Good Antiproliferative Activity Research Articles

Design, synthesis, stereochemical determination, molecular docking study, in silico pre-ADMET prediction and anti-proliferative activities of indole-pyrimidine derivatives as Mcl-1 inhibitors

In this study, fourteen novel indole-pyrimidine hybrids were designed and synthesized. Their chemical structures were confirmed using different spectroscopic techniques (1H NMR, 13C NMR, IR and mass). Their (E) stereochemical configuration was determined theoretically (MM2 property) and experimentally using 2D NMR technique (NOESY experiment). The prepared compounds were subjected to preliminary biological studies as Mcl-1 inhibitors. Most of the compounds exhibited good abilities for targeting Mcl-1 protein, especially, 7d, 7e, 7i and 7k (Ki = 11.19–15.21 nM). These derivatives were further evaluated against Bcl-XL and Bcl-2 proteins. Some compounds were found to have dual Mcl-1/Bcl-XL such as 7i, or Bcl-XL/Bcl-2 inhibitory activity as 7d.The most potent derivatives as Mcl-1 inhibitors were chosen as representative examples for determination of in-vitro anti-proliferative activity against PC-3, K-562 and MDA-MB-231 cell lines. They possessed excellent to good anti-proliferative activities. All of the synthesized compounds were docked into Mcl-1 active site. Drug-likeness properties and in silico pre-ADMET characters were also predicted.

Anticancer and Structure Activity Relationship of Non-Symmetrical Choline Kinase Inhibitors.

Choline kinase inhibitors are an outstanding class of cytotoxic compounds useful for the treatment of different forms of cancer since aberrant choline metabolism is a feature of neoplastic cells. Here, we present the most in-depth structure-activity relationship studies of an interesting series of non-symmetric choline kinase inhibitors previously reported by our group: 3a–h and 4a–h. They are characterized by cationic heads of 3-aminophenol bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium through several linkers. These derivatives were evaluated both for their inhibitory activity on the enzyme and their antiproliferative activity in a panel of six human tumor cell lines. The compounds with the N-atom connected to the linker (4a–h) show the best inhibitory results, in the manner of results supported by docking studies. On the contrary, the best antiproliferative compounds were those with the O-atom bounded to the linker (3a–h). On the other hand, as was predictable in both families, the inhibitory effect on the enzyme is better the shorter the length of the linker. However, in tumor cells, lipophilicity and choline uptake inhibition could play a decisive role. Interestingly, compounds 3c and 4f, selected for both their ability to inhibit the enzyme and good antiproliferative activity, are endowed with low toxicity in non-tumoral cells (e.g., human peripheral lymphocytes) concerning cancer cells. These compounds were also able to induce apoptosis in Jurkat leukemic cells without causing significant variations of the cell cycle. It is worth mentioning that these derivatives, besides their inhibitory effect on choline kinase, displayed a modest ability to inhibit choline uptake thus suggesting that this mechanism may also contribute to the observed cytotoxicity.

Anticancer activity of gold nanobioconjugates synthesized from Elephantopus scaber (linn.) leaf extract.

Medicinal plants are the major natural resources for the treatment of human ailments including cancer therapy. The current cancer treatments such as surgery, radiation, and chemotherapy affect normal cells too. Thus, treatments like synthesized nanoscale particles using plant extracts have proven to be potential anticancer agent. We hypothesize that the gold nanoparticles (AuNPs) synthesized using Elephantopus scaber hydro-methanolic extract may have anti-cancer activity along with their synergistic counterparts with adriamycin (ADR) on human breast cancer MCF-7: human breast cancer (A-549), human oral cancer (squamous cell carcinoma [SCC]-40), and COLO-205: human colon cancer cell lines. The phytosynthesized AuNPs were characterized for ultraviolet-visible (UV-Vis) spectroscopy, nanoparticle tracking analysis (NTA), X-ray diffraction, scanning electron microscopy, transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) analysis. The anticancer ability of the AuNPs against human MCF-7, A-549, SCC-40, and COLO-205 through sulforhodamine B assay has been studied. The synthesis of AuNPs was confirmed with the UV-Vis spectrophotometer with a peak at 540 nm. The FTIR analysis showed polyphenolic groups were major found to be the reduction and capping agent for AuNPs. According to the results obtained, AuNPs showed good anti-proliferative activity with GI50 <10 μg/ml on MCF-7 cancer cell line. The synergistic effect of AuNPs + ADR was even better for all the four cell lines than that of the AuNPs alone. The green synthesis of AuNPs is a simple, eco-friendly, and cost-effective method with dominantly spherical morphology ranging from 20 to 40 nm confirmed by NTA and TEM analysis. The study reveals the potent therapeutic value of the AuNPs.

