Novel Symmetrical trans‐Bis‐Schiff Bases of N‐Substituted‐4‐ piperidones: Synthesis,Characterization, and Preliminary Antileukemia Activity Mensurations

A series of novel symmetrical trans‐bis‐Schiff bases ( 11a , 11b , 11c , 11d , 11e , 11f , 11g , 11h , 11i , 11j , 11k , 11l , 11m ) were designed and prepared as novel anticancer analogues, with the trans‐configuration confirmed by X‐ray diffraction. Preliminary inhibitory effects of these compounds on CML K562 cell growth were investigated, and the potential analogue 11e showed an excellent anti‐leukemia activity (IC₅₀=6.35 μg/mL), which is higher than that of the clinical drug 5‐fluorouracil (IC₅₀=8.48 μg/mL). Complete assignments had been achieved for the title compounds by spectroscopic techniques, and their structure–activity relationships have been studied.     

Efficient Synthesis of Pyrrolo [2,3‐d] Pyrimidines Containing 1,4‐Disubstituted‐1,2,3‐Triazole Derivatives

Here, we demonstrate a simple but highly efficient method for the synthesis of multifunctionalized pyrrolo[2,3‐d]pyrimidines containing 1,4‐disubstituted 1,2,3‐triazole derivative coupled with various amines ( 10a , 10b , 10c , 10d , 10e , 10f , 10g ) and alcohol ( 10h ) to obtain final compounds ( 11a , 11b , 11c , 11d , 11e , 11f , 11g , 11h ) with reasonable to excellent yields (25% to 94%). The newly synthesized compounds were characterized by IR, ¹HNMR, ¹³CNMR, and mass spectroscopy analysis.     

Rapid ‘on-column’ preparation of hydrogen [11C]cyanide from [11C]methyl iodide via [11C]formaldehyde

Hydrogen [¹¹C]cyanide ([¹¹C]HCN) is a versatile ¹¹C-labelling agent for the production of ¹¹C-labelled compounds used for positron emission tomography (PET). However, the traditional method for [¹¹C]HCN production requires a dedicated infrastructure, limiting accessibility to [¹¹C]HCN. Herein, we report a simple and efficient [¹¹C]HCN production method that can be easily implemented in ¹¹C production facilities. The immediate production of [¹¹C]HCN was achieved by passing gaseous [¹¹C]methyl iodide ([¹¹C]CH₃I) through a small two-layered reaction column. The first layer contained an N-oxide and a sulfoxide for conversion of [¹¹C]CH₃I to [¹¹C]formaldehyde ([¹¹C]CH₂O). The [¹¹C]CH₂O produced was subsequently converted to [¹¹C]HCN in a second layer containing hydroxylamine-O-sulfonic acid. The yield of [¹¹C]HCN produced by the current method was comparable to that of [¹¹C]HCN produced by the traditional method. The use of oxymatrine and diphenyl sulfoxide for [¹¹C]CH₂O production prevented deterioration of the molar activity of [¹¹C]HCN. Using this method, compounds labelled with [¹¹C]HCN are now made easily accessible for PET synthesis applications using readily available labware, without the need for the ‘traditional’ dedicated cyanide synthesis infrastructure.

In a reaction column, gaseous [¹¹C]methyl iodide was converted to [¹¹C]formaldehyde in a first layer containing N-oxide and then transformed into hydrogen [¹¹C]cyanide in a second layer containing hydroxylamine-O-sulfonic acid within 2 minutes.     

Undecahalo‐closo‐undecaborates [B11Hal11]2–

The closo‐undecaborate A₂[B₁₁H₁₁] (A = NBzlEt₃) can be halogenated with excess N‐chlorosuccine imide, bromine or iodine, respectively, to give the perhalo‐closo‐undecaborates A₂[B₁₁Hal₁₁] (Hal = Cl, Br, I). The chlorination in the 11 : 1 ratio of the reagents yields A₂[B₁₁HCl₁₀], whose subsequent iodination makes A₂[B₁₁Cl₁₀I] available. The three type [B₁₁Hal₁₁]^2– anions show only one and the two type [B₁₁Cl₁₀X]^2– anions (X = H, I) only two ¹¹B NMR peaks in the ratio 10 : 1, thus exhibiting the same degenerate rearrangement of the octadecahedral B₁₁ skeleton as is well‐known for [B₁₁H₁₁]^2–. The crystal structure analysis of A₂[B₁₁Br₁₁] and A₂[B₁₁I₁₁] reveals a rigid octadecahedral skeleton in the solid state, up to 330 K, whose B–B bond lengths deviate more or less from the idealized C_2v gas phase structure, but are in good accordance with the distances of A₂[B₁₁H₁₁]. Electrochemical experiments elucidate the mechanism of the known oxidation of [B₁₁H₁₁]^2– to give [B₂₂H₂₂]^2–: A first one‐electron transfer is followed by the dimerization of the [B₁₁H₁₁]^– monoanion, whereas neutral B₁₁H₁₁, a presumably most reactive species, does not play a role as an intermediate. The electrochemical oxidation of [B₁₁Hal₁₁]^2– anions also starts with a one‐electron transfer, which is perfectly reversible only in the case of Hal = Br. There is no electrochemical indication for the formation of [B₂₂Hal₂₂]^2–. The neutral species B₁₁Hal₁₁ should be a short‐lived, very reactive species.     

