European Journal of Medicinal Chemistry
European Journal of Medicinal Chemistry
5 years ago

A pentanoic acid derivative targeting matrix metalloproteinase-2 (MMP-2) induces apoptosis in a chronic myeloid leukemia cell line

A pentanoic acid derivative targeting matrix metalloproteinase-2 (MMP-2) induces apoptosis in a chronic myeloid leukemia cell line
Depending on our previous observations, some compounds of pentanoic acid were designed and synthesized. Characterization of the synthesized compounds was done by mass, NMR and IR spectroscopy as well as elemental analysis. Among the synthesized molecules, (2S)-5-oxo-2-[(nitrobenzene-4-yl sulfonyl) amino]-5-(pentylamino) pentanoic acid (Cpd 11) was found as a lead and potent inhibitor of matrix metalloproteinase-2 (MMP-2). Molecular modeling and enzyme inhibition studies were done to confirm the interaction or inhibitory potential of this compound. Thereafter, the biological screening was done through cytotoxicity, anti-invasion and apoptosis-related assays. Docking analysis revealed that Cpd 11 interacted with the target molecule MMP-2 and with MMP-9. However, enzyme inhibition assay showed 3-fold MMP-2 inhibition compared to MMP-9. Cytotoxicity assay showed the inhibitory potential of Cpd 11 against K562 cell line having IC50 value of 17.9 ± 0.01 μM after 48 h of incubation. The cell death was apoptotic in nature as revealed from the annexin V and sub-G1 cell cycle arrest assay. Besides this, Cpd 11 also exhibited dose dependent anti-invasive activity into K562 cell line. On the other hand, flow cytometry and western blot data revealed Cpd 11 induced downregulation of MMP-2 in K562 cell line after 48 h of incubation that might be linked with the anti-invasive and apoptotic activity furthermore. Therefore, the overall results validated each method and make this molecule as a potent MMP-2 inhibitor that blocked the invasion and could bring apoptosis at later stages in K562 cells sparing the normal ones.

Publisher URL: www.sciencedirect.com/science

DOI: S0223523417307675

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.