Carboxamide appended quinoline moieties as potential anti-proliferative agents, apoptotic inducers and Pim-1 kinase inhibitors

The targeted approach of protein kinases (PKs), as PKs are the main regulators of cell survival and proliferation, has been a promising strategy for cancer treatments. Here we analyse the potential of quinoline-carboxamide derivatives for four cell lines: MCF-7, CACO, HepG-2 and HCT-116 as anticancer agents. 3e, 4b, 11b and 13d derivatives showed good anti-proliferative activities in comparison to the reference standard Doxorubicin, against the four cell lines tested. They have been chosen for further studies. First of all, the IC50 value surveys were carried out to ensure the protection of our hits and demonstrate that the cytotoxic effect (IC50 > 113 μM) is highly selective on normal human cells (WI-38). Secondly, apoptosis was accomplished by down-regulation of Bcl-2 and up-regulation of BAX and Caspase-3 by these active compounds. Also, the Pim-1 inhibitory activity of the active hybrids was done, which indicates that compound 3e was the most active with the percentage of inhibition 82.27% and IC50 equals 0.11 when compared to SGI-1776 as a reference standard. In addition, by in silico assessment of ADME properties, all of the strongest compounds are orally bioavailable without blood–brain barrier penetration.

Green synthesis of glyco-phenol by enzymatic coupling between ferulic acid and glucosamine: An ecofriendly procedure.

A new glyco-phenol was produced by the coupling between glucosamine (Glu) and ferulic acid (FA) using Myceliophthora thermophila laccase as biocatalyst in mild conditions (distilled water and 30°C) as an environmentally friendly process. Results indicated that the enzymatic reaction created a new derivative (FA-Glu), produced from coupling between Glu and FA by covalent bonds. By the high production of (FA-Glu) derivative and its stability, the optimal ratio of (FA:Glu) was of (1:1) at optimal time reaction of 6h. Under these optimal conditions, almost 55% of -NH2 groups on Glu were bound with FA oxidation products. The new derivative showed higher hydrophobic character than Glu due to the presence of FA in its structure. Liquid chromatography-mass spectrometry analysis showed that (FA-Glu) derivative exhibited a molecular mass at MM 713g/mol containing one Glu molecule and three FA molecules after decarboxylation. Furthermore, the new derivative presented good antioxidant and antiproliferative activities in comparison with Glu and FA. These results suggest that the enzymatic conjugation between Glu and FA is a promising process to produce a new glyco-phenol having good functional properties for potential applications.

Anti-tumor compounds identification from gossypol Groebke imidazopyridine product

Series of imidazo[1,2-a]pyridines designed from gossypol modification based on Groebke-Blackburn-Bienaymé reaction were discovered as potent Bcl-2 inhibitors. Compound 4 was found to display good anti-proliferative activities for 7 human cancer cell lines (0.33–1.7 µM) among them, which were better than separate gossypol and imidazopyridine moiety compounds. It was capable of suppressing antiapoptotic proteins Bcl-2 and Bcl-XL demonstrated by mechanism studies, and possible binding model was also illustrated by molecular modelling.