Expression and Characterization of Hyperthermotolerant Xylanases,SyXyn11P and SyXyn11E,in Pichia pastoris and Escherichia coli

Both Syxyn11P and Syxyn11E, two codon-optimized genes encoding glycoside hydrolase (GH) family 11 hyperthermotolerant xylanases (designated SyXyn11P and SyXyn11E), were synthesized and inserted into pPIC9K^M and pET-28a(+) vectors, respectively. The resulting recombinant expression vectors, pPIC9K^M-Syxyn11P and pET-28a(+)-Syxyn11E, were transformed into Pichia pastoris GS115 and Escherichia coli BL21, respectively. The maximum activities of two recombinant xylanases (reSyXyn11P and reSyXyn11E) expressed in P. pastoris and E. coli reached 30.9 and 17.8 U/ml, respectively. The purified reSyXyn11P and reSyXyn11E displayed the same pH optimum at 6.5 and pH stability at a broad range of 4.5–9.0. The temperature optimum and stability of reSyXyn11P were 85 and 80 °C, higher than those of reSyXyn11E, respectively. Their activities were not significantly affected by metal ions tested and EDTA, but strongly inhibited by Mn²⁺ and Ag⁺. The K _m and V _max of reSyXyn11P toward birchwood xylan were 4.3 mg/ml and 694.6 U/mg, whose K _m was close to that (4.8 mg/ml), but whose V _max was much higher than that (205.6 U/mg) of reSyXyn11E. High-performance liquid chromatography analysis indicated that xylobiose and xylotriose as the major products were excised from insoluble corncob xylan by reSyXyn11P.     

Similar sequences but dissimilar biological functions of GDF11 and myostatin

Growth differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related TGFβ family members that are often believed to serve similar functions due to their high homology. However, genetic studies in animals provide clear evidence that they perform distinct roles. While the loss of Mstn leads to hypermuscularity, the deletion of Gdf11 results in abnormal skeletal patterning and organ development. The perinatal lethality of Gdf11-null mice, which contrasts with the long-term viability of Mstn-null mice, has led most research to focus on utilizing recombinant GDF11 proteins to investigate the postnatal functions of GDF11. However, the reported outcomes of the exogenous application of recombinant GDF11 proteins are controversial partly because of the different sources and qualities of recombinant GDF11 used and because recombinant GDF11 and MSTN proteins are nearly indistinguishable due to their similar structural and biochemical properties. Here, we analyze the similarities and differences between GDF11 and MSTN from an evolutionary point of view and summarize the current understanding of the biological processing, signaling, and physiological functions of GDF11 and MSTN. Finally, we discuss the potential use of recombinant GDF11 as a therapeutic option for a wide range of medical conditions and the possible adverse effects of GDF11 inhibition mediated by MSTN inhibitors.Subject terms: Growth factor signalling, Transforming growth factor beta, Evolutionary biology     

Substituting Both the N-Terminal and “Cord” Regions of a Xylanase from <Emphasis Type="Italic">Aspergillus oryzae</Emphasis> to Improve Its Temperature Characteristics

