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Six terpyridine‑nickel complexes 1-6 were formed by the coordination of 4'-(4-R-phenyl)-2,2':6',2″-terpyridine (R = hydroxyl (L 1 ), methoxyl (L 2 ), methylsulfonyl (L 3 ), fluoro (L 4 ), bromo (L 5 ), iodo (L 6 )) derivatives to nickel nitrate. The compositions and structures of these complexes were analyzed by Fourier Transform infrared spectroscopy (FT-IR), elemental analyses, electrospray ionization mass spectra (ESI-MS), solid-state ultraviolet-visible (UV-Vis) spectroscopy, and single crystal X-ray diffraction (1, 2 and 4) studies. In vitro anticancer cell proliferation experiments against SiHa (human cervical squamous cancer cell line) cells, Bel-7402 (human hepatoma cancer cell line), Eca-109 (human esophageal cancer cell line) and HL-7702 (human normal hepatocyte cell line) indicate that they have more excellent anti-proliferation effects than the cis-platin against Siha cells, Bel-7402 cells and Eca-109 cells. Especially, complex 5 showed a rather outstanding inhibitory effect against the SiHa cell line and was less toxic than the other compounds to the HL-7702 cell line, implying an obvious specific inhibitory effect. Therefore, complex 5 has the potential value to be developed as an anticancer cell-specific drug against human cervical squamous carcinoma. Molecular docking simulation, UV-vis absorption spectroscopy and circular dichroism experiments show that they prefer to bind to DNA part in an embedded binding manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

With the aim of developing potential anticancer drug candidates, a series of Fe(II) complexes were synthesized using nine 2,2':6',2''-terpyridine ligands functionalized with substituted-phenyl groups, and their biological activities were systematically investigated. Their bis-terpyridine sandwich-like structures were determined by single crystal X-ray crystallography. In vitro antiproliferative experiments based on three human cancer cell lines, including human hepatoma cancer cell line (Bel-7402), human esophageal cancer cell line (Eca-109), and human cervical squamous cancer cell line (SiHa), indicate the high antiproliferation activities of these complexes compared with commercial cisplatin. And their toxicity to normal cells was estimated based on human normal hepatocyte (HL-7702) cell line. In particular, when the phenyl in terpyridine ligand was modified by a carboxyl group, the corresponding complex 3 exhibited much higher antiproliferation to cancer Bel-7402 cells (IC 50 = 3.653 μmol L -1 ) than cisplatin and low toxicity to normal HL-7702 cells (IC 50 = 99.92 μmol L -1 ), implying a significant selectivity for 3 in killing hepatoma cancer cells. Combined with the fact that iron element is more accessible than platin, this series of Fe(II) complexes comprises potential candidates for anticancer drugs with specific inhibition of hepatoma cancer. UV titration experiments and circular dichroism (CD) showed a strong binding affinity between these nine complexes and CT-DNA. However, molecular docking simulation revealed the competitive binding of DNA and protein to these complexes. Further, the interactions between these complexes and bovine serum albumin (BSA) have been studied by fluorescence titration and CD spectroscopy.

A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4'-(4-substituent phenyl)-2',2':6',2″-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI-MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes 3 (-methoxyl) and 7 (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC 50 values of 0.223 μM and 0.335 μM, complexes 4 and 6 showed certain cell selectivity, and complex 6 can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites., (© 2023. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

Six silver hexafluoroantimonate complexes (1-6) with 4'-(4'-substituted-phenyl)-2,2':6',2''-terpyridine compounds bearing hydrogen (L1), methyl (L2), methylsulfonyl (L3), chloro (L4), bromo (L5) and iodo (L6) were prepared and characterized by 1 H NMR, 13 C NMR, IR, elemental analysis and single crystal X-ray diffraction. All the compounds exhibit interesting photoluminescence properties in the solid state and solution. In vitro data demonstrate that all of them show higher antiproliferative activities than cisplatin against three human carcinoma cell lines, A549, Eca-109 and MCF-7. Compound 3 exhibits the lowest IC 50 value (2.298 μM) against A549 cell lines, which is 2.963 μM for 4 against Eca-109 and 1.830 μM for 1 against MCF-7. For silver halogen-substituted terpyridine compounds, their anticancer activities decrease following the sequence of -Cl, -Br, and -I substituents. The comparison results show that their anticancer activity is significantly higher than that of their free ligands. The DNA interaction was studied by fluorescence titration, circular dichroism spectroscopy and molecular modeling methods. Spectrophotometric results reveal that the compounds have strong affinity binding with DNA as intercalators and molecular docking studies indicate that the binding is contributed by the π-π stacking and hydrogen bonds. The DNA binding ability of the complexes has been correlated with their anticancer activities, which could potentially provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.

