title: Bioreductively Activated Reactive Oxygen Species (ROS) Generators as MRSA Inhibitors.
abstract: The number of cases of drug resistant Staphylococcus aureus infections is on the rise globally and new strategies to identify drug candidates with novel mechanisms of action are in urgent need. Here, we report the synthesis and evaluation of a series of benzo[b]phenanthridine-5,7,12(6H)-triones, which were designed based on redox-active natural products. We find that the in vitro inhibitory activity of 6-(prop-2-ynyl)benzo[b]phenanthridine-5,7,12(6H)-trione (1f) against methicillin-resistant Staphylococcus aureus (MRSA), including a panel of patient-derived strains, is comparable or better than vancomycin. We show that the lead compound generates reactive oxygen species (ROS) in the cell, contributing to its antibacterial activity.
authors: Indian Institute of Science Education and Research Pune , Dr. Homi Bhabha Road, Pune, 411008 Maharashtra, India.
authors: Vinayak S
authors: VS
authors: Khodade
authors: Indian Institute of Science Education and Research Pune , Dr. Homi Bhabha Road, Pune, 411008 Maharashtra, India.
authors: Mallojjala
authors: M
authors: Sharath Chandra
authors: Vitas Pharma Research Private Limited, Technology Business Incubator, University of Hyderabad , C. R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors: Ankita
authors: A
authors: Banerjee
authors: Vitas Pharma Research Private Limited, Technology Business Incubator, University of Hyderabad , C. R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors: Surobhi
authors: S
authors: Lahiri
authors: Vitas Pharma Research Private Limited, Technology Business Incubator, University of Hyderabad , C. R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors: Mallikarjuna
authors: M
authors: Pulipeta
authors: Vitas Pharma Research Private Limited, Technology Business Incubator, University of Hyderabad , C. R. Rao Road, Gachibowli, Hyderabad 500046, India.
authors: Radha
authors: R
authors: Rangarajan
authors: Indian Institute of Science Education and Research Pune , Dr. Homi Bhabha Road, Pune, 411008 Maharashtra, India.
authors: Harinath
authors: H
authors: Chakrapani
keywords: DNA damage; Drug resistance; MRSA; RecA; reactive oxygen species; superoxide radical