To improve the temperature characteristics of AoXyn11A, a mesophilic glycoside hydrolase family (GHF) 11 xylanase from Aspergillus oryzae CICC40186, its N-terminal and “cord” regions were selected to be substituted by means of the computer-aided analysis and calculation. In brief, one mutant, named ATX11A⁴¹, possessing the lowest root-mean-square deviation (RMSD) value was designed based on the molecular dynamics (MD) simulation by substituting the N-terminal 41 amino acids of AoXyn11A with the corresponding 42 ones of pXYL11, a thermophilic GHF11 xylanase from Thermobifida fusca. On the basis of the primary structure alignment of pXYL11 with ATX11A⁴¹ (or AoXyn11A), another mutant, named ATX11A^41/cord, was designed by substituting the cord region (⁹³GTYNPGSGG¹⁰¹) of ATX11A⁴¹ with the corresponding one (⁹³GTYRPTG⁹⁹) of pXYL11. Both mutant-encoding genes, ATx11A⁴¹ and ATx11A^41/cord, were constructed as designed theoretically by a megaprimer PCR technique and were expressed in Pichia pastoris GS115. The specific activities of recombinant (re) AoXyn11A, ATX11A⁴¹, and ATX11A^41/cord were 2916.7, 2667.6, and 2457.0 U/mg, respectively. The analysis of temperature characteristics displayed that the temperature optimum (T_opt) of reATX11A⁴¹ or reATX11A^41/cord was 65 °C, which was 15 °C higher than that of reAoXyn11A. The thermal inactivation half-life (t_1/2) values of reATX11A⁴¹ and reATX11A^41/cord at 60 °C were 55 and 83 min, respectively, whereas that of reAoXyn11A was only 18 min at 50 °C. The melting temperature (T_m) values of reAoXyn11A, reATX11A⁴¹, and reATX11A^41/cord were 54.2, 66.7, and 71.9 °C, respectively. In conclusion, the above findings indicated that the substitution of both the N-terminal and cord regions of a mesophilic AoXyn11A greatly contributed to its improved temperature characteristics.     

A short and efficient synthesis of 11-deoxyanthracyclinones: strong base-induced cycloaddition of the suitably substituted tetrahydrohomophthalic anhydride

The preparation and use of the suitably substituted tetrahydrohomophthalic anhydride ($\text{17}$) as a common intermediate for a short regiospecific synthesis of 11-deoxyanthracyclinones, 11-deoxydaunomycinone ($\text{11}$), 11-deoxy-carminomycinone ($\text{12}$), and 4-demethoxy-11-deoxydaunomycinone ($\text{13}$) is described.     

Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics

Aldosterone is synthesised by aldosterone synthase (CYP11B2). CYP11B2 has a highly homologous isoform, steroid 11β-hydroxylase (CYP11B1), which is responsible for the biosynthesis of aldosterone precursors and glucocorticoids. To investigate aldosterone biosynthesis and facilitate the search for selective CYP11B2 inhibitors, we constructed three-dimensional models for CYP11B1 and CYP11B2 for both human and rat. The models were constructed based on the crystal structure of Pseudomonas Putida CYP101 and Oryctolagus Cuniculus CYP2C5. Small steric active site differences between the isoforms were found to be the most important determinants for the regioselective steroid synthesis. A possible explanation for these steric differences for the selective synthesis of aldosterone by CYP11B2 is presented. The activities of the known CYP11B inhibitors metyrapone, R-etomidate, R-fadrazole and S-fadrazole were determined using assays of V79MZ cells that express human CYP11B1 and CYP11B2, respectively. By investigating the inhibitors in the human CYP11B models using molecular docking and molecular dynamics simulations we were able to predict a similar trend in potency for the inhibitors as found in the in vitro assays. Importantly, based on the docking and dynamics simulations it is possible to understand the enantioselectivity of the human enzymes for the inhibitor fadrazole, the R-enantiomer being selective for CYP11B2 and the S-enantiomer being selective for CYP11B1.     

Synthesis of Novel Biologically Active Proflavine Ureas Designed on the Basis of Predicted Entropy Changes

A novel series of proflavine ureas, derivatives 11a–11i, were synthesized on the basis of molecular modeling design studies. The structure of the novel ureas was obtained from the pharmacological model, the parameters of which were determined from studies of the structure-activity relationship of previously prepared proflavine ureas bearing n-alkyl chains. The lipophilicity (LogP) and the changes in the standard entropy (ΔS°) of the urea models, the input parameters of the pharmacological model, were determined using quantum mechanics and cheminformatics. The anticancer activity of the synthesized derivatives was evaluated against NCI-60 human cancer cell lines. The urea derivatives azepyl 11b, phenyl 11c and phenylethyl 11f displayed the highest levels of anticancer activity, although the results were only a slight improvement over the hexyl urea, derivative 11j, which was reported in a previous publication. Several of the novel urea derivatives displayed GI₅₀ values against the HCT-116 cancer cell line, which suggest the cytostatic effect of the compounds azepyl 11b–0.44 μM, phenyl 11c–0.23 μM, phenylethyl 11f–0.35 μM and hexyl 11j–0.36 μM. In contrast, the novel urea derivatives 11b, 11c and 11f exhibited levels of cytotoxicity three orders of magnitude lower than that of hexyl urea 11j or amsacrine.     