High activity, high selectivity and high biocompatibility BODIPY-pyrimidine derivatives for fluorescence target recognition and evaluation of inhibitory activity

BODIPY-Pyrimidine (BP) is a highly selective, highly active, and highly biocompatible fluorescent drug, which is characterized by its own activity combined with a fluorophore. The combination of pyrimidines with good biological activity and fluorophores to obtain new compounds with both anti-tumor activity and fluorescent targeting probe functions is the focus of this research. In terms of biological activity, in vitro cytotoxicity of the compounds on four human cancer cells (HepG2, HeLa, A-459, and HCT-116) and the human normal cell line L-02 was studied. BP-4 has good antiproliferative activity, and its IC50 values are 19.12 ± 2.29, 13.47 ± 3.80, 18.59 ± 7.42, 14.57 ± 2.44 and 92.48 ± 6.03 μM, respectively. Good biocompatibility with tumor cells can be observed in cell imaging. The anti-tumor mechanism of the compound was further studied by flow cytometry. After BP-2, BP-3 and BP-4 treated HeLa cells, the percentage of apoptotic cells was 19.07%, 22.09% and 27.3%, respectively. The cell cycle study found that, compared with the positive control 5-FU (48.05%), the compounds BP-2, BP-3 and BP-4 all increased the proportion of HeLa cells in the G1 phase, reaching 57.65%, 55.46% and 53.58%, respectively. In vivo bioimaging results show that all three compounds can be targeted and accurately expressed in tumor tissues. In addition, molecular docking analyzes the possible interaction between the compound and the active site of thymidylate synthase.

2D-Quantitative structure activity relationship (QSAR) modeling, docking studies, synthesis and in-vitro evaluation of 1,3,4-thiadiazole tethered coumarin derivatives as antiproliferative agents

Cancer is one of the leading causes of deaths globally. Despite many anticancer agents in the market, cancer stood as a major health concern to humanity due to the problems like drug resistance, toxicities and economic burden etc., and these issues strongly impose the scientists for the development of novel anticancer agents. Hence, in the current investigation, we performed the 2D-QSAR (Quantitative Structure-Activity Relationship) analysis of a series of compounds reported with a potential antiproliferative activity using multiple regression analysis and designed compounds from the obtained QSAR model. The generated Multiple Linear Regression (MLR) equations were validated both internally and externally. The applicability domain has been done for the developed model. Based on the generated QSAR equations, a series of 2-amino-5-substituted-1,3,4-thiadiazole derivatives were designed and their antiproliferative activity was predicted using the QSAR equations. Further, molecular docking studies were carried out for the designed compounds using Autodock 4 against Epidermal Growth Factor Receptor (EGFR) kinase. The compounds with good binding affinity were synthesized and characterized by FT-IR, NMR and mass spectroscopy and evaluated for their antiproliferative activity against MCF-7 and PC3 cell lines considering the overexpression of EGFR kinase in breast and prostate cancers. The generated best model exhibited an r2 value of 0.93, q2LOO = 0.92, r2cv = 0.78. From the results, compound 3b and 3c exhibited good antiproliferative activity. The results of the study suggest that the synthesized active compound could serve as a lead for generating good biological agents against EGFR kinase.

Design, synthesis, and biological evaluation of 3-(1-benzotriazole)-nor-β-lapachones as NQO1-directed antitumor agents

A series of novel 3-(1-benzotriazole)-nor-β-lapachones 5a–5l were synthesized as the NQO1-targeted anticancer agents. Most of these compounds displayed good antiproliferative activity against the breast cancer MCF-7, lung cancer A549 and hepatocellular carcinoma HepG2 cells in agreements with their NQO1 activity. Among them, compound 5k was identified as a favorable NQO1 substrate. It could activate the ROS production in a NQO1-dependent manner, arrest tumor cell cycle at G0/G1 phase, promote tumor cell apoptosis, and decrease the mitochondrial membrane potential. In HepG2 xenograft models, 5k significantly suppressed the tumor growth with no influences on animal body weights. Therefore, 5k could be a good lead for further anticancer drug developments.

In vitro and in silico growth inhibitory, anti-ovarian & anti-lung carcinoma effects of 1,5 diarylpenta-1,4-dien-3-one as synthetically modified curcumin analogue

