Human topoisomerase II (topoII) enzymes are validated anticancer drug targets due to their association with cancer cell proliferation. The clinically available topoII targeted anticancer drugs such as etoposide, often show harmful side effects and drug resistance. Therefore, new studies to design topoII inhibitors are crucial for the discovery of novel, potent and safer anti-cancer therapeutics. <br/><br/>We present the outcome of a drug design campaign to optimize compounds centered on a recently patented chemical class of topoIIα inhibitors by our group. We use alchemical binding free energy (ABFE) calculations to predict the relative binding free energy of new compounds to topoIIα with respect to the lead compound in our previous studies. ABFE calculations have proven to be fast, robust, accurate, and reliable in optimizing lead compounds in drug design. We integrate our calculations with chemical synthesis and biochemical characterizations for the rational design of new topoII inhibitors.

Design, synthesis, and biochemical characterization of novel human topoisomerase II inhibitors guided by alchemical binding free energy calculations

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.