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Background: Spirocyclic indoline compounds widely exist in numerous natural products and synthetic molecules with significant biological activities. In recent years, these kinds of compounds have attracted extensive attention as potent anti-tumor agents in the fields of pharmacology and chemistry. Objective: In this study, we focused on designing and synthesizing novel 1'-methylspiro[indoline- 3,4'-piperidine] derivatives, which were evaluated by preliminary bioactivity experiment in vitro and molecular docking. Materials and Methods: The key intermediate 1'-methylspiro[indoline-3,4'-piperidine] (B4) reacted with benzenesulfonyl chloride with different substituents under alkaline condition to obtain its derivatives (B5-B10). We evaluated their antiproliferative activities against A549, BEL-7402 and HeLa cell lines by MTT assay. We performed the CDOCKER module in Accelrys Discovery Studio 2.5.5 for molecular docking of compound B5, and investigated the binding modes of compound B5 with three different target proteins. Results: The results indicated that compounds B4-B10 exhibited good antiproliferative activities against the above three types of cell lines, in which compound B5 with chloride atom as electronwithdrawing substituent on a phenyl ring showed the highest potency against BEL-7402 cell lines (IC50=30.03±0.43 μg/mL). The results of molecular docking showed that the binding energies of the prominent bioactive compound B5 with CDK, c-Met, and EGFR protein crystals are -44.3583 kcal/mol, -38.3292 kcal/mol, -33.3653 kcal/mol, respectively. Conclusion: 1'-methylspiro[indoline-3,4'-piperidine] and its six derivatives were synthesized and evaluated against BEL-7402, A 549, and Hela cell lines. Compound B5 showed significant inhibition on BEL-7402 cell lines. Molecular docking assays revealed that B5 as a ligand showed strong affinity and appropriate binding pose on the amino acid residues in active sites of the tested targets, which encourage us to conduct further evaluation such as the kinase experiment.

Pine needle oil from crude extract of pine needles has been used as an anti-cancer agent in Traditional Chinese Medicine. The α-pinene is a natural compound isolated from pine needle oil which has been shown anti-cancer activity. In previous study, we found that pine needle oil exhibited significant inhibitory effect on hepatoma carcinoma BEL-7402 cells. In this study, we investigate the inhibition of α-pinene on hepatoma carcinoma BEL-7402 cells in vitro and in vivoand further explore the mechanism. The results show that liver cancer cell growth was inhibited obviously with inhibitory rate of 79.3% in vitroand 69.1% in vivo, Chk1 and Chk2 levels were upregulated, CyclinB, CDC25 and CDK1 levels were downregulated.

In this paper, a specific design strategy targeting c‐met kinase was reported based on docking modeling and topomer comparative molecular field analysis (Topomer CoMFA). A novel U‐shape conformation which is distinct from the literature was demonstrated by molecular docking among 68 U‐shape c‐met inhibitors. According to the docking results, two Topomer CoMFA models with high predictive ability were established based on the two fragment rule. The results from both docking and topomer CoMFA showed that the π–π stacking interaction with Tyr1230 and the hydrogen bond with hinge region play an important role in inhibitory activity. Furthermore, the flexible linker and the adjacent solvent group would be favorable to stabilize the conformation and to enhance the two interactions mentioned above. Based on our patent, 14 new compounds were designed by our design strategy. The binding mode exhibited as expected and their activities were predicted by topomer CoMFA model. The preliminary biological tests showed most of them have potent activity to c‐met kinase. Our study would provide guidelines to design some new U‐shaped c‐met inhibitors with new scaffolds and optimize the current molecules.

In this study, the novel germatrane compound, 3-(2, 8, 9-trioxa-5-aza-1- germatricyclo [3.3.3.0] undecane-1- yl)-3-(4-hydroxy-3- methoxyphenyl)-propionic acid (1), has been synthesized and its activities against cervical tumor U14 were evaluated in vitro and in vivo. The results have demonstrated that the compound posed significant inhibition on U14 tumor with IC50 values of 48.57 mg/L in cell-based assay and tumor inhibitory rates of 38.50 , 47.17 and 64.02 (from low dose to high dose) in animal experiment.

Cyclic peptides represent one of the most promising therapeutic agents in drug discovery due to their good affinity and selectivity. Herein, an on-resin synthesis of aryl thioether containing peptides and a concise cyclization strategy via chemoselective cysteine SNAr reaction was developed. The arylation group could be incorporated into a series of amino acids and used for standard SPPS and peptides cyclization. Constructed cyclic peptides showed increased cellular uptakes compared to their linear peptides.

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The new germanium compounds of cinnamic acid, RC6H4CHGe(OCH2CH2)3NCH2COOH RH (I), 2-OH (II), 3-OH (III), 4-OH (IV), have been obtained to study anti-tumor activities. Compounds (I-IV) were prepared by the electrophilic addition reaction and nucleophilic substitution reaction. Biological investigation has demonstrated that all compounds (I-IV) are lower toxicity with strongly anti-tumor activity than positive control.