Series Of Quinoline Derivatives Research Articles

Exploring the antitumor potential of novel quinoline derivatives via tubulin polymerization inhibition in breast cancer; design, synthesis and molecular docking.

A series of quinoline derivatives was designed and synthesized as novel tubulin inhibitors targeting the colchicine binding site. All the rationalized compounds 3a-e, 4a-e, 5a-e, and 6a-e have been chosen for screening their cytotoxic activity against 60 cell lines by NCI. Compounds 3b, 3c, 4c, 5c and 6c demonstrated the most notable antitumor activity against almost all cell lines. Compound 4c emerged as the most potent compound as an antiproliferative agent. This compound was subsequently chosen for five-dose testing and it exhibited remarkable broad-spectrum efficacy with strong antitumor activity against several cell lines. Compound 4c significantly induced cell cycle arrest in MDA-MB-231 cells at G2 and M phases where the cell population increased dramatically to 22.84% compared to the untreated cells at 10.42%. It also increased the population in MDA-MB-231 cells at both early and late stages of apoptosis. Compound 4c can successfully inhibit tubulin polymerization with an IC50 value of 17 ± 0.3 μM. The β-tubulin mRNA levels were notably reduced in MDA-MB-231 cells treated with compound 4c which is similar to the effect observed with colchicine treatment. Docking studies revealed that compound 4c interacted well with crucial amino acids in the active site.

New 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazoline and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinoline Derivatives: Synthesis and Biological Evaluation as Novel Anticancer Agents by Targeting G-Quadruplex.

The syntheses of novel 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazolines 12 and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinolines 13 are reported here in six steps starting from various halogeno-quinazoline-2,4-(1H,3H)-diones or substituted anilines. The antiproliferative activities of the products were determined in vitro against a panel of breast (MCF-7 and MDA-MB-231), human adherent cervical (HeLa and SiHa), and ovarian (A2780) cell lines. Disubstituted 6- and 7-phenyl-bis(3-dimethylaminopropyl)aminomethylphenyl-quinazolines 12b, 12f, and 12i displayed the most interesting antiproliferative activities against six human cancer cell lines. In the series of quinoline derivatives, 6-phenyl-bis(3-dimethylaminopropyl)aminomethylphenylquinoline 13a proved to be the most active. G-quadruplexes (G4) stacked non-canonical nucleic acid structures found in specific G-rich DNA, or RNA sequences in the human genome are considered as potential targets for the development of anticancer agents. Then, as small aza-organic heterocyclic derivatives are well known to target and stabilize G4 structures, their ability to bind G4 structures have been determined through FRET melting, circular dichroism, and native mass spectrometry assays. Finally, telomerase inhibition ability has been also assessed using the MCF-7 cell line.

Structural Simplification of Cryptolepine to Obtain Novel Antifungal Quinoline Derivatives against Phytopathogenic Fungi.

A series of quinoline derivatives were designed and synthesized by the structural simplification of cryptolepine and evaluated for their fungicidal activity against six phytopathogenic fungi. Most of these compounds exhibited remarkable activities against Botrytis cinereain vitro. Among them, compounds A18 and L01 showed superior antifungal activity. Significantly, compared to cryptolepine, compound A18 exhibited broad-spectrum inhibitory activities against B. cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani, Phytophthora capsica, Magnaporthe oryzae, and Fusarium graminearum with the respective EC50 values of 0.249, 1.569, 3.915, 0.505, 0.246, and 4.999 μg/mL. Compound L01 displayed the best antifungal activity against B. cinerea with an EC50 value of 0.156 μg/mL. Preliminary mechanistic studies showed that compound A18 could inhibit spore germination, affect the permeability of the cell membrane, increase the content of reactive oxygen species, and affect the morphology of hyphae and cells. Moreover, compound A18 showed excellent in vivo protective effect against B. cinerea, which was more potent than pyrimethanil and equitant to cryptolepine. These results evidenced that compound A18 displayed superior fungicidal activities and could be a potential fungicidal candidate against plant fungal diseases.

