Cancer Drug Discovery Research Articles

Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro.

Current 3D cancer models (in vitro) fail to reproduce complex cancer cell extracellular matrices (ECMs) and the interrelationships occurring (in vivo) in the tumor microenvironment (TME). Herein, we propose 3D in vitro colorectal cancer microtissues (3D CRC μTs), which reproduce the TME more faithfully in vitro. Normal human fibroblasts were seeded onto porous biodegradable gelatin microbeads (GPMs) and were continuously induced to synthesize and assemble their own ECMs (3D Stroma μTs) in a spinner flask bioreactor. Then, human colon cancer cells were dynamically seeded onto the 3D Stroma μTs to achieve the 3D CRC μTs. Morphological characterization of the 3D CRC μTs was performed to assess the presence of different complex macromolecular components that feature in vivo in the ECM. The results showed the 3D CRC μTs recapitulated the TME in terms of ECM remodeling, cell growth, and the activation of normal fibroblasts toward an activated phenotype. Then, the microtissues were assessed as a drug screening platform by evaluating the effect of 5-Fluorouracil (5-FU), curcumin-loaded nanoemulsions (CT-NE-Curc), and the combination of the two. When taken together, the results showed that our microtissues are promising in that they can help clarify complex cancer-ECM interactions and evaluate the efficacy of therapies. Moreover, they may be combined with tissue-on-chip technologies aimed at addressing further studies in cancer progression and drug discovery.

Virtual Screening for Identification of Dual Inhibitors against CDK4/6 and Aromatase Enzyme.

CDK4/6 and aromatase are prominent targets for breast cancer drug discovery and are involved in abnormal cell proliferation and growth. Although aromatase inhibitors have proven to be effective (for example exemestane, anastrozole, letrozole), resistance to treatment eventually occurs through the activation of alternative signaling pathways, thus evading the antiproliferative effects of aromatase inhibitors. One of the evasion pathways is Cylin D-CDK4/6-Rb signaling that promotes tumor proliferation and resistance to aromatase inhibitors. There is significant evidence that the sequential inhibition of both proteins provides therapeutic benefits over the inhibition of one target. The basis of this study objective is the identification of molecules that are likely to inhibit both CDK4/6 and aromatase by computational chemistry techniques, which need further biochemical studies to confirm. Initially, a structure-based pharmacophore model was constructed for each target to screen the sc-PDB database. Consequently, pharmacophore screening and molecular docking were performed to evaluate the potential lead candidates that effectively mapped both of the target pharmacophore models. Considering abemaciclib (CDK4/6 inhibitor) and exemestane (aromatase inhibitor) as reference drugs, four potential virtual hit candidates (1, 2, 3, and 4) were selected based on their fit values and binding interaction after screening a sc-PDB database. Further, molecular dynamics simulation studies solidify the stability of the lead candidate complexes. In addition, ADMET and DFT calculations bolster the lead candidates. Hence, these combined computational approaches will provide a better therapeutic potential for developing CDK4/6-aromatase dual inhibitors for HR+ breast cancer therapy.

Investigation of novel ligand targeting bromodomain-containing protein 4 (BRD4) for cancer drug discovery: complete pharmacophore approach

The Bromodomain (BRD4) and extra-terminal (BET) protein family are reversible; lysine-acetylated epigenetic readers identified as key important epigenetic regulators for protein recognition in posttranslational modifications for targeting cancer for its role in super-enhancers and transcription of oncogene expression in cancer and other forms of cancer and various diseases. Firstly, JQ-1a small potent BET inhibitors, targeting BET proteins were currently in clinical trials to ablate cancer. The identified compounds were taken from the library of preexisting therapeutically potent molecules. The objective of the present study is to identify the potential small molecule inhibitors against BRD4 through in-silico approach for the treatment of cancer. In present study, designed an in-silico screening of small molecules through ligand-based pharmacophore studies against bromodomain-containing protein 4 (BRD-4) protein and used for virtual screening through Database and their binding affinity and interaction of identified molecules were predicted through molecular docking, molecular dynamics simulations for 12 fixed time period, Molecular mechanics (MMGBSA) binding free energy calculations, ADME with drug-likeness properties including violations of lipinski's rule of 5, Jorgensens rule of 3 and other parameters were studied. The docking results indicate from the reported database screened molecules were validated with docking score −7.92 to −4.27Kcal/mol for BRD4-BD1 and the best model identified 21 hits. Among these two drugs were filtered and scrutinized for their ability based on binding modes and common interaction, MMGBSA of the highest affinity −54.53 Kcal/mol of BRD4-BD1 and ADME properties of selected molecules were predicted for its various parameters, dynamics studies evaluating its binding stability using Maestro software. In Conclusion, two BRD4 inhibitors were found to bind strongly in the similar binding sites as JQ-1, highlighting the role of BRD4-BD1. These compounds were identified as promising new options for regulating epigenetics and understanding the structural needs of BRD4 protein, further research in these areas could lead to the development of more effective and targeted cancer drugs.Communicated by Ramaswamy H. Sarma

