Lead Identification of 8-(Methylamino)-2-oxo-1,2-dihydroquinoline Derivatives as DNA Gyrase Inhibitors: Hit-to-Lead Generation Involving Thermodynamic Evaluation
Fumihito Ushiyama, Hideaki Amada, Tomoki Takeuchi, Nozomi Tanaka-Yamamoto, Harumi Kanazawa, Koichiro Nakano, Masashi Mima, Aiko Masuko, Iichiro Takata, Kosuke Hitaka, Kunihiko Iwamoto, Hiroyuki Sugiyama, Norikazu Ohtake
Abstract
value of 0.0017 μM. In this study, we demonstrated the use of ITC for primary fragment screening, followed by structural optimization to obtain lead compounds, which advanced into further optimization for creating novel antibacterial agents.
Topics & Concepts
DNA gyraseChemistryIsothermal titration calorimetryCombinatorial chemistryQuinoloneTopoisomerase IVLead compoundDNAEscherichia coliStereochemistryBiochemistryAntibioticsIn vitroGeneCancer therapeutics and mechanismsAntibiotic Resistance in BacteriaSynthesis and Biological Evaluation