Ten new palladium(II) complexes [PdCl(L 1-10 )]Cl have been synthesized by the reaction of palladium(II) chloride and ten 4'-(substituted-phenyl)-2,2':6',2''-terpyridine ligands bearing hydrogen(L 1 ), p-hydroxyl(L 2 ), m-hydroxyl (L 3 ), o-hydroxyl (L 4 ), methyl (L 5 ), phenyl (L 6 ), fluoro (L 7 ), chloro (L 8 ), bromo (L 9 ), or iodo (L 10 ). Their structures were confirmed by FT-IR, 1 H NMR, elemental analysis and/or single crystal X-ray diffraction analysis. Their in vitro anticancer activities were investigated based on five cell lines, including four cancer cell lines (A549, Eca-109, Bel-7402, MCF-7) and one normal cell line (HL-7702). The results show that these complexes possess a strong killing effect on the cancer cells but a weak proliferative inhibition on the normal cells, implying their high inhibitory selectivity for the proliferation of the cancer cell lines. Flow cytometry characterization reveals that these complexes affect cell proliferation mainly in the G0/G1 phase and induce the late apoptotic of the cells. The quantity of palladium(II) ion in extracted DNA was determined by ICP-MS, which proved that these complexes target genomic DNA. And the strong affinity of the complexes with CT-DNA were confirmed by UV-Vis spectrum and circular dichroism (CD). The possible binding modes of the complexes with DNA were further explored by molecular docking. As the concentration of complexes 1-10 gradually increases, the fluorescence intensity of bovine serum albumin (BSA) decreases by a static quenching mechanism., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2023. Published by Elsevier Inc.)

Eleven manganese 4'-substituted-2,2':6',2″-terpyridine complexes ( 1a - 1c and 2a - 2h ) with three non-oxygen-containing substituents ( L 1a - L 1c : phenyl, naphthalen-2-yl and naphthalen-1-yl, L 1a - L 1c ) and eight oxygen-containing substituents ( L 2a - L 2h : 4-hydroxyl-phenyl, 3-hydroxyl-phenyl, 2-hydroxyl-phenyl, 4-methoxyl-phenyl, 4-carboxyl-phenyl, 4-(methylsulfonyl)phenyl, 4-nitrophenyl and furan-2-yl) were prepared and characterized by IR, elemental analysis or single crystal X-ray diffraction. In vitro data demonstrate that all of these show higher antiproliferative activities than cisplatin against five human carcinoma cell lines: A549, Bel-7402, Eca-109, HeLa and MCF-7. Compound 2d presents the strongest antiproliferative effect against A549 and HeLa cells, with IC 50 values being 0.281 μM and 0.356 μM, respectively. The lowest IC 50 values against Bel-7402 (0.523 μM) Eca-109 (0.514 μM) and MCF-7 (0.356 μM) were obtained for compounds 2h , 2g and 2c , respectively. Compound 2g with a nitro group showed the best results on the whole, with relevantly low IC 50 values against all the tested tumor cells. The DNA interactions with these compounds were studied by circular dichroism spectroscopic and molecular modeling methods. Spectrophotometric results revealed that the compounds have strong affinities in binding with DNA as intercalators, and the binding induces DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π-π stacking and hydrogen bonds. The anticancer activities of the compounds are correlated with their DNA binding ability, and the modification of oxygen-containing substituents significantly enhanced the anticancer activity, which could provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.

Eleven copper chloride coordination compounds (1-11) with 4'-(4'-substituted-phenyl)-2,2':6',2''-terpyridine ligands bearing hydrogen (L 1 ), cyano (L 2 ), p-hydroxyl (L 3 ), m-hydroxyl (L 4 ), o-hydroxyl (L 5 ), methoxyl (L 6 ), iodo (L 7 ), bromo (L 8 ), chloro (L 9 ), fluoro (L 10 ) or methylsulfonyl (L 11 ) were prepared and characterized by IR spectroscopy, elemental analysis and single crystal X-ray diffraction. Antiproliferative activities against tumor cells were investigated and DNA interactions were studied by circular dichroism spectroscopy and molecular modeling methods. In vitro data demonstrate that all the compounds exhibit higher antiproliferative activities as compared to cisplatin against five human carcinoma cell lines: A549, Bel-7402, Eca-109, HeLa and MCF-7. Compound 6 with methoxyl shows the best anti-proliferation activity. Spectrophotometric results reveal the strong affinity of the compounds for binding with DNA as intercalators and induce DNA conformational transitions. The results of molecular docking studies show that the compounds interact with DNA through π-π stacking, van der Waals forces, hydrophobic interactions and hydrogen bonds. The binding energies between compound 11 and three macromolecules, including DNA duplex, oligonucleotide and DNA-Topo I complex, are the lowest. The binding stability of compounds containing hydroxyl, methoxy and methylsulfonyl groups with biological macromolecules mainly relies on the hydrogen bonds. The ability of a compound to form hydrogen bonds can promote its binding to biological targets, thereby exhibiting high antiproliferative activity.

