Research Article
Reversal of P-glycoprotein Mediated Multidrug Resistance in MCF-7/R Cancer Cells by Esculetin Derivatives: Experimental and MD Simulation Studies
Issue:
Volume 12, Issue 3, June 2024
Pages:
30-48
Received:
1 July 2024
Accepted:
29 July 2024
Published:
27 August 2024
Abstract: Coumarins of natural origin have been explored as potential inhibitors of P-glycoprotein (P-gp). Esculetin which belongs to the class of coumarin has been derivatized with known hydrazine pharmacophores viz; benzoyl hydrazine (BH), isonicotinyl hydrazine (INH), and hydrazino benzoic acid. The homology modeling approach was used to predict the three-dimensional structure of human P-gp. An in-silico study has been performed for the structural insight into the molecular mechanism of P-gp inhibition of the esculetin derivatives by molecular docking (MD) and simulation studies. The cell cytotoxic activities of the synthesized compounds were evaluated using in-vitro studies. The sublines resistant doxorubicin (MCF-7/R) were generated and the activities of P-gp proteins were estimated using fluorescent dye accumulation assays. The E-BH showed promising P-gp inhibitory activity and cell cytotoxicity against MCF7 and MCF7/R (resistant) breast cancer cell lines. In line with experimental observations, the E-BH (Esculetin benzoyl hydrazine) has yielded the lowest energy stable complex with P-gp and is stabilized by intermolecular hydrogen bonding and more hydrophobic interactions during 100 ns of simulation. This suggested that the activity of P-gp is probably controlled by hydrophobic interactions. Performed experimental and computational studies has helped to elucidate the mechanism of P-gp inhibition by E-BH. Thus, amongst the three derivatives; E-BH exhibits greater efficacy in blocking the efflux mechanism.
Abstract: Coumarins of natural origin have been explored as potential inhibitors of P-glycoprotein (P-gp). Esculetin which belongs to the class of coumarin has been derivatized with known hydrazine pharmacophores viz; benzoyl hydrazine (BH), isonicotinyl hydrazine (INH), and hydrazino benzoic acid. The homology modeling approach was used to predict the three...
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Review Article
The Role of Exosomal Long Non-Coding RNAs in Tumors and Tumour Metabolism
Issue:
Volume 12, Issue 3, June 2024
Pages:
49-56
Received:
10 July 2024
Accepted:
12 August 2024
Published:
27 August 2024
Abstract: Long non-coding RNAs (lncRNAs) are RNAs that do not have protein-coding functions and are involved in a wide range of important regulatory processes through four modes of (1) signaling (2) guidance (3) structural backbone (4) decoying, which regulate gene expression at epigenetic, transcriptional and post-transcriptional levels. Exosomes are extracellular vesicles released by various cells, whose contents are protected from degradation and stabilized in the extracellular environment due to their lipid bilayer membrane structure, and which are thought to play an important role in many diseases, including tumors. The exosomes secreted by tumor cells and stromal cells contain proteins, nucleic acids, lipids, cytokines, transcription factors and other biologically active substances. With the help of exosomes, they are stably transported between cells and mediate the exchange of substances and information between cells in order to achieve intercellular communication, thus affecting the biological activities of target cells. Among them, lncRNAs are selectively sorted into exosomes, which can regulate tumor metabolism as well as tumor progression through exosomes in various ways. In this paper, the role of exosomal lncRNAs in the tumor microenvironment and tumor metabolism is reviewed, with a view to providing markers, targets and directions for clinical diagnosis, tumor therapy and tumor-related research.
Abstract: Long non-coding RNAs (lncRNAs) are RNAs that do not have protein-coding functions and are involved in a wide range of important regulatory processes through four modes of (1) signaling (2) guidance (3) structural backbone (4) decoying, which regulate gene expression at epigenetic, transcriptional and post-transcriptional levels. Exosomes are extrac...
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,
Neelofar Khan,
Rohit Bavi