BIOLOGICAL ACTIVITY AND DRUG LIKE SCORE OF NEW SYNTHESIZED QUINOLINE DERIVATIVES INCORPORATED WITH PYRIDINE AND 1,3,4 - THIADIAZOLE MOIETY

A new series of quinoline derivatives has been synthesized by two different methods. In the first methods, 6-subtituted 2-(pyridin-3/4-yloxy) quinoline-3-carbaldehyde 2 was reduced with NaBH4 in methanol and then reacted with thionylchloride in DMC to give 3 which on chloramines coupling with 1,3,4 thiadiazole derivatives to give final compounds 5a-l. In the second methods, 6-substituted 2-(pyridin-3/4-yloxy) quinoline-3-carbaldehyde formed Schiff base 4 with 1,3,4 thiadiazole derivatives which on reduction with NaBH4 in DMC give 5a-l as final compounds. The synthesized compounds were confirmed for their structure by IR, 13C NMR, 1 H NMR and mass spectroscopic methods. All the synthesized compounds were evaluated for antimicrobial activity and their bioactivity score determined by Molinspiration cheminformatics software. From all the compounds, 5b, 5h and 5l have shown significant activity as compared to standard drugs.

In silico design, synthesis and anti-HIV activity of quinoline derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs)

A series of quinoline derivatives has been designed, synthesized and screened for their anti-HIV properties. The drug-like properties of compounds were evaluated first and then molecular docking using DS v20.1.0.19295 software showed that the compounds behaved as non-nucleoside reverse transcriptase inhibitors (NNRTIs) while interacting at the allosteric site of target HIV-RT protein (PDB:3MEC). The docking results revealed that all compounds formed hydrogen bonds with Lys101, Lys103, Val179, Tyr188, Gln190, Gly190, Pro225, Phe227, and Tyr318, and showed π-interaction with Tyr188 and Tyr318. TOPKAT (Toxicity Prediction by Komputer Assisted Technology) results confirmed that the compounds were found to be less toxic than the reference drugs. Density functional theory (DFT) analysis was performed to assess the binding affinity of all compounds. Further, molecular dynamics (MD) simulations were performed on compound 6 and delavirdine with HIV-RT enzyme. Comprehensive MD analyses showed a similar pattern of conformational stability and flexibility in both the complexes suggesting alike inhibitory action. The hydrogen-bonding interactions and the binding energy of active-site residues for the compound 6 complex revealed strong inhibitory activity than the reference (delavirdine) complex. Thus, the compound 6 might act as a potential inhibitor against HIV-RT. Overall, this study revealed that compound 6 (5-hydroxy-N-(4-methyl-2-oxo-1,2-dihydroquinolin-8-yl) thiophene-2-sulfonamide) has prudent anti-HIV activity against both HIV-1 (SI = 2.65) and HIV-2 (SI = 2.32) that can further be utilised in drug discovery against HIV virus.

Synthesis of new series of quinoline derivatives with insecticidal effects on larval vectors of malaria and dengue diseases

Mosquito borne diseases are on the rise because of their fast spread worldwide and the lack of effective treatments. Here we are focusing on the development of a novel anti-malarial and virucidal agent with biocidal effects also on its vectors. We have synthesized a new quinoline (4,7-dichloroquinoline) derivative which showed significant larvicidal and pupicidal properties against a malarial and a dengue vector and a lethal toxicity ranging from 4.408 µM/mL (first instar larvae) to 7.958 µM/mL (pupal populations) for Anopheles stephensi and 5.016 µM/mL (larva 1) to 10.669 µM/mL (pupae) for Aedes aegypti. In-vitro antiplasmodial efficacy of 4,7-dichloroquinoline revealed a significant growth inhibition of both sensitive strains of Plasmodium falciparum with IC50 values of 6.7 nM (CQ-s) and 8.5 nM (CQ-r). Chloroquine IC50 values, as control, were 23 nM (CQ-s), and 27.5 nM (CQ-r). In vivo antiplasmodial studies with P. falciparum infected mice showed an effect of 4,7-dichloroquinoline compared to chloroquine. The quinoline compound showed significant activity against the viral pathogen serotype 2 (DENV-2). In vitro conditions and the purified quinoline exhibited insignificant toxicity on the host system up to 100 µM/mL. Overall, 4,7-dichloroquinoline could provide a good anti-vectorial and anti-malarial agent.