Synthesis and Anticancer Activity of 1,2,3-Triazole Fused N-Arylpyrazole Derivatives

A novel series of triazole derivatives 11a–11j is synthesized. Structures of the products are confirmed by ¹H and ¹³C NMR, and mass spectral data. The anticancer activities of compounds 11a–11j are evaluated against three human cancer cell lines (MCF-7, A549, and A375) using the standard MTT assay in vitro, using doxorubicin as the positive control. All the compounds exhibit significant activity against cancer cell lines. The compounds 11a, 11d, 11e, 11g, and 11j demonstrate more potent activity than the positive control.

     

Photochromic chiral liquid crystalline systems containing spiro-oxazine with a chiral substituent I. Synthesis and characterization of compounds

Photochromic acrylates containing both biphenylene and spiro-oxazine moieties with a chiral substituent and the related polymers were prepared and yielded photochromic chiral liquid crystalline systems. The photochromic acrylates containing both an undecamethylene group and a (2S, 3S)-2-chloro-3-methylpentanoyloxy group (A11SOP) or a (-)-menthoxyacetoxy group (A11SOM) gave a supercooled mesophase; the latter reflected right-handed visible light (blue colour) at room temperature. On the other hand, the photochromic acrylate containing both the (R)-(-)-2-methylpropylene and (2S, 3S)-2-chloro-3-methylpentanoyloxy groups (A3SOP) showed no mesophase. The related homopolymers, PA11SOP and PA11SOM, did not exhibit mesophases because of steric hindrance between the side groups of the polymers. However, only PA11SOM exhibited shear-induced birefringence under 100-104°C. Several copolymers consisting of the nematogenic monomer, 4-[4-(6-acryloyloxyhexyloxy)benzoyloxy]benzonitrile (A6CN), and A11SOP or A11SOM possessed a smectic phase due to reduction of the steric hindrance between the potentially smectogenic A11SOP or A11SOM moieties.     

Amide derivatives of 4-azaindole: Design,synthesis, and EGFR targeting anticancer agents

Abstract

A series of amide derivatives of azaindole-oxazoles (11a-n) were designed and synthesized and their structures were confirmed by ¹HNMR, ¹³CNMR and mass spectral analysis. Further, these derivatives were screened for their anticancer activity against human cancer cell lines viz; MCF7 (breast), A549 (lung) and A375 (melanoma). In vitro anticancer activity screening indicated that most of the hybrids exhibited potent inhibitory activities in a variety of cancer cell lines. Among the compounds 11d, 11e, 11f, 11j, 11k, 11l, 11m, and 11n were exhibited more potent activity than standard, in those mainly two compounds 11m and 11j were exhibited excellent activity in MCF-7 cell line with IC₅₀ values 0.034 and 0.036?µM. Moreover, all these compounds were carried out their molecular docking studies on EGFR receptor results indicated that two potent compounds 11m and 11j were strongly binds to protein EGFR (PDB ID: 4hjo). It was found that the energy calculations were in good agreement with the observed IC₅₀ values.     

Molecular engineering of liquid crystal polymers by living polymerization. II. Living cationic polymerization of 11-[(4-cyano-4′-biphenyl) oxy] undecanyl vinyl ether and the mesomorphic behavior of the resulting polymers

The synthesis and living cationic polymerization of 11-[(4-cyano-4′-biphenyl)oxy]-undecanyl vinyl ether ( 6 – 11 ) are described. The mesomorphic phase behavior of poly( 6 – 11 ) with different degrees of polymerization was compared to that of 6 – 11 and of 11-[(4-cyano-4′-biphenyl) oxy] undecanyl ethyl ether ( 8 – 11 ) which is the model compound of the monomeric structural unit of poly( 6 – 11 ). 6 – 11 displays a monotropic S_A and a monotropic nematic mesophase while 8 – 11 an enantiotropic S_A mesophase. Poly( 6 – 11 ) with low degrees of polymerization exhibits an enantiotropic S_A mesophase. Poly( 6 – 8 ) with high degrees of polymerization displays an enantiotropic S_X (i. e., an unidentified smectic phase) and an enantiotropic S_C mesophase. These results demonstrate that the transformation of the nematic mesophase of the monomer into a smectic mesophase after polymerization, occurs at the level of monomeric structural unit.     

