Eight of analogues of distamycin, potential minor-groove binders, were synthesized and tested for in-vitro cytotoxicity towards human breast cancer cells MCF-7 and MDA-MB-231. The method of synthesis is simple and convenient. All of the compounds 1-8 showed antiproliferative and cytotoxic effects against both cell lines in the range 3.47 to 12.53 microM for MDA-MB-231 and 4.35 to 12.66 microM for MCF-7. All compounds demonstrated activity against DNA topoisomerases I and II at a concentration of 50 microM. The ethidium bromide assay showed that these compounds bind to plasmid pBR322, yet weaker than distamycin. Further investigations concerning the mechanism of cytotoxicity are now in progress, but the IC(50) values suggest that synthetic distamycin analogues with a free amino group, 3-4 and 7-8, can serve as potential carriers of strong acting elements, e. g. alkylating groups.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ardp.200800122 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and Evaluation of Novel DNA Minor Groove Binders as Antiamoebic Agents.
Antibiotics (Basel)
July 2022
College of Arts and Sciences, American University of Sharjah, University City, Sharjah P.O. Box. 26666, United Arab Emirates.
The free-living amoeba is responsible for the central nervous infection granulomatous amoebic encephalitis and sight-threatening infection . Moreover, no effective treatment is currently present, and a combination drug therapy is used. In this study, twelve DNA minor groove binders (MGBs) were synthesized and tested for their antiamoebic activity via amoebicidal, encystation, excystation, and cytopathogenicity assays.
View Article and Find Full Text PDFSpecific stabilization of promoter G-Quadruplex DNA by 2,6-disubstituted amidoanthracene-9,10-dione based dimeric distamycin analogues and their selective cancer cell cytotoxicity.
Eur J Med Chem
June 2020
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560012, India; School of Applied & Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata, 700032, India. Electronic address:
We have designed and synthesized anthraquinone containing compounds which have oligopyrrole side chains of varying lengths. These compounds stabilized the G-quadruplex DNA formed in the promoter regions of c-MYC oncogenes selectively over the duplex DNA. These observations were recorded using UV-vis spectroscopic titrations, fluorescence measurements and circular dichroism (CD) spectral titrations.
View Article and Find Full Text PDFNovel distamycin analogues that block the cell cycle of African trypanosomes with high selectivity and potency.
Eur J Med Chem
March 2020
Group Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Montevideo, Uruguay. Electronic address:
Polyamides-based compounds related to the Streptomycetal distamycin and netropsin are potent cytostatic molecules that bind to AT-rich regions of the minor groove of the DNA, hence interfering with DNA replication and transcription. Recently, derivatives belonging to this scaffold have been reported to halt the proliferation of deadly African trypanosomes by different and unrelated mechanisms. Here we describe the synthesis and preliminary characterization of the anti-trypanosomal mode of action of new potent and selective distamycin analogues.
View Article and Find Full Text PDFCarbocyclic Analogues of Distamycin and Netropsin.
Mini Rev Med Chem
January 2019
Department of Organic Chemistry, Medical University, Bialystok 15-222, Mickiewicza Street 2c, Poland.
The DNA as the depository of genetic information is a natural target for chemotherapy. A lot of anticancer and antimicrobial agents derive their biological activity from their selective interaction with DNA in the minor groove and from their ability to interfere with biological processes such as enzyme catalysis, replication and transcription. The discovery of the details of minor groove binding drugs, such as netropsin and distamycin A, oligoamides built of 4-amino-1-methylpyrrole-2-carboxylic acid residues, allowed to develop various DNA sequence-reading molecules, named lexitropsins, capable of interacting with DNA precisely, strongly and with a high specificity, and at the same time exhibiting significant cytotoxic potential.
View Article and Find Full Text PDFThe synthesis and biological activity of a variety of analogues to the naturally occurring antibacterial and antifungal Distamycin A were explored by a number of authors. These compounds were subject to a large array of assays. Some of these compounds showed high activity against a range of Gram-positive, Gram-negative bacteria as well as fungi.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!