scholarly journals Indolo[2,3-b]quinoline derivatives as novel promising antitumor agents

2016 ◽  
Author(s):  
Lukasz Kaczmarek ◽  
Katarzyna Badowska-Rosłonek ◽  
Anna Jaromin ◽  
Wojciech Łuniewski ◽  
Wanda Peczyńska-Czoch ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Topoisomerase Ii ◽  
Antitumor Agents ◽  
Aqueous Media ◽  
Human Tumors ◽  
Quinoline Derivatives ◽  
Dna Topoisomerase ◽  
Cryptolepis Sanguinolenta

In the search for novel antineoplastic compounds we have found that four-membered, linear 5,11-dimethyl -5H- indolo[2,3-b]quinoline (DIMIQ) reveals cytostatic activity in vitro and moderate antitumor activity in vivo in mice melanoma B16 as well as leukemias L1210 and P388. Preliminary studies showed that DIMIQ stabilizes DNA-topoisomerase II complex. Some years later indolo[2,3-b]quinoline was found as an alkaloid neocryptolepine in the West African shrub Cryptolepis sanguinolenta. Unfortunately, DIMIQ’s high toxicity, lack of selectivity and very low solubility in aqueous media seriously limit the practical use of this compound as an anticancer drug. Extensive research on the structure-activity relationships of different indolo[2,3-b]quinoline derivatives showed that the position and type of the substituent is conclusive both to the antitumor activity and general toxicity of the compound. These studies led us to discover derivatives of DIMIQ which exhibit very low toxicity against normal cells and are highly toxic against selected human tumors. These derivatives are soluble in water and some of them are able to overcome multidrug resistance in human tumors cells.

scholarly journals Indolo[2,3-b]quinoline derivatives as novel promising antitumor agents

2016 ◽  
Author(s):  
Lukasz Kaczmarek ◽  
Katarzyna Badowska-Rosłonek ◽  
Anna Jaromin ◽  
Wojciech Łuniewski ◽  
Wanda Peczyńska-Czoch ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Topoisomerase Ii ◽  
Antitumor Agents ◽  
Aqueous Media ◽  
Human Tumors ◽  
Quinoline Derivatives ◽  
Dna Topoisomerase ◽  
Cryptolepis Sanguinolenta

In the search for novel antineoplastic compounds we have found that four-membered, linear 5,11-dimethyl -5H- indolo[2,3-b]quinoline (DIMIQ) reveals cytostatic activity in vitro and moderate antitumor activity in vivo in mice melanoma B16 as well as leukemias L1210 and P388. Preliminary studies showed that DIMIQ stabilizes DNA-topoisomerase II complex. Some years later indolo[2,3-b]quinoline was found as an alkaloid neocryptolepine in the West African shrub Cryptolepis sanguinolenta. Unfortunately, DIMIQ’s high toxicity, lack of selectivity and very low solubility in aqueous media seriously limit the practical use of this compound as an anticancer drug. Extensive research on the structure-activity relationships of different indolo[2,3-b]quinoline derivatives showed that the position and type of the substituent is conclusive both to the antitumor activity and general toxicity of the compound. These studies led us to discover derivatives of DIMIQ which exhibit very low toxicity against normal cells and are highly toxic against selected human tumors. These derivatives are soluble in water and some of them are able to overcome multidrug resistance in human tumors cells.

scholarly journals Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives as antitumor agents: in vitro and in vivo antitumor activity, cell cycle arrest and apoptotic response

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24376-24385 ◽  
Author(s):  
Wen-Bin Kuang ◽  
Ri-Zhen Huang ◽  
Yi-Lin Fang ◽  
Gui-Bin Liang ◽  
Chen-Hui Yang ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antitumor Agents ◽  
Quinoline Derivatives ◽  
Apoptotic Response ◽  
Design Synthesis ◽  
Cycle Arrest ◽  
In Vivo Antitumor Activity ◽  
Combination Principle

A series of novel 2-chloro-3-(1H-benzo[d]imidazol-2-yl)quinoline derivatives were designed and synthesized as antitumor agents under the combination principle. The antitumor activity and mechanisms were then evaluated.

The in vivo distribution and dynamics of DNA topoisomerase II in Drosophila embryonic nuclei and chromosomes

1993 ◽  
Vol 51 ◽  
pp. 74-75
Author(s):  
Jason R. Swedlow ◽  
Neil Osheroff ◽  
Tim Karr ◽  
John W. Sedat ◽  
David A. Agard
Keyword(s):  
Topoisomerase Ii ◽  
Biochemical Characterization ◽  
Developmental Cycle ◽  
Dna Topoisomerase Ii ◽  
Chromosomal Distribution ◽  
Dna Topoisomerase ◽  
Ideal System ◽  
Dnase Treatment

DNA topoisomerase II is an ATP-dependent double-stranded DNA strand-passing enzyme that is necessary for full condensation of chromosomes and for complete segregation of sister chromatids at mitosis in vivo and in vitro. Biochemical characterization of chromosomes or nuclei after extraction with high-salt or detergents and DNAse treatment showed that topoisomerase II was a major component of this remnant, termed the chromosome scaffold. The scaffold has been hypothesized to be the structural backbone of the chromosome, so the localization of topoisomerase II to die scaffold suggested that the enzyme might play a structural role in the chromosome. However, topoisomerase II has not been studied in nuclei or chromosomes in vivo. We have monitored the chromosomal distribution of topoisomerase II in vivo during mitosis in the Drosophila embryo. This embryo forms a multi-nucleated syncytial blastoderm early in its developmental cycle. During this time, the embryonic nuclei synchronously progress through 13 mitotic cycles, so this is an ideal system to follow nuclear and chromosomal dynamics.