Phenotypic screening platform identifies statins as enhancers of immune cell-induced cancer cell death

BackgroundHigh-throughput screening (HTS) of small molecule drug libraries has greatly facilitated the discovery of new cancer drugs. However, most phenotypic screening platforms used in the field of oncology are based solely on cancer cell populations and do not allow for the identification of immunomodulatory agents.MethodsWe developed a phenotypic screening platform based on a miniaturized co-culture system with human colorectal cancer- and immune cells, providing a model that recapitulates part of the tumor immune microenvironment (TIME) complexity while simultaneously being compatible with a simple image-based readout. Using this platform, we screened 1,280 small molecule drugs, all approved by the Food and Drug Administration (FDA), and identified statins as enhancers of immune cell-induced cancer cell death.ResultsThe lipophilic statin pitavastatin had the most potent anti-cancer effect. Further analysis demonstrated that pitavastatin treatment induced a pro-inflammatory cytokine profile as well as an overall pro-inflammatory gene expression profile in our tumor-immune model.ConclusionOur study provides an in vitro phenotypic screening approach for the identification of immunomodulatory agents and thus addresses a critical gap in the field of immuno-oncology. Our pilot screen identified statins, a drug family gaining increasing interest as repurposing candidates for cancer treatment, as enhancers of immune cell-induced cancer cell death. We speculate that the clinical benefits described for cancer patients receiving statins are not simply caused by a direct effect on the cancer cells but rather are dependent on the combined effect exerted on both cancer and immune cells.

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia

Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions. With a renovated interest in natural remedies as a commodity and their essential role in cancer drug discovery, Malaysia is looking towards capitalizing on its mega biodiversity, which includes the oldest rainforest in the world and an estimated 1200 medicinal plants. We here explore whether the list of top Malay plants prioritized by the Malaysian government may fulfill the potential of becoming newer, sustainable sources of prostate cancer chemotherapy. These include Andrographis paniculate, Centella asiatica, Clinacanthus nutans, Eurycoma longifolia, Ficus deltoidea, Hibiscus sabdariffa, Marantodes pumilum (syn. Labisia pumila), Morinda citrifolia, Orthosiphon aristatus, and Phyllanthus niruri. Our review highlights the importance of resistance factors such as Smac/DIABLO in cancer progression, the role of the CXCL12/CXCR4 axis in cancer metastasis, and the regulation of PCa cells by some promising terpenes (andrographolide, Asiatic acid, rosmarinic acid), flavonoids (isovitexin, gossypin, sinensetin), and alkylresorcinols (labisiaquinones) among others.