Poly(ADP-ribose) polymerase-1 (PARP-1), a critical DNA repair enzyme in the base excision repair pathway, has been pursued as an attractive cancer therapeutic target. Intervention with PARP-1 has been proved to be more sensitive to cancer cells carrying BRCA1/2 mutations. Several PARP-1 inhibitors have been available on market for the treatment of breast, ovarian and prostatic cancer. Promisingly, the newly developed proteolysis targeting chimaeras (PROTACs) may provide a more potential strategy based on the degradation of PARP-1. Here we report the design, synthesis, and evaluation of a proteolysis targeting chimaera (PROTAC) based on the combination of PARP-1 inhibitor olaparib and the CRBN (cereblon) ligand lenalidomide. In SW620 cells, our probe-quality degrader compound 2 effectively induced PARP-1 degradation which results in anti-proliferation, cells apoptosis, cell cycle arresting, and cancer cells migratory inhibition. Thus, our findings qualify a new chemical probe for PARP-1 knockdown.

A series of CdCl 2 complexes (1a-1f and 2a-2c) with 4'-(substituted-phenyl)-2,2':6',2″-terpyridine compounds bearing hydrogen (L 1a ), p-methyl (L 1b ), p-phenyl (L 1c ), p-tolyl (L 1d ), p-carboxyl (L 1e ), p-fluoro (L 1f ), p-hydroxyl (L 2a ), m-hydroxyl (L 2b ) or o-hydroxyl (L 2c ), were prepared and characterized by 1 H NMR, IR, elemental analysis and single crystal X-ray diffraction. All the compounds display interesting photoluminescent properties and different maximal emission peaks due to the difference of the substituent groups. The in vitro antiproliferative activities against four human carcinoma cell lines, A549, Bel-7402, Eca-109 and MCF-7, were investigated and cell viability studies indicate that the compounds have excellent results with the lowest IC 50 values of 0.372 (1c), 1.003 (1c), 1.161 (1b) and 0.231 (1c) μM, respectively. The DNA interaction was studied by fluorescence titration, circular dichroism spectroscopy and molecular modeling methods. Spectrophotometric results reveal that the compounds have strong affinity binding with DNA as intercalators and molecular docking studies indicate that the binding is contributed by the π…π stacking and hydrogen bonds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Six zinc(II) complexes, [Zn(OCOPh) 2 L R ] (R = 1, 2, 3, 4, 5, 6) were synthesized by the reaction of zinc benzoate and six para-substituted 4-phenyl-terpyridine complexes and their structures were confirmed by elemental analysis, FT-IR, 1 H NMR and X-ray single crystal diffraction analysis. Their photoluminescent properties in solid and in solutions of DMSO were studied. Three human cancer cell lines were used for antiproliferative potential: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109) and human breast cancer cell line (MCF-7). The results have shown that these zinc complexes have good inhibitory effects on cancer cells, which are better than that of the commonly used clinical drug cisplatin. The ability of the complexes to binding to CT-DNA was studied by UV spectroscopy and fluorescence titration, while the interaction between the complexes and CT-DNA, AT6, GC6 short-chain DNA sequences and G-quadruplex were analyzed by circular dichroism (CD). It is found that these complexes can bind to DNA, and the binding mode is mainly intercalator. The docking of the complexes with the DNA fragment was simulated using molecular docking software. All the results clearly display that the substituents at these ligands of the complexes have the substitution effects on the properties of photoluminescence, antiproliferative potential and DNA binding study.