scholarly journals Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

The C-terminal domain of Saccharomyces cerevisiae DNA topoisomerase II

1994 ◽  
Vol 14 (5) ◽  
pp. 3197-3207
Author(s):  
P R Caron ◽  
P Watt ◽  
J C Wang
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Nuclear Localization ◽  
Topoisomerase Ii ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Mutant Proteins ◽  
Terminal Domain ◽  
Catalytically Active

A set of carboxy-terminal deletion mutants of Saccharomyces cerevisiae DNA topoisomerase II were constructed for studying the functions of the carboxyl domain in vitro and in vivo. The wild-type yeast enzyme is a homodimer with 1,429 amino acid residues in each of the two polypeptides; truncation of the C terminus to Ile-1220 has little effect on the function of the enzyme in vitro or in vivo, whereas truncations extending beyond Gln-1138 yield completely inactive proteins. Several mutant enzymes with C termini in between these two residues were found to be catalytically active but unable to complement a top2-4 temperature-sensitive mutation. Immunomicroscopy results suggest that the removal of a nuclear localization signal in the C-terminal domain is likely to contribute to the physiological dysfunction of these proteins; the ability of these mutant proteins to relax supercoiled DNA in vivo shows, however, that at least some of the mutant proteins are present in the nuclei in a catalytically active form. In contrast to the ability of the catalytically active mutant proteins to relax supercoiled intracellular DNA, all mutants that do not complement the temperature-dependent lethality and high frequency of chromosomal nondisjunction of top2-4 were found to lack decatenation activity in vivo. The plausible roles of the DNA topoisomerase II C-terminal domain, in addition to providing a signal for nuclear localization, are discussed in the light of these results.

scholarly journals Effect of etoposide on grass pea DNA topoisomerase II: an in silico, in vivo, and in vitro assessments

2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Aveek Samanta ◽  
Tilak Raj Maity ◽  
Sudip Das ◽  
Animesh Kumar Datta ◽  
Siraj Datta
Keyword(s):  
In Silico ◽  
Topoisomerase Ii ◽  
Cost Effective ◽  
Colchicine Treatment ◽  
Grass Pea ◽  
Dna Topoisomerase ◽  
Ammonium Sulphate Precipitation ◽  
In Silico Study

Abstract Background Etoposide is one of the most potential anti-cancerous drugs that targets topoisomerase II (topoII) and inhibits its activity by ligation with the DNA molecule. Results In silico study confirmed that the etoposide-binding sites of topoII are conserved among the plants and human. The efficacy of the drug on plant system was initially assessed using germinated grass pea (Lathyrus sativus L.) seedlings (in vivo) in relation to radicle length and mitotic index. The callus system (in vitro) was also used to elucidate the effect of etoposide on callus growth kinetics. Furthermore, it was observed that etoposide able to inhibit the division of polyploid cells induced by colchicine treatment (0.5%, 8 h). To determine the molecular interaction, topoII was isolated from young grass pea leaves using polyethylene glycol fractionation and ammonium sulphate precipitation followed by column chromatography on CM-Sephadex (C-25). The plasmid linearization assays by isolated plant topoII in the presence of etoposide significantly revealed the functional similarity of plants and human topoII. Results indicated that the effect of etoposide on plant topoII is significant. Conclusions This study may pave the way to develop a plant-based assay system for screening the topoisomerase targeted anti-cancerous drugs, as it is convenient and cost-effective.

scholarly journals Screening of Antibacterial, Thrombolytic, Membrane Stabilizing, Anti-inflammatory and Antitumor Activity of Citrus assamensis Leaf Extracts

2018 ◽  
Vol 10 (2) ◽  
pp. 195-210
Author(s):  
M. Shahriar ◽  
M. A. Bhuiyan ◽  
M. S. Rana
Keyword(s):  
Antitumor Activity ◽  
Antitumor Agents ◽  
Chloroform Extract ◽  
Haemolytic Activity ◽  
Hypotonic Solution ◽  
Leaf Extracts ◽  
Thrombolytic Activity ◽  
Anti Inflammatory

The methanol, ethanol and chlorofom leaf extracts of Satkara, Citrus assamensis (family: Rutaceae), were subjected to in vitro anti-bacterial, thrombolytic, membrane stabilizing and in vivo anti-inflammatory and antitumor activity tests. The chloroform extract of C. assamensis showed the most important spectrum of activity against Bacillus subtilis, Bacillus cereus, Sarcina lutea among 6 gram positive and against 11 gram negative bacteria at the concentration of 1000 μg/disc, while the range of zones of inhibition were within 7-16 mm. Among the tested three extracts CHCl3 extract showed potent thrombolytic activity and hypotonic solution induced haemolytic activity where the percentages of inhibition were found to be 35% and 55% respectively. All the extracts established significant (p<0.05) anti-inflammatory effect by regulating biphasic inflammatory process induced by carrageenan. The leaf extract dose-dependently and significantly decreases the number of EAC cell count and inhibition of cell growth in comparison to the EAC control and standard. The results obtained in the present study indicate that, C. assamensis leaf can be a potential source of anti-bacterial, thrombolytic, membrane stabilizing, anti-inflammatory and antitumor agents.

DNA topoisomerase II cleavage of telomeres in vitro and in vivo

1998 ◽  
Vol 1395 (1) ◽  
pp. 110-120 ◽  
Author(s):  
Hee Jei Yoon ◽  
In Young Choi ◽  
Mi Ran Kang ◽  
Soung Soo Kim ◽  
Mark T Muller ◽  
...  
Keyword(s):  
Topoisomerase Ii ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase
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