Turning down PI3K/AKT/mTOR signalling pathway by natural products: an in silico multi-target approach

ABSTRACT The PI3K/AKT/mTOR pathway is a significant target for cancer drug discovery. Many efforts have focused on discovering new inhibitors against key kinase proteins involved in this pathway for cancer treatment. PI3K/mTOR dual inhibitors, such as PKI-179, have been reported to be more effective than agents that act only on a single protein target. The present computational study aimed to discover triple target inhibitors against PI3K, AKT, and mTOR proteins. Accordingly, the PI3K protein bound with the ligand was used as input for e-pharmacophore modelling to generate the pharmacophore hypothesis and then screened for a library of 270,540 natural products from the Zinc database resulting in 57,220 compounds that matched the hypothesis. These compounds were then docked into the active site of PI3K, resulting in 292 compounds with better docking scores than the co-crystallized ligand. These compounds were re-docked into AKT and mTOR proteins. Besides, MM-GBSA binding free energy calculations, MD simulations, and ADMET prediction were carried out, leading to 5 potential triple-target inhibitors namely, ZINC000014644152, ZINC000014760695, ZINC000014644839, ZINC000095099451, and ZINC000005998557. In conclusion, these inhibitors may be possible leads for inhibiting PI3K/AKT/mTOR pathway, and they may be further evaluated in vitro and clinically as anticancer agents.

Determining the roles of membrane tension in breast cancer cell migration

Within the past two years, breast cancer has exceeded lung cancer as the most frequently diagnosed cancer, ranking first for incidence and mortality in most of the world. Cancer reaches its deadliest stage when metastatic spread of cells occurs from tumor sites. Cell metastasis relies, in part, on 1) endocytic membrane trafficking and 2) the formation of adhesive contacts with the extracellular matrix. These processes are regulated by mechanical tension on the cell membrane, which varies spatially within migrating cells. While tension gradients assist in maintaining polarity of the cell during migration, recently it has been shown that these gradients create an asymmetry in endocytic dynamics across the plasma membrane, termed as polarized membrane trafficking. Our preliminary data have shown that changes in membrane tension additionally result in the heterogeneous expression of two distinct adhesive structures during proliferation and nondirectional migration of breast cancer cells. Although membrane tension, endocytosis, adhesion, and cell migration have been extensively studied individually, it is unknown how these processes are collectively regulated by breast cancer cells to metastasize. We thus aim to develop experimental and analytical approaches that will allow us to monitor polarized membrane trafficking, the formation of adhesive structures, and membrane tension in several migrating breast epithelial cell lines. This involves using a microfluidic platform that simultaneously allows the leading and trailing edge of a cell to be separately treated during migration and enables the application of inputs native to the cellular microenvironment. Examination of the various regulatory pathways on the cell membrane that contribute to breast cancer metastasis will significantly impact the development of therapeutic targets in breast cancer drug discovery.

Tyrosine-targeted covalent inhibition of a tRNA synthetase aided by zinc ion

Aminoacyl-tRNA synthetases (AARSs), a family of essential protein synthesis enzymes, are attractive targets for drug development. Although several different types of AARS inhibitors have been identified, AARS covalent inhibitors have not been reported. Here we present five unusual crystal structures showing that threonyl-tRNA synthetase (ThrRS) is covalently inhibited by a natural product, obafluorin (OB). The residue forming a covalent bond with OB is a tyrosine in ThrRS active center, which is not commonly modified by covalent inhibitors. The two hydroxyl groups on the o-diphenol moiety of OB form two coordination bonds with the conserved zinc ion in the active center of ThrRS. Therefore, the β-lactone structure of OB can undergo ester exchange reaction with the phenolic group of the adjacent tyrosine to form a covalent bond between the compound and the enzyme, and allow its nitrobenzene structure to occupy the binding site of tRNA. In addition, when this tyrosine was replaced by a lysine or even a weakly nucleophilic arginine, similar bonds could also be formed. Our report of the mechanism of a class of AARS covalent inhibitor targeting multiple amino acid residues could facilitate approaches to drug discovery for cancer and infectious diseases.

Role and Application of Biocatalysts in Cancer Drug Discovery

A biocatalyst is an enzyme that speeds up or slows down the rate at which a chemical reaction occurs and speeds up certain processes by 108 times. It is used as an anticancer agent because it targets drug activation inside the tumor microenvironment while limiting damage to healthy cells. Biocatalysts have been used for the synthesis of different heterocyclic compounds and is also used in the nano drug delivery systems. The use of nano-biocatalysts for tumor-targeted delivery not only aids in tumor invasion, angiogenesis, and mutagenesis, but also provides information on the expression and activity of many markers related to the microenvironment. Iosmapinol, moclobemide, cinepazide, lysine dioxygenase, epothilone, 1-homophenylalanine, and many more are only some of the anticancer medicines that have been synthesised using biocatalysts. In this review, we have highlighted the application of biocatalysts in cancer therapies as well as the use of biocatalysts in the synthesis of drugs and drug-delivery systems in the tumor microenvironment.