Six zinc(II) complexes [Zn(Br) 2 L 1 ] (1), [Zn(Br) 2 L 2 ] (2) and [Zn(Br) 2 L 3 ] (3), [Zn(I) 2 L 1 ] (4), [Zn(I) 2 L 2 ] (5) and [Zn(I) 2 L 3 ] (6) have been obtained by the reactions of ZnBr 2 or ZnI 2 with p-hydroxyl-4'-phenyl-terpyridine(L 1 ), m-hydroxyl-4'-phenyl-terpyridine(L 2 ) and o-hydroxyl-4'-phenyl-terpyridine(L 3 ), which were characterized by elemental analysis, FT-IR and NMR, as well as single crystal X-ray diffraction. Comparing to cisplatin, compounds 1-6 show higher antiproliferative activity against human lung carcinoma cell line (A549), human ileocecal colorectal adenocarcinoma cell line (HCT-8) and human breast cancer cell line (MCF-7). As the concentration of compounds 1-6 increases in the BHb/HHb-compound system, the fluorescent intensity of bovine hemoglobin (BHb) and human hemoglobin (HHb) reduces with a static quenching mechanism. The binding constant and the number of binding sites for the interaction of the compounds with BHb and HHb were calculated. Molecular docking studies suggest that the binding process of these compounds with heat shock protein 90 (Hsp90), BHb and HHb is a spontaneous molecular interaction process, in which van der Waals forces and hydrogen bonds play major roles, and π-π interaction also has influence on binding process. These results suggest that compounds 1-6 can be candidates for further evaluation as chemotherapeutic agents against human tumor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inhibition of BET family of bromodomain is an appealing intervention strategy for several cancers and inflammatory diseases. This article highlights our work toward the identification of potent, selective, and efficacious BET inhibitors using a structure-based approach focused on improving potency. Our medicinal chemistry efforts led to the identification of compound 24, a novel phenanthridin-6(5H)-one derivative, as a potent (IC 50  = 0.24 μM) and selective BET inhibitor with excellent cancer cell lines inhibitory activities and favorable oral pharmacokinetic properties., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Reactions between halogen substituted terpyridine ligands F- (L1), Cl- (L2), Br- (L3) and I-4'-phenyl-terpyridine (L4) and ZnBr2 or ZnI2 led to the formation of complexes [Zn(Br)2L1] (1), [Zn(i)2L1] (2), [Zn(Br)2L2] (3), [Zn(i)2L2] (4), [Zn(Br)2L3] (5), [Zn(i)2L3] (6), [Zn(Br)2L4] (7), and [Zn(i)2L4] (8), respectively, which were characterized by elemental analysis, 1H NMR, IR and single crystal X-ray diffraction. Their photoluminescence properties, solution stabilities, hydrophilicity/lipophilicity properties and anti-proliferative activity against three cancer cell lines as well as structure-function relationships are analyzed. All the complexes, which show high solution stabilities and lipophilicity under determination conditions, reveal much higher antiproliferative activities than cisplatin against the human lung carcinoma cell line (A549), human hepatocellular carcinoma cell line (Bel-7042) and human breast cancer cell line (MCF-7) in vitro. Fluorescence spectroscopy and circular dichroic analysis reveal that the compounds have strong affinity binding with ctDNA and stack onto the base pairs of the ctDNA. The results obtained are further explained in terms of the electronic properties of the compounds by density functional theory (DFT) calculations, and it is found that the halogen anions play critical roles in the antitumor activity of these compounds. Their affinities to HSP90 proteins, ALK, EGFR and HER2 kinases and the binding sites on these proteins have been determined by computational docking analysis, and the results indicate that the only form of their binding is van der Waals forces.

Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4'-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.

Reactions between 4'-phenyl-terpyridine (L) and several Zn(II) salts (sulfate, nitrate, chloride or acetate) led to the formation of the complexes [Zn(2)(mu-O(2)SO(2))(2)L(2)(CH(3)OH)(2)] (1), [Zn(NO(3))L(H(2)O)]NO(3) (2), [Zn(Cl)(2)L] (3) and [Zn(CH(3)COO)(2)L] (4) which were characterized by IR, (1)H NMR and fluorescence spectroscopies, elemental analysis and single crystal X-ray diffraction. In the dinuclear molecule of 1 the Zn atom is hexacoordinated, with a N(3)O(3) coordination environment and forms an octagonal ZnOSOZnOSO metallacycle. In the remaining structures, the metal atom is envisaged as possessing highly distorted N(3)X(2) (X = O or Cl) square pyramid coordination geometries. The structure of 3 presents two different packing patterns which lead to distinct pi-pi stackings. In both structures 2 and 4, strong intermolecular hydrogen bonds were identified. The complexes exhibit promising in vitro tumor-inhibiting activities, which are higher than that of cisplatin, against the following human tumor cell lines: promyelocyticfina leukaemia (HL-60), hepatocellular carcinoma (Bel-7402), gastric carcinoma (BGC-823) and nasopharyngeal carcinoma (KB)., (2010 Elsevier Inc. All rights reserved.)

