Green Synthesis of Tetrahydropyrazino[2,1-a:5,4-a']diisoquinolines as SARS-CoV-2 Entry Inhibitors.

A class of tetrahydropyrazino[2,1-a:5,4-a']diisoquinoline derivatives were synthesized under environmentally friendly conditions using water as the solvent. The 3-D structures of some synthesized compounds were determined by X-ray diffraction. Since naturally occurring isoquinoline alkaloids have significant antiviral activities against a wide range of viruses, including coronaviruses, the synthesized compounds were assayed for their inhibitory activities against SARS-CoV-2.

Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors.

A class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC range of 0.001-0.

Pterostilbene carboxaldehyde thiosemicarbazone, a resveratrol derivative inhibits 17β-Estradiol induced cell migration and proliferation in HUVECs.

Angiogenesis plays important roles in tumor growth and metastasis, thus development of a novel angiogenesis inhibitor is essential for the improvement of therapeutics against cancer. Thrombospondins-1 (TSP-1) is a potent endogenous inhibitor of angiogenesis that acts through direct effects on endothelial cell migration, proliferation, survival, and activating apoptotic pathways. TSP-1 has been shown to disrupt estrogen-induced endothelial cell proliferation and migration.

Understanding the mode of action of a pterostilbene derivative as anti-inflammatory agent.

Inflammatory response plays an important role not only in the normal physiology, but also in the pathology of certain diseases such as cancers. In our previous study, we found a novel derivative of pterostilbene (PTER), to be an effective inducer of apoptosis in human breast and prostate cancer cells affecting various cellular targets. Herein, we further attempted to investigate its anti-inflammatory potential followed by its probable mode of action.