Structure-activity relationship study of small-molecule inhibitor of Atg12-Atg3 protein-protein interaction.

Autophagy is a catabolic process that was described to play a critical role in advanced stages of cancer, wherein it maintains tumor cell homeostasis and growth by supplying nutrients. Autophagy is also described to support alternative cellular trafficking pathways, providing a non-canonical autophagy-dependent inflammatory cytokine secretion mechanism. Therefore, autophagy inhibitors have high potential in the treatment of cancer and acute inflammation.

High-Throughput Fluorescent Assay for Inhibitor Screening of Proteases from RNA Viruses.

Spanish flu, polio epidemics, and the ongoing COVID-19 pandemic are the most profound examples of severe widespread diseases caused by RNA viruses. The coronavirus pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demands affordable and reliable assays for testing antivirals. To test inhibitors of viral proteases, we have developed an inexpensive high-throughput assay based on fluorescent energy transfer (FRET).

Remdesivir triphosphate can efficiently inhibit the RNA-dependent RNA polymerase from various flaviviruses.

Remdesivir was shown to inhibit RNA-dependent RNA-polymerases (RdRp) from distinct viral families such as from Filoviridae (Ebola) and Coronaviridae (SARS-CoV, SARS-CoV-2, MERS). In this study, we tested the ability of remdesivir to inhibit RdRps from the Flaviviridae family. Instead of remdesivir, we used the active species that is produced in cells from remdesivir, the appropriate triphosphate, which could be directly tested in vitro using recombinant flaviviral polymerases.

Reactivity of boraguanidinato germylenes toward carbonyl compounds and isocyanides: C-O, C-F and C-N bond activation.

The reactions of two equivalents of germylene [(i-Pr)NB(N-2,6-MeCH)]Ge (1) with carbonyl compounds RC(O)R' resulted in carbonyl functionality activation and the formation of 4-(R,R')-1,2-digerma-3-oxa-cyclobutanes (R/R' = Ph/CF (2) or CF/H (3)). Surprisingly, the analogous reaction of 1 with CFC(O)Me led to the insertion of the germanium atom into the C-F bond of the perfluorophenyl group, thus producing a spiro compound (4) with a germanium atom sharing 1,2-digerma-3,5-diaza-4-bora-cyclopentane and 1-germa-2,4-diaza-3-boracyclobutane rings. Furthermore, the reaction of 1 with 2e donors was investigated.

Diverse reactivity of a boraguanidinato germylene toward organic pseudohalides.

The reactions of the boraquanidinato germylene (i-Pr)2NB(NDmp)2Ge (1) (Dmp = 2,6-Me2C6H3) with RN3 and RNCS produced rare examples of Ge2N and Ge3S rings, while the treatment of 1 with RNCO led to an insertion into the N-Ge bond leading to a novel type of germylene stabilized within a six membered ring, i.e. [N(R)C(O)N(Dmp)B(N(i-Pr)2)N(Dmp)]Ge (R = t-Bu or Ad).

Facile activation of alkynes with a boraguanidinato-stabilized germylene: a combined experimental and theoretical study.

A boraguanidinato-stabilized germylene, [(i-Pr)NB(N-2,6-MeCH)]Ge, reacts with alkynes RC[triple bond, length as m-dash]CR selectively in a 2 : 1 molar ratio to afford 3,4-R,R'-1,2-digermacyclobut-3-enes 1a-e as the products of formal [2 + 2 + 2] cyclization [R/R' = Me/Me (1a), Ph/Ph (1b), Ph/H (1c), t-Bu/H (1d) and Cy/H (1e)]. Ferrocenyl-substituted alkynes react similarly, yielding the corresponding ferrocenylated 3,4-R,R'-1,2-digermacyclobut-3-enes 2a-d [where R/R' = Fc/H (2a), Fc/Me (2b), Fc/Ph (2c), and Fc/Fc (2d); Fc = ferrocenyl]. By contrast, only one of the triple bonds available in conjugated diynes RC[triple bond, length as m-dash]CC[triple bond, length as m-dash]CR is activated with the germylene, while the second one remains intact even in the presence of an excess of the germylene.