Dna
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