3 years ago

Computational study of curcumin analogues by targeting DNA topoisomerase II: a structure-based drug designing approach

Rajesh Kumar Kesharwani, Dev Bukhsh Singh, Durg Vijay Singh, Krishna Misra

Abstract

Curcumin, a golden yellow pigment present in the spice turmeric, has pleiotropic chemopreventive and therapeutic active compound against many diseases including cancer. It has been reported that curcumin acts as a topoisomerase II inhibitor and it was found that even concentration of 50 µM of curcumin in vitro is active in a similar fashion as etoposide (antineoplastic agent). Topoisomerases (type I and type II) are enzymes that regulate the overwinding or underwinding of DNA by cutting the phosphate bond of one or two strands of DNA, respectively. Topoisomerase II was selected as target, since it affects both strands of DNA. The present in silico study about designing curcumin analogues as better inhibitors of topoisomerase vis-à-vis curcumin is based on ADME filtering and docking simulation using Schrödinger suite. The docking simulation result suggested that out of 1000 designed curcumin analogues using ligbuilder tool and curcumin as a lead, 293 screened analogues show good binding affinity at the active site of Human DNA topoisomerase II in comparison to known drug Salvicine. The top five analogues with best binding affinity was shown by ligand1_826, ligand1_758, ligand1_976, ligand1_956 and ligand1_827 with glide scores − 16.70, − 16.03, − 15.45, − 15.43 and − 15.09, respectively. Therefore it is possible that screened curcumin analogues can be used as lead molecules for screening of ligand database and future chemopreventive agents.

Publisher URL: https://link.springer.com/article/10.1007/s13721-018-0179-8

DOI: 10.1007/s13721-018-0179-8

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.