D319 induced antifungal effects through ROS-mediated apoptosis and inhibited isocitrate lyase in Candida albicans

BackgroundCandida albicans (C. albicans) is an opportunistic pathogen that can cause superficial and life-threatening systemic infections in immunocompromised patients. However, the available clinically antifungals are limited. Therefore, the development of effective antifungal agents and therapies is urgently needed. Quinoline type of compounds were reported to possess potent anti-fungal effect. A series of quinoline derivatives were synthesized. Moreover their inhibitory activities and mechanisms on C. albicans were evaluated in this study. MethodsThe structure of D319 was identified by extensive spectroscopic analysis. The antifungal activity of D319 on C. albicans was evaluated using conventional methods, including the inhibition zone diameters with filter paper, Clinical Laboratory Standard Institute (CLSI) broth microdilution method in vitro, and in a murine model in vivo. Flow cytometry, fluorescence microscopy, western blot, knockout mutant and revertant strain techniques, and molecular modeling were applied to explore the mechanism of action of D319 in anti-Candida. ResultsD319 exhibited potent anti-Candida activity with Minimum Inhibitory Concentration value of 2.5 μg/mL in vitro. D319 significantly improved survival rate and reduced fungal burden compared to vehicle control in a murine model in vivo. The treatment of C. albicans with D319 resulted in fungal apoptosis through reactive oxygen species (ROS) accumulation in C. albicans. Furthermore, D319 inhibited the glyoxylate enzyme isocitrate lyase (ICL) of C. albicans, which was also confirmed by docking analysis. ConclusionsQuinoline compound D319 exhibited strong anti-Candida activities in vitro and in vivo models through inhibiting ICL activity and ROS accumulation in C. albicans. General significanceThis study showed that compound D319 as a novel isocitrate lyase inhibitor, would be a promising anti-Candida lead compound, which provided a potential application of this type of compounds in fighting clinical fungal infections. Furthermore, this study also supported ICL as a potential target for anti-Candida drug discovery.

Design, synthesis, and molecular dynamics simulation studies of quinoline derivatives as protease inhibitors against SARS-CoV-2

A new series of quinoline derivatives has been designed and synthesized as probable protease inhibitors (PIs) against severe acute respiratory syndrome coronavirus 2. In silico studies using DS v20.1.0.19295 software have shown that these compounds behaved as PIs while interacting at the allosteric site of target Mpro enzyme (6LU7). The designed compounds have shown promising docking results, which revealed that all compounds formed hydrogen bonds with His41, His164, Glu166, Tyr54, Asp187, and showed π-interaction with His41, the highly conserved amino acids in the target protein. Toxicity Prediction by Komputer Assisted Technology results confirmed that the compounds were found to be less toxic than the reference drug. Further, molecular dynamics simulations were performed on compound 5 and remdesivir with protease enzyme. Analysis of conformational stability, residue flexibility, compactness, hydrogen bonding, solvent accessible surface area (SASA), and binding free energy revealed comparable stability of protease:5 complex to the protease: remdesivir complex. The result of hydrogen bonding showed a large number of intermolecular hydrogen bonds formed between protein residues (Glu166 and Gln189) and ligand 5, indicating strong interaction, which validated the docking result. Further, compactness analysis, SASA and interactions like hydrogen-bonding demonstrated inhibitory properties of compound 5 similar to the existing reference drug. Thus, the designed compound 5 might act as a potential inhibitor against the protease enzyme. Communicated by Ramaswamy H. Sarma Highlights Quinoline derivatives have been designed as protease inhibitors against SARS-CoV-2. The compounds were docked at the allosteric site of SARS-CoV-2-Mpro enzyme (PDB ID: 6LU7) to study the stability of protein-ligand complex. Docking studies indicated the stable ligand-protein complexes for all designed compounds. The Toxicity Prediction by Komputer Assisted Technology protocol in DS v20.1.0.19295 software was used to evaluate the toxicity of the designed quinoline derivatives. Molecular dynamics studies indicated the formation of stable ligand-Mpro complexes.

Eco-Friendly Synthesis, Biological Evaluation, and In Silico Molecular Docking Approach of Some New Quinoline Derivatives as Potential Antioxidant and Antibacterial Agents.

