The diazabicyclooctanes (DBOs) are a class of serine β-lactamase (SBL) inhibitors that use a strained urea moiety as the warhead to react with the active serine residue in the active site of SBLs. The first in-class drug, avibactam, as well as several other recently approved DBOs (e.g., relebactam) or those in clinical development (e.g., nacubactam and zidebactam) potentiate activity of β-lactam antibiotics, to various extents, against carbapenem-resistant Enterobacterales (CRE) carrying class A, C, and D SBLs; however, none of these are able to rescue the activity of β-lactam antibiotics against carbapenem-resistant Acinetobacter baumannii (CRAB), a WHO “critical priority pathogen” producing class D OXA-type SBLs. Herein, we describe the chemical optimization and resulting structure–activity relationship, leading to the discovery of a novel DBO, ANT3310, which uniquely has a fluorine atom replacing the carboxamide and stands apart from the current DBOs in restoring carbapenem activity against OXA-CRAB as well as SBL-carrying CRE pathogens.

No abstract

A series of novel 1,2,3-triazole-etodolac hybrids (6a-l) were designed and synthesized as potent anticancer molecules. The synthesis strongly relied on Huisgen's 1,3-dipolar cycloaddition between etodolac azide 3 and substituted terminal alkynes 5a-l. The use of CH 2 Cl 2 as a co-solvent with H 2 O increased the reaction rate and provided the corresponding 1,2,3-triazole-etodolac hybrids (6a-l) in excellent yields compared to other organic co-solvent systems. All the compounds were screened for their in vitro anticancer activity against human A549 cell lines and compounds 6e, 6f, 6h, 6j, and 6l were found to be the best anti-cancer molecules as compared to the marketed drug doxorubicin. Kukatpally,