Pancreatic cancer is highly resistant to the currently available chemotherapeutic agents. Less than 5% of patients diagnosed with this disease could survive beyond 5 years. Thus, there is an urgent need for the development of novel, efficacious drugs that can treat pancreatic cancer. Herein we report the identification of artesunate (ART), a derivative of artemisinin, as a potent and selective antitumor agent against human pancreatic cancer cells in vitro and in vivo. ART exhibits selective cytotoxic activity against Panc-1, BxPC-3 and CFPAC-1 pancreatic cancer cells with IC(50) values that are 2.3- to 24-fold less than that of the normal human hepatic cells (HL-7702). The pan caspase inhibitor zVAD-fmk did not inhibit the cytotoxic activity of ART. Electron microscopy of ART-treated cells revealed severe cytoplasmic swelling and vacuolization, swollen and internally disorganized mitochondria, dilation (but not fragmentation) of the nuclei without chromatin condensation, and cell lysis, yielding a morphotype that is typical of oncosis. The ART-treated cells exhibited a loss of mitochondrial membrane potential (DeltaPsim) and ART-induced cell death was inhibited in the presence of the reactive oxygen species (ROS) scavenger N-acetyl-cysteine (NAC). Importantly, ART produced a dose-dependent tumor regression in an in vivo pancreatic cancer xenografts model. The in vivo antitumor activity of ART was similar to that of gemcitabine. Taken together, our study suggests that ART exhibits antitumor activity against human pancreatic cancer via a novel form of oncosis-like cell death, and that ART should be considered a potential therapeutic candidate for treating pancreatic cancer.

Artemisinin and its analogue dihydroartemisinin exert cytotoxic effects in some kinds of cancer cell lines. Here we determined whether dihydroartemisinin inhibits the growth and induces apoptosis of rat C6 glioma cells. We found dihydroartemisinin (5-25 microM) inhibited the growth and induced apoptosis of C6 cells in a concentration- and time-dependent manner; however, it was much less toxic to rat primary astrocytes. Dihydroartemisinin (5-25 microM) also increased the generation of reactive oxygen species in C6 cells. These effects of dihydroartemisinin were enhanced by ferrous ions (12.5-100 microM) and reduced by the iron chelator deferoxamine (25-200 microM). Immunoblotting analysis revealed that dihydroartemisinin (5-25 microM) significantly reduced hypoxia- and deferoxamine-induced expression of hypoxia inducible factor-1alpha and its target gene protein, vascular endothelial growth factor, in C6 cells. The results showed that dihydroartemisinin exerts a selective cytotoxic effect on C6 cells by increasing the reactive oxygen species and inhibiting hypoxia inducible factor-1alpha activation.

The reactions of copper chloride and 4′-(4′-substituted-phenyl)-2,2′:6′,2′′-terpyridine ligands bearing nitro (L1), methyl (L2), phenyl (L3), tolyl (L4) and carboxyl (L5) gave five copper compounds (1–5) which have mononuclear structures with their Cu(II) ions five-coordinate in the irregular square pyramidal geometries. Their in vitro biological properties were evaluated by CCK-8 assay, which show remarkable proliferation inhibitive properties on the cancer cell lines including A549, Eca-109, and Bel-7402, and two human normal cell lines (HL-7702 and HLF). The values of IC50 indicate better anticancer activities of these compounds than that of cisplatin. Compound 2 with methyl group exhibits the best anticancer activity, with IC50 value < 2.5 µM on all the tested cancer cells. The interactions of the compounds with DNA were evaluated using UV–Vis absorption titrations, circular dichroism spectroscopy, and DNA viscosity. The complexes show significant insertion binding with DNA sequences and strong intercalator binding mode with DNA sequences. Compounds 1–5 interact with the functional groups of DNA through π···π stacking, van der Waals interactions, hydrophobic interactions, and hydrogen bonds as determined by molecular docking. In addition, strong binding interactions between the five copper(II) complexes and bovine serum albumin (BSA) were studied by fluorescence titration and circular dichroism spectroscopy. [ABSTRACT FROM AUTHOR]

A series of open-chain analogs of cyclic peptides was designed and synthesized using sansalvamide A as a model compound. All compounds exhibited low antitumor activity. Furthermore, the evaluation of their inhibitory potency toward IMPDH, SHP2, ACHE, proteasome, MAGL, and cathepsin B showed that all of the compounds were potent against protein tyrosine phosphatase Shp2. Specifically, compounds 1a , 1d , 2b , and 2f were found to inhibit SHP2 with IC 50 values in the low micromolar range and good selectivity. Based on the molecular docking results, the binding modes of the chain cyclic peptides in the active center of SHP2 were discussed. [ABSTRACT FROM AUTHOR]