A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology.

Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including population-trials as surrogate subjects in vivo. PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting "biological equivalence or interchangeability" between the two. Here we demonstrate the applications of PDXO biobank for HTS "matrix" screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of >550 matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.

Structure-based in silico investigation of antagonists of human ribonucleotide reductase from Annonamuricata

Human ribonucleotide reductase (HRR) also known as ribonuceotide diphosphate reductase catalyzes the conversion of ribonucleotide to deoxyribonuceotides which is the rate limiting step in the synthesis of DNA, establishing the enzyme as a vital therapeutic target in discovery of cancer drugs. Hence, this study aimed at predicting HRR inhibitor(s) from Annona muricata bioactive compounds. A library of one hundred and twenty-six (126) compounds from Annona muricata was screened against HRR via the glide model. Eight (8) leads were used for the molecular mechanics generalized born surface area (MM-GBSA), e-pharmacophore, quantitative structural activity relationship (QSAR), pharmacokinetics profile and the top scored compound for molecular dynamics (MD) simulation using the Maestro - Schrödinger suite (2017-1). The quantum mechanics calculation of the lead compounds was carried out using Spartan 10. The results of the molecular docking and MM-GBSA calculation revealed eight (8) lead compounds observed as potent antagonists of HRR with binding affinity ranging from −6.454 kcal/mol to −10.190 kcal/mol which are comparable to the reference drug (Gemcitabine) and co-crystalized ligand. These eight hit compounds showed high fitness score and pIC50 value from the e-pharmacophore and QSAR analysis respectively. The result of the density functional theory of the hit compounds revealed that, EHOMO values range from −5.38 eV to −5.83 eV suggesting the hit molecules as electron donor. This study has predicted eight compounds from A. muricata as inhibitors of HRR with the stability of the top-scored compound (myricetin)-protein complex validated via MD simulation. Hence, in vivo and in vitro experiments are proposed for the discovery of potent therapeutic agents in the management of cancer via human ribonucleotide reductase inhibition.

Current Trends in Computational Chemistry for Breast Cancer

Abstract: Cancer is a condition in which body cells grow uncontrollably and spread to other parts of the body or grow at a particular location. Depending on their location, cancer is named or categorized. Breast cancer is the second most constantly determined and one of the prime reasons for cancer death among females. Many external factors like carcinogenic agents and internal factors like genetic factors are responsible for causing breast cancer in females. Additionally, the threat of breast cancer occurrences increases with age and non-success in treatment. The current methods and treatments utilized in treating, diagnosing and predicating breast cancer in the present world are not very advanced. Therefore, over time, the desire to analyze the factors facilitating the succession of breast cancer, prediction, and reduction in the time taken for diagnostics, treatment, and drug discovery for breast cancer has increased. However, traditional methods make it hard to study prediction, diagnostics, treatment, and drug discovery for breasts. Therefore, computational approaches like artificial intelligence, bioinformatics, quantitative structure-activity relationship (QSAR) studies, and molecular docking are used to analyze those things. This article discusses current trends in computational chemistry in different fields.

Crystallographic fragment screening in academic cancer drug discovery.

Fragment-based drug discovery (FBDD) has brought several drugs to the clinic, notably to target proteins once considered to be challenging, or even undruggable. Screening in FBDD relies upon observing and/or measuring weak (millimolar-scale) binding events using biophysical techniques or crystallographic fragment screening. This latter structural approach provides no information about binding affinity but can reveal binding mode and atomic detail on protein-fragment interactions to accelerate hit-to-lead development. In recent years, high-throughput platforms have been developed at synchrotron facilities to screen thousands of fragment-soaked crystals. However, using accessible manual techniques it is possible to run informative, smaller-scale screens within an academic lab setting. This chapter describes general protocols for home laboratory-scale fragment screening, from fragment soaking through to structure solution and, where appropriate, signposts to background, protocols or alternatives elsewhere.

