Discovery of Simple Diacylhydrazine-Functionalized Cinnamic Acid Derivatives as Potential Microtubule Stabilizers.

To develop novel microtubule-binding agents for cancer therapy, an array of N-cinnamoyl-N'-(substituted)acryloyl hydrazide derivatives were facilely synthesized through a two-step process. Initially, the antiproliferative activity of these title compounds was explored against A549, 98 PC-3 and HepG2 cancer cell lines. Notably, compound I23 exhibited the best antiproliferative activity against three cancer lines with IC50 values ranging from 3.36 to 5.99 µM and concurrently afforded a lower cytotoxicity towards the NRK-52E cells. Anticancer mechanism investigations suggested that the highly bioactive compound I23 could potentially promote the protofilament assembly of tubulin, thus eventually leading to the stagnation of the G2/M phase cell cycle of HepG2 cells. Moreover, compound I23 also disrupted cancer cell migration and significantly induced HepG2 cells apoptosis in a dosage-dependent manner. Additionally, the in silico analysis indicated that compound I23 exhibited an acceptable pharmacokinetic profile. Overall, these easily prepared N-cinnamoyl-N'-(substituted)acryloyl hydrazide derivatives could serve as potential microtubule-interacting agents, probably as novel microtubule-stabilizers.

Antibacterial activities against Ralstonia solanacearum and Xanthomonas oryzae pv. oryzae of 6-chloro-4-(4-substituted piperazinyl)quinazoline derivatives.

In this letter, a variety of simple 6-chloro-4-(4-substituted piperazinyl)quinazoline derivatives was prepared. Preliminary bioassays revealed that these compounds showed good antibacterial activities toward phytopathogens Ralstonia solanacearum and Xanthomonas oryzae pv. oryzae (Xoo). Among these derivatives, compounds 5a, 5d, 5e, 5f, 5p, 5q, 6b, and 6d exhibited potent inhibition effects against R. solanacearum with EC50 within 4.60-9.94 µg/mL, especially, compound 5g exerted the strongest activity with EC50 of 2.72 µg/mL; compound 6b possessed the best inhibitory activity toward Xoo with EC50 of 8.46 µg/mL. Subsequently, a good predictive three-dimensional quantitative structure-activity relationship (3D-QSAR) model was constructed via CoMFA to direct the future structural modification and optimization. Furthermore, the pathogens' topological studies were performed to explore the possible antibacterial mechanism. Given their simple frameworks and facile synthesis, title compounds can serve as the potential antibacterial leads.

Highly Selective and Sensitive Detection of Biogenic Defense Phytohormone Salicylic Acid in Living Cells and Plants Using a Novel and Viable Rhodamine-Functionalized Fluorescent Probe.

Detecting plant-derived signal molecules using fluorescent probes is a key topic and a huge challenge for scientists. Salicylic acid (SA), a vital plant-derived defense hormone, can activate global transcriptional reprogramming to systemically express a network of prominent pathogenesis-related proteins against invasive microorganisms. This strategy is called systemic acquired resistance (SAR). Therefore, monitoring the dynamic fluctuations of SA in subcellular microenvironments can advance our understanding of different physiological and pathological functions during the SA-induced SAR mechanism, thus benefiting the discovery and development of novel immune activators that contribute to crop protection. Here, detection of signaling molecule SA in plant callus tissues was first reported and conducted by a simple non-fluorescent rhodamine-tagged architecture bearing a flexible 2-amino-N,N-dimethylacetamide pattern. This study can markedly advance and promote the usage of fluorescent SA probes for distinguishing SA in the plant kingdom.