A new series of quinoline derivatives 5–12 were efficiently synthesized via one-pot multicomponent reaction (MCR) of resorcinol, aromatic aldehydes, β-ketoesters, and aliphatic/aromatic amines under solvent-free conditions. All products were obtained in excellent yields, pure at low-cost processing, and short time. The structures of all compounds were characterized by means of spectral and elemental analyses. In addition, all the synthesized compounds 5–12 were in vitro screened for their antioxidant and antibacterial activity. Moreover, in silico molecular docking studies of the new quinoline derivatives with the target enzymes, human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, were achieved to endorse their binding affinities and to understand ligand–enzyme possible intermolecular interactions. Compound 9 displayed promising antioxidant and antibacterial activity, as well as it was found to have the highest negative binding energy of -9.1 and -9.3 kcal/mol for human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, respectively. Further, it complied with the Lipinski’s rule of five, Veber, and Ghose. Therefore, the quinoline analogue 9 could be promising chemical scaffold for the development of future drug candidates as antioxidant and antibacterial agents.

The discovery of quinoline derivatives, as NF-κB inducing kinase (NIK) inhibitors with anti-inflammatory effects in vitro, low toxicities against T cell growth

NIK is a critical regulatory protein of the non-classical NF-kB pathway, and its dysregulated activation has been proved to be one of the pathogenic factors in a variety of autoimmune diseases and inflammatory diseases. Nevertheless, its corresponding development of inhibitors faces many obstacles, including the lack of structure types of known inhibitors, immature activity evaluation methods of compounds in vitro. In this study, a series of quinoline derivatives were obtained through rational design and chemical synthesis. Among them, the representative compounds 17c and 24c have excellent inhibitory activities on LPS-induced macrophage (J774) nitric oxide release and anti-Con A-stimulated primary T cell proliferation. This evaluation method has good universality and overcomes the obstacles mentioned above, which are faced by the current inhibitor research to a certain extent. Besides, the compound's toxicity against the growth of T cells under non-stress conditions was evaluated, for the first time, as an indicator for the investigation to avoid potential safety risks. Pharmacokinetic properties evaluation of the less toxic compound 24c confirmed its good metabolic behavior (especially oral properties, F% = 21.7%), and subsequent development value.

Design, Synthesis, and Cytotoxic Screening of New Quinoline Derivatives over MCF-7 Breast Cancer Cell Line

VEGFR-2 inhibition represents an attractive strategy for anticancer drug design. A new series of quinoline derivatives were synthesized and structurally confirmed with different spectroscopic techniques. VEGFR-2 inhibition assay showed that 2-(4-bromoquinolin-3-yloxy)-1-(4-chlorophenyl)ethanone (V) demonstrated potent VEGFR-2 inhibitory activities. In addition, the brominated quinoline (V) exhibit antitumor activity over MCF-7 cell line via cell cycle arrest at G1 phase and apoptosis inducing activity as revealed by cell cycle analysis and Annexin V/FITC staining assays. Moreover, brominated quinoline (V) was proved to upregulate expression of proteins that trigger apoptosis such as increased Bax, decreased Bcl-2 as well as increased Bax/Bcl-2 ratio.

Mechanochemical Synthesis of Functionalized Quinolines by Iodine Mediated Oxidative Annulation

An iodine-mediated environmentally benign synthesis of multi-substituted quinoline derivatives is developed using a solvent-free mechanochemical process. Appropriately designed and easily accessible protecting group-free aniline derivatives were used for the oxidative annulation reaction, and a series of quinoline derivatives with variable functionalities were synthesized up to 89 % isolated yield. Importantly, the activator iodine remains in the quinoline molecule and promotes further functionalizations. The present methodology is beneficial with regard to operational simplicity and mild reaction conditions.

Design, Synthesis, and Antifungal Evaluation of Novel Quinoline Derivatives Inspired from Natural Quinine Alkaloids.