Efficient and environmentally friendly synthesis of 1,2,3-triazole derivatives via [3 + 2] cycloaddition and their potential as lung cancer inhibitors: An in silico study

A catalyst-free one-pot synthetic approach for the synthesis of substituted 1,2,3-triazole has been described. The reaction proceeds via the simple click chemistry as well as the formation of two new C-N bonds. A wide variety of substituted 1,2,3-triazoles were obtained in good yield by using both maleimides and 1,4-naphthoquinone as coupling partners. Moreover, one of our synthesised compounds has been confirmed by single-crystal XRD analysis. Molecular docking studies with EGFR-TK receptor revealed the lowest binding energy displayed by 5ba with a binding energy of −8.8 kcal/mol. Given all the simulation data, 18 out of 20 compounds possess promising anticancer activity against the 6TFU receptor. This inhibition property is improved efficiency than the commercially available drug Gefitinib and thus can be an excellent lead compound for cancer drug discovery.

2nd International Scientific Conference of the The Malaysian Association for Cancer Research (MACR)

The Malaysian Association for Cancer Research (MACR) is proud to organize the second instalment of MACR International Scientific Conference (MSC) in partnership with Malaysian Oncological Society (MOS) and local Public & Private universities. MSC aims to provide a major convening platform for cancer research communities based locally and abroad. This two-day conference is expected to open up avenues for meaningful collaboration at the regional and global levels to promote cancer drug discovery and development through integrative research.The topics this conference will cover include but are not limited to: Novel cancer drug target identification, New cancer drug discoveries, Translational cancer medicine, Clinical trials of new cancer drugs, Diagnostic and prognostic values of new cancer markers, Cancer prevention, and Precision oncology. Download the published abstract (please click on the PDF file right side of this abstract)

Discovery of Pongol, the Furanoflavonoid, as an Inhibitor of CDK7/Cyclin H/MAT1 and Its Preliminary Structure-Activity Relationship.

Natural products have been a great source of leads for cancer drug discovery. The cyclin-dependent kinases (CDKs) play a vital role in the initiation and progression of cancer. The CDK-activating kinase, CDK7/cyclin H/MAT1, has recently gained tremendous attention in targeted cancer drug discovery. Herein, we screened a small library of pure natural products in an ADP-Glo CDK7/H kinase assay that yielded a series of furano- and naphthoflavonoids among actives. Pongol (SBN-88), the hydroxy-substituted furanoflavonoid, inhibits CDK7/H as well as CDK9/T1 with IC50 values of 0.93 and 0.83 μM, respectively, and >20-fold selectivity over CDK2/E1 (IC50 > 20 μM). The molecular docking and molecular dynamics simulation revealed that the presence of phenolic -OH in pongol is vital for kinase inhibition, as its absence resulted in a significant loss in activity (e.g., lanceolatin B). The prime MM-GBSA calculations revealed the presence of strong lipophilic and H-bonding interactions of pongol with CDKs.

Anticancer Potential of Rhychosia beddomei: An In vitro and In silico Study

Rhychosia beddomei is widely distributed in tropical and subtropical regions around the world. Traditionally this plant has been used as a medicine for multiple ailments including cancer. The present study addresses the evaluation of In vitro anticancer activity by using MTT Assay of methanolic extracts of whole plant of Rhychosia beddomei in Human Hepatocellular Carcinoma (HepG2) cell line in comparison with standard drug doxorubicin as well as In silico analysis. Doxorubicin acts in the cancer cell by intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair and generation of free radicals and their damage to cellular membranes, DNA and proteins. Cytotoxicity studies have indicated that the phytoconstituents of Rhychosia beddomei have the ability to selectively target cancer, whereas minimal or negligible cytotoxic effects were observed on normal cells. The molecular docking approach was employed to check binding conformations of phytochemicals against human cyclin-dependent kinase 2, CDK-2 and Topoisomerase-2, Topo-II proteins (Protein Data bank-ID: 1DI8 and 1ZXM) through Mcule online molecular modelling tool. The docking revealed an encouraging binding score with a maximum score of -11.5 and -10.4 kCal/mol with CDK-2 and Topo-II respectively and all the selected ligands indicate promising anticancer activity. Molecular docking studies using the phytoconstituents were performed in order to gain a better understanding of the putative mechanisms of action leading to the development of improved and affordable therapies. This study paves a way to better understand the integration of molecular docking and in vitro studies can accelerate cancer drug discovery showing a good consistency of anticancer therapeutic drug potentials of Rhychosia beddomei by In vitro and In silico approaches.

