Synthesis and biological evaluation of novel N-(alkoxyphenyl)-aminocarbonylbenzoic acid derivatives as PTP1B inhibitors

Based on the fact that petroselinic acid showed good inhibitory activity（IC50 = 6.99μmol/L） against protein tyrosine phophatase 1B（PTP1B） in vitro,a series of novel N-（alkoxyphenyl）-aminocarbonylbenzoic acid derivatives were designed and synthesized.The results indicated that most of the derivatives showed more potent activities against PTP1B.Especially,compound 13 had obvious activity with an IC50 of 106 nmol/L in vitro.

The transient receptor potential melastatin 2:a new therapeutical target for Parkinson's disease?

The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating mechanism is dependent on reactive oxygen species. In pathological conditions, transient receptor potential melastatin 2 is overactivated, leading to a Ca~(2+) influx that alters cell homeostasis and promotes cell death. The role of transient receptor potential melastatin 2 in neurodegenerative diseases, including Alzheimer's disease and ischemia, has already been described and reviewed. However, data on transient receptor potential melastatin 2 involvement in Parkinson's disease pathology has emerged only in recent years and the issue lacks review studies that focus specifically on this topic. The present review aims to elucidate the role of the transient receptor potential melastatin 2 channel in Parkinson's disease by reviewing, summarizing, and discussing the in vitro, in vivo, and human studies published until August 2022. Here we describe fourteen studies that evaluated the transient receptor potential melastatin 2 channel in Parkinson's disease. The Parkinson's disease model used, transient receptor potential melastatin 2 antagonist and genetic approaches, and the main outcomes reported were discussed. The studies described transient receptor potential melastatin 2 activation and enhanced expression in different Parkinson's disease models. They also evidenced protective and restorative effects when using transient receptor potential melastatin 2 antagonists, knockout, or silencing. This review provides a literature overview and suggests where there is a need for more research. As a perspective point, this review shows evidence that supports transient receptor potential melastatin 2 as a pharmacological target for Parkinson's disease in the future.

NitroMAC：An instrument for the measurement of HONO and intercomparison with a long-path absorption photometer

Nitro MAC（French acronym for continuous atmospheric measurements of nitrogenous compounds） is an instrument which has been developed for the semi-continuous measurement of atmospheric nitrous acid（HONO）. This instrument relies on wet chemical sampling and detection using high performance liquid chromatography（HPLC）-visible absorption at540 nm. Sampling proceeds by dissolution of gaseous HONO in a phosphate buffer solution followed by derivatization with sulfanilamide/N-（1-naphthyl）-ethylenediamine. The performance of this instrument was found to be as follows： a detection limit of around 3 ppt with measurement uncertainty of 10% over an analysis time of 10 min. Intercomparison was made between the instrument and a long-path absorption photometer（LOPAP） during two experiments in different environments. First, air was sampled in a smog chamber with concentrations up to 18 ppb of nitrous acid. Nitro MAC and LOPAP measurements showed very good agreement. Then, in a second experiment, ambient air with HONO concentrations below250 ppt was sampled. While Nitro MAC showed its capability of measuring HONO in moderate and highly polluted environments, the intercomparison results in ambient air highlighted that corrections must be made for minor interferences when low concentrations are measured.