Synthesis and evaluation of small molecule inhibitors of LSD1 for use against MYCN-expressing neuroblastoma.

The epigenetic regulator lysine specific demethylase 1 (LSD1), a MYCN cofactor, cooperatively silences MYCN suppressor genes. Furthermore, LSD1 has been correlated with adverse effects in neuroblastic tumors by propagating an undifferentiated, malignant phenotype. We observed that high LSD1 mRNA expression in MYCN-expressing neuroblastoma (NB) correlated with poor prognosis, implicating LSD1 as an oncogenic accomplice in high-grade NB.

New Transmission-Selective Antimalarial Agents through Hit-to-Lead Optimization of 2-([1,1'-Biphenyl]-4-carboxamido)benzoic Acid Derivatives.

Malaria elimination requires multipronged approaches, including the application of antimalarial drugs able to block human-to-mosquito transmission of malaria parasites. The transmissible gametocytes of Plasmodium falciparum seem to be highly sensitive towards epidrugs, particularly those targeting demethylation of histone post-translational marks. Here, we report exploration of compounds from a chemical library generated during hit-to-lead optimization of inhibitors of the human histone lysine demethylase, KDM4B.

Dialing in Direct Air Capture of CO by Crystal Engineering of Bisiminoguanidines.

Direct air capture (DAC) technologies that extract carbon dioxide from the atmosphere via chemical processes have the potential to restore the atmospheric CO concentration to an optimal level. This study elucidates structure-property relationships in DAC by crystallization of bis(iminoguanidine) (BIG) carbonate salts. Their crystal structures are analyzed by X-ray and neutron diffraction to accurately measure key structural parameters including molecular conformations, hydrogen bonding, and π-stacking.

Surprisingly selective sulfate extraction by a simple monofunctional di(imino)guanidinium micelle-forming anion receptor.

We report a novel di(imino)guanidinium anion extractant with unparalleled selectivity for sulfate in a liquid-liquid separation system. In addition to a 4.4 order-of-magnitude enhancement in affinity compared to a standard benchmark, our alkylated di(imino)guanidinium receptor is economically synthesized and features good compatibility with application-relevant aliphatic solvents.