Inspired by quinine and its analogues, we designed, synthesized, and evaluated two series of quinoline small molecular compounds (a and 2a) and six series of quinoline derivatives (3a-f) for their antifungal activities. The results showed that compounds 3e and 3f series exhibited significant fungicidal activities. Significantly, compounds 3f-4 (EC50 = 0.41 μg/mL) and 3f-28 (EC50 = 0.55 μg/mL) displayed the superior in vitro fungicidal activity and the potent in vivo curative effect against Sclerotinia sclerotiorum. Preliminary mechanism studies showed that compounds 3f-4 and 3f-28 could cause changes in the cell membrane permeability, accumulation of reactive oxygen species, loss of mitochondrial membrane potential, and effective inhibition of germination and formation of S. sclerotiorum sclerotia. These results indicate that compounds 3f-4 and 3f-28 are novel potential fungicidal candidates against S. sclerotiorum derived from natural products.

Synthesis and Anti-Tumor Activity Evaluation of Novel 7-Fluoro-4-(1- Piperazinyl) Quinolines

Background: Three series of new 7-fluoro-4-(1-piperazinyl) quinolines (I1~I6, II1~II2 and IV1~IV4) were synthesized. Their anti-tumor activity was evaluated in vitro against three human carcinoma cell lines, namely SGC-7901 cells, BEL-7402 cells and A549 cells expressing high levels of EGFR by Methyl Thiazolyl Terazolium (MTT) assay. Methods: Three series of quinoline derivatives were synthesized, characterized and evaluated for their in vitro anti-tumor activities. Results and Discussion: Structures of the newly synthesized compounds were confirmed by spectral analysis. The preliminary bioassay indicated that compounds I1, I10 and II1 exhibited better anti-tumor activity than the rest of the target compounds and gefitinib against A549 cell based assay, which demonstrated that compounds I1, I10 and II1 are potential agents for cancer therapy. Results suggested that the substitutes on piperazinyl influenced anti-tumor activities remarkably. Conclusion: These results are useful for discovering more potent novel anti-tumor compounds and further studies are ongoing.

Synthesis and SAR development of quinoline analogs as novel P2X7 receptor antagonists.

The P2X7 receptor (P2X7R) plays an important role in diverse conditions associated with tissue damage and inflammation, suggesting that the human P2X7R (hP2X7R) is an attractive therapeutic target. In the present study, the synthesis and structure-activity relationship (SAR) of a novel series of quinoline derivatives as P2X7R antagonists are described herein. These compounds exhibited mechanistic activity (YO PRO) in an engineered HEK293 expressing hP2X7R as well as a functional response (IL-1β) in human THP-1 (hTHP-1) cellular assays. Compound 19 was identified as the most promising compound in this series with excellent cellular potency, low liver microsomal clearance, good permeability and low efflux ratio. In addition, this compound also displayed good pharmacokinetic properties and acceptable brain permeability (Kp,uu of 0.37).

Synthesis of novel amodiaquine analogs and evaluation of their in vitro and in vivo antimalarial activities.

Due to the rapid increase of drug resistance in Plasmodium parasites, there is a pressing need of developing new antiplasmodial drugs. In this study, new amodiaquine (AQ) analogs were synthesized, followed by an evaluation of their antiplasmodial activity. A new series of quinoline derivatives containing N-alkyl (piperazin-1-yl)methyl benzamidine moiety was synthesized by reacting 4-[(4-(7-chloroquinolin-4-yl)piperazin-1-yl)methyl]benzonitrile with appropriate primary amines. The synthesized compounds were investigated for inhibitory activity by inhibition test of heme detoxification (ITHD). Their antiplasmodial activity was then evaluated using the classical 4-day suppressive test (Peter's test) against Plasmodium berghei-infected mice (ANKA strain). The results showed that the percentage of heme detoxification inhibition in the active compounds was 90%. The most promising analogs, N-butyl-4-[(4-(7-chloroquinolin-4-yl)piperazin-1-yl)methyl]benzamidine (compound 1e), and 4-[(4-(7-chloroquinolin-4-yl)piperazin-1-yl)methyl)]-N-(4-methylpentan-2-yl)benzamidine (compound 1f) displayed 97.65 and 99.18% suppressions at the doses of 75 and 50 mg/kg/day, respectively. Further, the mean survival time of the mice treated with these compounds was higher than that of the negative control group. The newly synthesized amodiaquine analogs presented sufficient antiplasmodial activity with excellent suppressions and high in vitro heme detoxification inhibition. Higher mean survival time of the mice treated with synthetic compounds further confirmed the in vivo antimalarial activity of these new AQ analogs. Therefore, these compounds have the potential to replace common drugs from 4-aminoquinoline class. However, further investigations such as pharmacokinetic evaluations, cytotoxicity, toxicity, and formulation seem to be necessary.

