Janus kinase (JAK) is a non receptor tyrosine protein kinase, which has attracted wide attention and JAK inhibitors are mainly used to screen therapeutic drugs for hematological diseases, tumors, rheumatoid arthritis (RA) and psoriasis. Filgotinib is an oral small molecule JAK inhibitor which is currently at the clinical stage to treat Crohn's disease (CD) and rheumatoid arthritis. In this study, we designed novel triazolopyridine derivatives A1-A4 using Filgotinib as the lead compound, then replaced cyclopropane with trifluoromethane and replaced triazolopyridine with imidazopyrazine to get B1-B4 by isosteric principle of bioelectronics. These compounds were prepared in this work, and the corresponding effects against JAK1, JAK2 and JAK3 were assessed. The results indicated that B2 had stronger inhibitory effect on JAK1 and JAK3. A1 and A2 showed a good inhibitory effect on JAK1. Molecular docking results showed that compounds A1, A2 and B2 bind well to protein binding sites. These compounds can supply leading compounds for developing rheumatoid arthritis and Crohn's drugs.

Purpose α-pinene was a chemical compound which was extracted from pine needles oil, and it exerted effects on various diseases. However, the effect of α-pinene on cervical cancer had not been reported. The goal of this study was to explore the anti-tumor role of α-pinene.Methods Methyl thiazolyl tetrazolium (MTT) method was used to detect cytotoxicity of α-pinene. Flow cytometry was used to quantify the cell cycle and apoptosis. TUNEL staining was also performed for the revalidation of apoptosis. QRT-PCR and western blot was implemented to detect the expression levels of apoptosis genes and miR-34a-5p. Tumor-bearing nude mouse models was adopted to assess the antitumor action of α-pinene in vivo. ResultsThe results displayed α-pinene restrained proliferation of Hela cells in G1 phase and induced Hela cell apoptosis, which was related to up-regulating expressions of Bax, Bid, Caspase-9, Caspase-3, miR-34a-5p and down-regulating the expression of Bcl-2. Afterwards, α-Pinene could regulate miR-34a-5p/Bcl-2 pathway. Furthermore, α-pinene treatment also induced apoptosis in xenografts tumor models. The uorescence intensity of Bax, Bid, Caspase-9, Caspase-3 increased and uorescence intensity of Bcl-2 decreased.Conclusions Our research demonstrated α-pinene could restrain the development of cervical cancer growth, and it might be an effective chemical compound for therapy of cervical cancer.

Bicyclic phloroglucinol is a phenolic compound which mainly exist in Dryopteris fragrans (L.) Schott with antiinflammatory, antithrombotic, antifungal and antitumor activity. Although a series of anticancer agents target various tumors under clinical trials, different limitations hinder their clinical development and novel targeting chemical agents are required. Herein, we have made a number of modifications around the scaffold of the phloroglucinol. The results of antitumor activities reveal that compound A5 against A549 cells and compound A3 against HepG2 and McF‐7 cells were best with a degree of concentration dependence, which stronger than that of positive control 5‐FU, and compound A3 and A5 display lower cytotoxicity to normal cells. The molecule docking studies indicate protein Bcl‐xl and Mcl‐12 may be a potential target of these compounds. In general, A3 and A5 with potent binding affinity and good efficacy have the potential to develop into antitumor lead compounds which also deserve further study.