The synthesized 1,5 diarylpenta-1,4-dien-3-one derivatives (compounds 1-6) as synthetic curcumin analogues were tested for their potential anticancer activity against human ovarian and lung adenocarcinoma cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET/pharmacokinetic) parameters of all the compounds were predicted by admetSAR software. The pharmacokinetics, pharmacodynamics and bioactivity scores properties based on Lipinski rule and Ghose filter, calculated with the help of Molinspiration and ChemDraw. Molecular docking evaluation of all the compounds was also performed by using AutoDock Vina and iGEMDOCK against three most common human anticancer targets; epidermal growth factor receptor (EGFR), heat shock protein (Hsp 90-α), and vascular endothelial growth factor receptor-2 (VEGFR2). The obtained results were compared with the reference compound 7 and drugs 8-10 (7: GO-035; 8: Quinazolin; 9: Naquotinib and 10: Ribofuranuronamide). Finding indicates, all the compounds were potentially interacting with VEGFR2 through the average –9.1 binding energy (BE) with closer contact <5.0 Å deep in the active site of the ligand-receptor complex. All the compounds showed excellent oral bioavailability, bioactivity score, and none of the compounds are virtually found to be toxic. Compounds 1-6 were also successfully characterized by the physical properties as well as spectroscopic techniques (FT-IR and 1H-NMR). In vitro anti-proliferative activity was tested via MTT method against human ovarian carcinoma (PA-1) and human lung adenocarcinoma (A549) cells and further screened for apoptotic parameters such as nuclear fragmentation and ROS generation. Compound 4 exhibits good dose-dependent anti-proliferative activity (IC50 73 and 79.7 µM) against human ovarian carcinoma and human lung adenocarcinoma, respectively. Communicated by Ramaswamy H. Sarma

New Hybrids Based on Curcumin and Resveratrol: Synthesis, Cytotoxicity and Antiproliferative Activity against Colorectal Cancer Cells.

We synthesized twelve hybrids based on curcumin and resveratrol, and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated against SW480 human colon adenocarcinoma cells, its metastatic derivative SW620, along with the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 3e and 3i (for SW480) and 3a, 3e and 3k (for SW620) displayed the best cytotoxic activity with IC50 values ranging from 11.52 ± 2.78 to 29.33 ± 4.73 µM for both cell lines, with selectivity indices (SI) higher than 1, after 48 h of treatment. Selectivity indices were even higher than those reported for the reference drug, 5-fluorouracil (SI = 0.96), the starting compound resveratrol (SI = 0.45) and the equimolar mixture of curcumin plus resveratrol (SI = 0.77). The previous hybrids showed good antiproliferative activity.

Synthesis of 5H‐indeno[1,2‐b]pyridine derivatives: Antiproliferative and antimetastatic activities against two human prostate cancer cell lines

This study describes the direct synthesis of 2-amino-4-(phenylsubstituted)-5H-indeno[1,2-b]pyridine-3-carbonitrile derivatives 5-21, through sequential multicomponent reaction of aromatic aldehydes, malononitrile, and 1-indanone in the presence of ammonium acetate and acetic acid (catalytic). The biological study showed that compound 10 significantly impeded proliferation of the cell lines PC-3, LNCaP, and MatLyLu. The antimetastatic effects of compound 10 could be related with inhibition of MMP9 in the PC-3 and LNCaP human cell lines. On the basis of a study of the structure-activity relationship of these compounds, we propose that the presence of two methoxy groups at positions 6 and 7 of the indeno nucleus and a 4-hydroxy-3-methoxy phenyl substitution pattern at position 4 of the pyridine ring is decisive for these types of molecules to exertvery good antiproliferative and antimetastatic activities.

Discovery of novel tetrahydrobenzo[b]thiophene-3-carbonitriles as histone deacetylase inhibitors

The discovery and development of isoform-selective histone deacetylase (HDAC) inhibitor is a challenging task because of the sequence homology among HDAC enzymes. In the present work, novel tetrahydro benzo[b]thiophene-3-carbonitrile based benzamides were designed, synthesized, and evaluated as HDAC inhibitors. Pharmacophore modeling was our main design strategy, and two novel series of tetrahydro benzo[b]thiophene-3-carbonitrile derivatives with piperidine linker (series 1) and piperazine linker (series 2) were identified as HDAC inhibitors. Among all the synthesised compounds, 9h with 4-(aminomethyl) piperidine linker and 14n with piperazine linker demonstrated good activity against human HDAC1 and HDAC6, respectively. Both the compounds also exhibited good antiproliferative activity against several human cancer cell lines. Both these compounds (9h and 14n) also induced cell cycle arrest and apoptosis in U937 and MDA-MB-231 cancer cells. Overall, for the first time, this research discovered potent isoform-selective HDAC inhibitors using cyclic linker instead of the aliphatic chain and aromatic ring system, which were reported in known HDAC inhibitors.