Radiosynthesis of New Carbon-11-labeled Nimesulide Analogs as Potential PET SAER Tracers for Imaging of Aromatase Expression in Breast Cancer

Carbon-11-labeled nimesulide analogs, N-[¹¹C]methyl-N-(2-benzyloxy-4-nitrophenyl)methanesulfonamide ([¹¹C]4a), N-[¹¹C]methyl-N-[2-(4′-methylbenzyloxy)-4-nitrophenyl]methanesulfonamide ([¹¹C]4b), N-[¹¹C]methyl-N-[2-(4′-fluorobenzyloxy)-4-nitrophenyl]methanesulfonamide ([¹¹C]4c), N-[¹¹C]methyl-N-[2-(4′-nitrobenzyloxy)-4-nitrophenyl]methanesulfonamide ([¹¹C]8a), N-[¹¹C]methyl-N-[2-(β-naphthylmethoxy)-4-nitrophenyl]methanesulfonamide ([¹¹C]8b), and N-[¹¹C]methyl-N-[2-(2′-phenylbenzyloxy)-4-nitrophenyl]methanesulfonamide ([¹¹C]8c), have been synthesized as new potential positron emission tomography (PET) selective aromatase expression regulator (SAER) radiotracers for imaging of aromatase expression in breast cancer. The target tracers were prepared by N-[¹¹C]methylation of their corresponding precursors using [¹¹C]CH₃OTf under basic conditions (NaH) and isolated by reversed-phase high-pressure liquid chromatography (HPLC) method in 30–50% radiochemical yields decay corrected to end of bombardment (EOB) with 25–30 min overall synthesis time and 111–148 GBq/μmol specific activity at end of synthesis (EOS).     

Zur borbestimmung in silizium und germanium durch aktivierung mit protonen und deuteronen

The determination of boron via the nuclear reaction ¹¹B(p,n)¹¹C was studied in detail; the nitrogen reaction ¹⁴N(p,a)¹¹C interferes. Nitrogen also interferes deuteron activation via the nuclear reactions 10B(d,n)¹¹C and ¹¹B(d,2n)¹¹C, this interference must be attributed to the nuclear reaction ¹⁴(d,αn)¹¹C. Both interferences were investigated quantitatively. The conditions for the accurate determination of boron and for a simultaneous determination of boron and nitrogen by proton activation were established. An analytical method with chemical separation of the radioisotope ¹¹C was developed for silicon and germanium.     

General Method for the 11C‐Labeling of 2‐Arylpropionic Acids and Their Esters: Construction of a PET Tracer Library for a Study of Biological Events Involved in COXs Expression

Cyclooxygenase (COX) is a critical enzyme in prostaglandin biosynthesis that modulates a wide range of biological functions, such as pain, fever, and so on. To perform in vivo COX imaging by positron emission tomography (PET), we developed a method to incorporate ¹¹C radionuclide into various 2‐arylpropionic acids that have a common methylated structure, particularly among nonsteroidal anti‐inflammatory drugs (NSAIDs). Thus, we developed a novel ¹¹C‐radiolabeling methodology based on rapid C‐[¹¹C]methylation by the reaction of [¹¹C]CH₃I with enolate intermediates generated from the corresponding esters under basic conditions. One‐pot hydrolysis of the above [¹¹C]methylation products also allows the synthesis of desired ¹¹C‐incorporated acids. We demonstrated the utility of this method in the syntheses of six PET tracers, [¹¹C]Ibuprofen, [¹¹C]Naproxen, [¹¹C]Flurbiprofen, [¹¹C]Fenoprofen, [¹¹C]Ketoprofen, and [¹¹C]Loxoprofen. Notably, we found that their methyl esters were particularly useful as proradiotracers for a study of neuroinflammation. The microPET studies of rats with lipopolysaccharide (LPS)‐induced brain inflammation clearly showed that the radioactivity of PET tracers accumulated in the inflamed region. Among these PET tracers, the specificity of [¹¹C]Ketoprofen methyl ester was demonstrated by a blocking study. Metabolite analysis in the rat brain revealed that the methyl esters were initially taken up in the brain and then underwent hydrolysis to form pharmacologically active forms of the corresponding acids. Thus, we succeeded in general ¹¹C‐labeling of 2‐arylpropionic acids and their methyl esters as PET tracers of NSAIDs to construct a potentially useful PET tracer library for in vivo imaging of inflammation involved in COXs expression.     