Cellular Genome-Scale Metabolic Modeling Identifies New Potential Drug Targets Against Hepatocellular Carcinoma.

Genome-scale metabolic modeling (GEM) is one of the key approaches to unpack cancer metabolism and for discovery of new drug targets. In this study, we report the Transcriptional Regulated Flux Balance Analysis-CORE (TRFBA-), an algorithm for GEM using key growth-correlated reactions using hepatocellular carcinoma (HCC), an important global health burden, as a case study. We generated a HepG2 cell-specific GEM by integrating this cell line transcriptomic data with a generic human metabolic model to forecast potential drug targets for HCC. A total of 108 essential genes for growth were predicted by the TRFBA-CORE. These genes were enriched for metabolic pathways involved in cholesterol, sterol, and steroid biosynthesis. Furthermore, we silenced a predicted essential gene, 11-beta dehydrogenase hydroxysteroid type 2 (HSD11B2), in HepG2 cells resulting in a reduction in cell viability. To further identify novel potential drug targets in HCC, we examined the effect of nine drugs targeting the essential genes, and observed that most drugs inhibited the growth of HepG2 cells. Some of these drugs in this model performed better than Sorafenib, the first-line therapeutic against HCC. A HepG2 cell-specific GEM highlights sterol metabolism to be essential for cell growth. HSD11B2 downregulation results in lower cell growth. Most of the compounds, selected by drug repurposing approach, show a significant inhibitory effect on cell growth in a wide range of concentrations. These findings offer new molecular leads for drug discovery for hepatic cancer while also illustrating the importance of GEM and drug repurposing in cancer therapeutics innovation.

CanSAR: update to the cancer translational research and drug discovery knowledgebase.

canSAR (https://cansar.ai) is the largest public cancer drug discovery and translational research knowledgebase. Now hosted in its new home at MD AndersonCancer Center,canSAR integrates billions of experimental measurements from across molecular profiling, pharmacology, chemistry, structural and systems biology. Moreover, canSAR applies a unique suite of machine learning algorithms designed to inform drug discovery. Here, we describe the latest updates to the knowledgebase, including a focus on significant novel data. These include canSAR's ligandability assessment of AlphaFold; mapping of fragment-based screening data; and new chemical bioactivity data for novel targets. We also describe enhancements to the data and interface.

Synthesis and Characterization of Griseofulvin Derivatives as Microtubule‐Stabilizing Agents

AbstractMicrotubules have been an attractive target of cancer drug discovery due to their highly dynamic nature during mitosis. Griseofulvin, a natural antifungal compound, is known to interfere with microtubule dynamics. In the present study, we prepared and analyzed twenty‐seven novel griseofulvin derivatives. Three of these compounds had GI50 values <10 μM (5.74 to 9.7 μM) in breast cancer cell line CAL‐51. The most promising compound ((2S,6’R)‐4’‐(benzhydrylamino)‐7‐chloro‐4,6‐dimethoxy‐6’‐methyl‐3H‐spiro[benzofuran‐2,1’‐cyclohexan]‐3’‐ene‐2’,3‐dione), was characterized as a microtubule‐stabilizing agent with a GI50 value of 5.74±1.43 μM compared to 10.79±3.06 μM GI50 for parental griseofulvin. It also inhibited the proliferation of other cancer cell lines, including KB‐3‐1 and HCT116, with GI50 values of 1.19±0.34 μM and 2.48±0.40 μM, respectively. Treatment of cancer cells with it resulted in aberrant mitosis causing G2/M arrest. Finally, we show that this compound increased the expression of p53 protein and induced apoptotic cell death.