Synthesis and in vitro study of antiproliferative benzyloxy dihydropyrimidinones.

In this study, we report on antiproliferative benzyloxy dihydropyrimidinones (DHPMs) produced by the Biginelli reaction of benzyloxy benzaldehyde, urea, and diverse 1,3-diones. The reaction was catalyzed by lanthanum triflate and completed within 1-1.5 h, with 74-97% yield. The antiproliferative assay was carried out for all synthesized dihydropyrimidinones against six human solid tumor cell lines. Six compounds showed good antiproliferative activity with GI50 values below 5 μM. Among all the synthesized compounds, the most potent derivative showed good antiproliferative activity against all cell lines with GI50 values in the range of 1.1-3.1 μM. These DHPMs comply with druglikeness. Furthermore, ADMET prediction and the effect of P-glycoprotein on the antiproliferative activity were also studied. Overall, our method allows eco-friendly access to benzyloxy DHPMs as potential anticancer drugs.

Antiproliferative, Apoptotic Effects and Suppression of Oxidative Stress of Quercetin against Induced Toxicity in Lung Cancer Cells of Rats: In vitro and In vivo Study

In the present study, quercetin was examined against lung human cancer cells using A549 and H69 cancer cell lines in addition to normal non cancer cells (W138). Two genes Bax and Bcl-2 that play an important role in apoptosis pathways were investigated. Also Immunohistochemical study for caspase-3 which is considered as indicator for apoptosis was performed. Quercetin showed good anti proliferative activity against tested lung cancer cell lines, IC50 values on A549 are 8.65, 7.96 and 5.14 µg/ml at 24, 48 and 72h respectively. Also significant effects of quercetin on Bax, Bcl-2 and caspase-3 were observed, that can prove its ability to induce apoptosis. On the other hand quercetin showed good therapeutic effects against cyclophosphamide induced lung toxicity that were observed in the histopathology study. In vitro studies were also performed such as cell cycle analysis through flowcytometry. The obtained results from all these performed analysis proved that quercetin can induce apoptosis in human lung cancer cells, additionally quercetin showed ability to reduce MDA and increase SOD and GSHP levels which indicates its ability in suppressing oxidative stress, Quercetin has played a therapeutic role in cyclophosphamide induced lung toxicity as it has improved restoring of the damaged lung tissue as discussed in this research work.

Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer

In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates (5a–e and 7a–i) was designed and synthesised. The anticancer activity for compounds (5b–d, 7a, 7b, 7d and 7g) was measured against NCI-55 human cancer cell lines. Compound 5d was the most efficient, and thus subjected to the five-dose screen where it showed excellent broad activity against almost all tested cancer subpanels. Furthermore, all conjugates (5a–e and 7a–i) showed a good anti-proliferative activity towards colorectal cancer SW-620 and HT-29 cell lines, with an excellent inhibitory effect for compounds 5a and 5d (IC50 = 8.7 and 9.4 µM (5a), and 6.5 and 9.8 µM for (5d), respectively). Both compounds displayed selective cytotoxicity with good safety profile. In addition, both compounds provoked apoptosis in a dose dependent manner in SW-620 cells. Also, they significantly inhibited the anti-apoptotic Bcl2 protein expression and increased the cleaved PARP level that resulted in SW-620 cells apoptosis.

Anticancer potential of 3-hydroxypyridine-2-carboxaldehyde N(4)-methyl and pyrrolidinylthiosemicarbazones and their Zn(II) complexes in different cancers via targeting MAPK superfamily signaling pathway

Zinc(II) complexes of 3-hydroxy-2-formylpyridine N(4)-methylthiosemicarbazone (1) and 3-hydroxy-2-formylpyridine N(4)-pyrrolidinyl thiosemicarbazone (2) respectively have been synthesized and characterized by elemental analysis, IR, UV–Vis, 1H NMR spectroscopy and mass spectrometry. These compounds were investigated for their antiproliferative potential against PC3 (Prostate Cancer), DU145 (Prostate Cancer), A549 (Lung Cancer), A431 (skin cancer) and Hela (Cervical Cancer cell) cell lines. All the compounds showed good antiproliferative activity against the tested cell lines. However, compound HHyPyPyrd showed remarkable antiproliferative activity against PC3 cell line with an IC50 of 0.69 µM. Cell death analysis by propidium iodide staining showed significant increase in cell death of PC3 cells in a concentration dependent manner. Furthermore, cell cycle analysis showed cell cycle arrest of PC3 cells at S phase. Our study shows that compound HHyPyPyrd induces the downregulation of JNK, c-Jun and Erk.