Microwave‐Assisted Synthesis of Bis(enaminoketones): Versatile Precursors for Novel Bis(pyrazoles) via Regioselective 1,3‐Dipolar Cycloaddition with Nitrileimines

Synthesis of bis(enaminones) 6a , 6b , 6c and 7a , 7b , 7c was accomplished by the reaction of bis(acetophenones) 3a , 3b , 3c and 4a , 4b , 4c with dimethylformamide–dimethylacetal, under microwave irradiation. 1,3‐Dipolar cycloaddition of bis(enaminones) 6a and 7b , 7c with nitrileimines in refluxing benzene led to the regioselective synthesis of the novel bis(pyrazoles) 11a , 11b , 11c , 11d , 11e , 11f , 11g , 11h in 62–89% yield. The bis(pyrazoles) 11b , 11c underwent condensation with hydrazine hydrate to give the corresponding bis(pyrazolo[3,4‐d]pyridazines) 14a , 14b in good yields.     

Diterpenoide Chinomethane,vinyloge Chinone und ein Phyllocladan-Derivat aus Plectranthus purpuratus HARV. (Labiatae)

Diterpenoids from Leaf Glands of Plectranthus purpuratus: p-Quinomethanes, Extended Quinones, p-Acylcatechols and a Novel Phyllocladanon Derivative From the complex mixture of terpenoids from the title plant, the following novel diterpenoids have been isolated: 11-hydroxy-19-(3-methyl-2-butenoyloxy)- and 11-hydroxy-19-(3-methylbutanoyloxy)-5,7,9 (11), 13-abietatetraen-12-one ( 1a / 1b ), 11-hydroxy-19-(3-methyl-2-butenoyloxy)- and 11-hydroxy-19-(3-methylbutanoyl-oxy)-7,9(11), 13-abietatrien-6,12-dione ( 2a / 2b ), 6α, 11-dihydroxy-19-(3-methyl-2-butenoyloxy)- and 6α, 11 -dihydroxy-19-(3-methylbutanoyloxy)-7,9 (11), 13-abieta-trien-12-one ( 3a / 3b ), 11,12-dihydroxy-19-(3-methyl-2-butenoyloxy)- and 11,12-di-hydroxy-19-(3-methylbutanoyloxy)-8,11,13-abietatrien-7-one ( 4a / 4b ), and (16R)-17,19-diacetoxy-16-hydroxy-13β-kauran-3-one (=(16R)-17,19-diacetoxy-16-hydro-xyphyllocladan-3-one; 10 ). Compounds 2 and 3 are derivates of taxodione and taxodone, respectively, 4 is a derivative of cryptojaponol. The structure of 10 is Wised on a single-crystal- X -ray analysis and CD . data.     

Kallikrein-11, in Association with Coiled-Coil Domain Containing 25, as a Potential Prognostic Marker for Cholangiocarcinoma with Lymph Node Metastasis

Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes. Currently, the treatment and prognosis for CCA are mostly poor. Recently, we have reported that coiled-coil domain containing 25 (CCDC25) protein level in the sera may be a diagnostic marker for CCA. Subsequently, we identified three binding proteins of CCDC25 and found that kallikrein-11 (KLK11) expression was highest among those binding proteins. In this study, we investigated CCDC25 and KLK11 expression in CCA and adjacent normal tissues (n = 18) using immunohistochemistry. The results demonstrated that the expressions of CCDC25 and KLK11 in CCA tissues were both significantly higher than the adjacent tissues (p < 0.001 and p = 0.001, respectively). Then, using GEPIA bioinformatics analysis, KLK11 mRNA was significantly overexpressed in CCA tumor tissues compared with normal tissues (p < 0.05). Moreover, CCDC25 expression was positively correlated with KLK11 expression in CCA with lymph node metastasis (p = 0.028, r = 0.593). An analysis for the interaction of KLK11 with CCDC25 and other proteins, using STRING version 11.0, revealed that CCDC25 and KLK11 correlated with metastasis-related proteins. In addition, Kaplan-Meier survival curve analysis revealed that a high expression of KLK11 was associated with the poor prognosis of CCA. In conclusion, KLK11 is, as a binding protein for CCDC25, possibly involved in the metastatic process of CCA. KLK11 may be used as a prognostic marker for CCA.