Related Experiment Video
Updated: May 30, 2026
Assay Development for High-Throughput Drug Screening Against Mycobacteria
Published on: October 25, 2024
High throughput discovery of heteroaromatic-modifying enzymes allows enhancement of novobiocin selectivity
Sital M Patel1, Maria de la Fuente, Song Ke
1Department of Pharmaceutical & Biological Chemistry, The School of Pharmacy, University of London, 29/39 Brunswick Square, London, WC1N 1AX, UK.
Abstract:
Glycosylated analogues of novobiocin, discovered using a broad library of enzymes, have 100-fold improved activity against breast, brain, pancreatic, lung and ovarian cancers and ablated associated off-target activity leading to an up to 2.7 × 10(4) fold increase in selectivity.
Insights
Novel glycosylated novobiocin analogues show significantly enhanced anti-cancer activity. These compounds exhibit improved selectivity, reducing off-target effects for breast, brain, pancreatic, lung, and ovarian cancers.
Area of Science:
- Medicinal Chemistry
- Oncology
- Enzymology
Background:
- Novobiocin is an antibiotic with limited clinical application due to toxicity.
- Cancer drug development requires novel compounds with improved efficacy and selectivity.
- Enzyme-catalyzed modifications offer a route to novel drug analogues.
Purpose of the Study:
- To synthesize and evaluate glycosylated analogues of novobiocin.
- To assess the anti-cancer activity and selectivity of these novel compounds.
- To investigate the potential of enzyme-discovered analogues for cancer therapy.
Main Methods:
- Utilized a broad enzyme library for the discovery of novobiocin analogues.
- Synthesized glycosylated derivatives of novobiocin.
- Tested compound activity against breast, brain, pancreatic, lung, and ovarian cancer cell lines.
- Quantified off-target activity and calculated selectivity indexes.
Main Results:
- Glycosylated novobiocin analogues demonstrated up to 100-fold increased activity against multiple cancer types.
- Associated off-target activities were significantly ablated.
- Selectivity increased by up to 2.7 × 10(4) fold compared to parent compound.
- Discovery enabled by a diverse enzyme library.
Conclusions:
- Enzyme-discovered glycosylated novobiocin analogues represent a promising new class of anti-cancer agents.
- These analogues offer superior efficacy and selectivity, potentially reducing side effects.
- Further investigation is warranted for their clinical development in oncology.