A new phenyl alkyl ester and a new combretin triterpene derivative from Combretum fragrans F. Hoffm (Combretaceae) and antiproliferative activity

AbstractThis work concerns the isolation and structure elucidation of compounds obtained from the extract of leaves and stem bark of Combretum fragrans F. Hoffm. Both extracts and some isolated compounds were tested for antiproliferative activity on glioblastoma (U87MG and C6 cells) and prostate (PC-3 cells) cancer cell lines using XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay. The dichloromethane/methanol (1:1) extract of the leaves led to the isolation of two new compounds such as fragransinate (1) and combretin C (2), alongside five known compounds such as combretin A (3), belamcanidin (4), cirsilineol (5), velutin (6), and a mixture of β-sitosterol-3-O-β-d-glucopyranoside (10a) and stigmasterol-3-O-β-d-glucopyranoside (10b), whereas the methanol extract of the stem bark led to the isolation of three known compounds betulinic acid (7), bellericagenin B (8), and a mixture of β-sitosterol (9a) and stigmasterol (9b). The structure of compounds was elucidated by nuclear magnetic resonance and mass spectrometry data. The methanol extract of the stem bark showed a powerful antiproliferative activity on all tested cells, as well as the extract of leaves which also showed important cytotoxicity effect. Compound (3) showed good antiproliferative activity particularly on U87MG and PC-3 cells, whereas compound (5) exhibits moderated activity. Compounds (2) and (8) were not active on all tested cells.

Discovery of new thieno[2,3-d]pyrimidine and thiazolo[5,4-d]pyrimidine derivatives as orally active phosphoinositide 3-kinase inhibitors

As abnormal PI3K signaling is a feature of many types of cancer, the development of orally active PI3K inhibitors is of great significance for targeted cancer therapy. Through integrating strategies of reducing aromatic character/increasing the fraction of sp3 carbons together with scaffold hopping, we designed and synthesized two new series of thieno[2,3-d]pyrimidine and thiazolo[5,4-d]pyrimidine derivatives for use as PI3K inhibitors. Our structure–activity relationship studies led to the identification of thieno[2,3-d]pyrimidine 6a and thiazolo[5,4-d]pyrimidine 7a, which exhibited remarkable nanomolar PI3K potency, good antiproliferative activity, favorable pharmacokinetic properties and significant in vivo anti-cancer efficacy. Notably, thiazolo[5,4-d]pyrimidine 7a had better anti-cancer activity than thieno[2,3-d]pyrimidine 6a and is worthy of further pre-clinical evaluation for its use in cancer treatment.

Identification of a potent and selective phosphatidylinositol 3-kinase δ inhibitor for the treatment of non-Hodgkin's lymphoma

PI3Kδ has proved to be an effective target for anti-lymphoma drugs. However, the application of current approved PI3Kδ inhibitors has been greatly limited due to their specific immune-mediated toxicity and increased risk of infection, it is necessary to develop more PI3Kδ inhibitors with new scaffold. In this study, SAR study with respect to piperazinone-containing purine derivatives led to the discovery of a potent and selective PI3Kδ inhibitor, 4-(cyclobutanecarbonyl)-1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperazin-2-one (WNY1613). WNY1613 exhibits good antiproliferative activity against a panel of non-Hodgkin's lymphoma (NHL) cell lines by inducing cancer cell apoptosis and inhibiting the phosphorylation of PI3K and MAPK downstream components. In addition, it can also prevent the tumor growth in both SU-DHL-6 and JEKO-1 xenograft models without observable toxicity. WNY1613 thus could be developed as a promising candidate for the treatment of NHL after subsequent extensive pharmacodynamics and pharmacokinetics investigation.