A Novel Mechanism of Action Natural Product for Treatment of Drug-Resistant Gonorrhea

Project Summary/Abstract: This project seeks to develop a new class of antibiotics against Neisseria gonorrhoeae (NG). NG is considered to be of the highest threat level by the CDC due to its propensity to rapidly develop drug resistance. CFD Research has discovered a novel natural product (NP) with potent NG activity, which we seek to develop here. Aim 1 will build on our established medicinal chemistry program to diversify and optimize the NP’s scaffold for improved potency, cytotoxicity and drug-like properties. Aim 2 will test the in vivo efficacy of the best analogues from Aim 1 in an established mouse model of NG infection. During Phase II, these data will drive further medicinal chemistry design and synthesis of a lead series. Mechanism of action will be elucidated. Followed by in vivo toxicity, and pharmacokinetics to produce an optimized lead compound for further preclinical development as a novel NG antibiotic.