Discovery and design of new PI3K inhibitors through pharmacophore-based virtual screening, molecular docking, and binding free energy analysis

Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/the mammalian target of rapamycin (mTOR) signaling pathway is one of the sought after therapeutic target for treating human cancers. This pathway is often hyper activated in cancers. In the present study, pharmacophore-based virtual screening, molecular docking, and binding free energy calculations were performed on a series of quinoline derivatives which were reported to be effective against PI3Kα. A five-point pharmacophore hypothesis with one hydrogen bond acceptor (A), one hydrogen bond donor (D), one hydrophobic group (H), and two aromatic rings (R) was developed with acceptable R2 and Q2 values of 0.93 and 0.60 respectively. Eventually, common pharmacophore hypothesis-based screening was conducted against TOSLab, CPP, and ASINEX macrocylce databases, and potential hits were identified which were further subjected to rigorous docking process in order to screen out drug like molecules having crucial interactions with the target PI3Kα. Finally, binding free energy analysis was carried out for the top hits obtained from docking process. We also designed new 1, 3, 4-oxadiazole-based cyclic peptides by incorporating the structural features of the hits obtained from the above databases. Among the designed cyclic peptides, the cyclic peptide with tryptophan moiety showed good interactions and free binding energy values. On the whole, this study helped us in identifying new promising molecules as PI3Kα inhibitors which can be explored further to generate greater number of compounds with better pharmacokinetic properties.

Comprehensive exploration of the optical and biological properties of new quinoline based cellular probes

A series of quinoline derivatives containing bithiophene and N-octyl-carbazole moieties and a variety of substituents in the quinoline core were synthesized and characterized. The influence of bithienyl and N-octyl-carbazyl substituents on the photophysical properties of novel quinolines were thoroughly investigated and supported by DFT calculations. The absorption and emission maxima of quinolines are located at 373-412 and 410–606 nm, respectively, which considerably red-shifts when an electron-withdrawing substituent (NO2) is introduced to the quinoline ring. The quantum yield and lifetime for carbazyl-substituted quinolines are considerably higher (Φem = 9–70%, τ = 0.83–5.72 ns) compared to their bithiophene substituted counterparts (Φem = 18–53%, τ = 0.61–1.46 ns) resulting from greater planarity of carbazyl-substituted quinolines as proved by theoretical calculations. The carbazyl functional group in quinolines has immense impact on values of Δμ (13.83–15.50 D) indicating that the electron-donating ability of carbazole moiety relative to bithiophene motif (Δμ = 9.16–13.83) in studied quinolines is more predisposed to intramolecular charge transfer (ICT). The capability of the novel compounds for cellular staining was investigated. All examined quinoline derivatives penetrate cell organelles quickly and efficiently with good overall fluorescence and signal to noise ratio. Relative lack of toxicity make them useful in such applications.

Zirconium-mediated selective synthesis of quinoline derivatives

A series of quinoline derivatives was obtained in high yields by an efficient one-pot reaction of substituted o-diiodobenzenes with azazirconacyclopentadienes, which were conveniently prepared from one internal alkyne and one nitrile mediated by zirconocene. This proposed synthetic method provides a feasible way to the synthesis of large N-heterocyclic π-conjugated molecules.

Synthesis and biological evaluation of quinoline derivatives as potential anti-prostate cancer agents and Pim-1 kinase inhibitors

In this work, a series of quinoline derivatives were designed and synthesized as antitumor agents. Most quinolines showed potent anti-proliferative activity against human prostatic cancer PC-3 cell line. Among which, 9d, 9f and 9g were the most effective compounds with GI50 values of 2.60, 2.81 and 1.29μM, respectively. Structure–activity relationship analysis indicated that the secondary amine linked quinoline and pyridine ring played an important role in the anti-proliferative effects. Mechanistic studies revealed that 9g was a potential Pim-1 kinase inhibitor with abilities of cell cycle arrest and apoptosis induction. Considering of the increased activity of Pim-1 in prostate cancer, such compounds have potential to be developed as anti-prostate cancer agents.