Inhibition of the nonmevalonate pathway (NMP) of isoprene biosynthesis has been examined as a source of new antibiotics with novel mechanisms of action. Dxr is the best studied of the NMP enzymes and several reports have described potent Dxr inhibitors. Many of these compounds are structurally related to natural products fosmidomycin and FR900098, each bearing retrohydroxamate and phosphonate groups. We synthesized a series of compounds with two to five methylene units separating these groups to examine what linker length was optimal and tested for inhibition against Mtb Dxr. We synthesized ethyl and pivaloyl esters of these compounds to increase lipophilicity and improve inhibition of Mtb growth. Our results show that propyl or propenyl linker chains are optimal. Propenyl analog 22 has an IC50 of 1.07 μM against Mtb Dxr. The pivaloyl ester of 22, compound 26, has an MIC of 9.4 μg/mL, representing a significant improvement in antitubercular potency in this class of compounds.

This article examines the emotive narratives surrounding the “new normal” of social distancing practices during the first six months of the COVID-19 pandemic, as revealed by religion-focused Internet memes. In March 2020, many people were introduced to the concept of “social distancing” for the first time via news reports and media coverage of the spreading COVID-19 pandemic which led to the first lockdown. As the year progressed, social distancing discourse was combined with discussion of the practices of masking and quarantining, all of which became part of many countries’ normal routines as a public health management strategy. Over time, social distancing has become a widely used public health strategy impacting many social groups, including religious adherents and their places of worship. Memes became a discursive space where practices of social distancing and religious attitudes towards these practices were expressed and debated. By examining memes centered on American Christianity, this study reveals that memetic narratives in the early months of the pandemic indicate a positive framing of behaviors intended to help reduce the spread of COVID-19, and a negative framing of the attitudes of religious individuals and organizations who seem to privilege the cultural practices of their belief over the core values of the Christian faith.

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