Intersubunit Coupling Enables Fast CO2-Fixation by Reductive Carboxylases.

Enoyl-CoA carboxylases/reductases (ECRs) are some of the most efficient CO2-fixing enzymes described to date. However, the molecular mechanisms underlying the extraordinary catalytic activity of ECRs on the level of the protein assembly remain elusive. Here we used a combination of ambient-temperature X-ray free electron laser (XFEL) and cryogenic synchrotron experiments to study the structural organization of the ECR from Kitasatospora setae. The K. setae ECR is a homotetramer that differentiates into a pair of dimers of open- and closed-form subunits in the catalytically active state. Using molecular dynamics simulations and structure-based mutagenesis, we show that catalysis is synchronized in the K. setae ECR across the pair of dimers. This conformational coupling of catalytic domains is conferred by individual amino acids to achieve high CO2-fixation rates. Our results provide unprecedented insights into the dynamic organization and synchronized inter- and intrasubunit communications of this remarkably efficient CO2-fixing enzyme during catalysis.

Discovery of Azaindolin-2-One as a Dual Inhibitor of GSK3ß and Tau Aggregation with Potential Neuroprotective Activity.

The inhibition of glycogen synthase kinase 3ß (GSK3ß) activity through pharmacological intervention represents a promising approach for treating challenging neurodegenerative disorders like Alzheimer's disease. Similarly, abnormal tau aggregate accumulation in neurons is a hallmark of various neurodegenerative diseases. We introduced new dual GSK3ß/tau aggregation inhibitors due to the excellent clinical outcome of multitarget drugs. Compound (E)-2f stands out among the synthesized inhibitors as a promising GSK3ß inhibitor (IC50 1.7 µM) with a pronounced tau anti-aggregation effect in a cell-based model of tauopathy. Concurrently, (E)-2f was demonstrated to be non-toxic to normal cells, making it a promising neuroprotective lead compound that needs further investigation.

EGFR-Targeted Pentacyclic Triterpene Analogues for Glioma Therapy.

Glioma, particularly its most malignant form, glioblastoma multiforme (GBM), is the most common and aggressive malignant central nervous system tumor. The drawbacks of the current chemotherapy for GBM have aroused curiosity in the search for targeted therapies. Aberrantly overexpressed epidermal growth factor receptor (EGFR) in GBM results in poor prognosis, low survival rates, poor responses to therapy and recurrence, and therefore EGFR-targeted therapy stands out as a promising approach for the treatment of gliomas. In this context, a series of pentacyclic triterpene analogues were subjected to in vitro and in silico assays, which were conducted to assess their potency as EGFR-targeted anti-glioma agents. In particular, compound 10 was the most potent anti-glioma agent with an IC50 value of 5.82 µM towards U251 human glioblastoma cells. Taking into account its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), compound 10 exerts selective antitumor action towards Jurkat human leukemic T-cells. This compound also induced apoptosis and inhibited EGFR with an IC50 value of 9.43 µM compared to erlotinib (IC50 = 0.06 µM). Based on in vitro and in silico data, compound 10 stands out as a potential orally bioavailable EGFR-targeted anti-glioma agent endowed with the ability to cross the blood-brain barrier (BBB).

Design, synthesis and investigation of the mechanism of action underlying anti-leukemic effects of the quinolinequinones as LY83583 analogs.

Literature conclusively shows that one of the quinolinequinone analogs (6-anilino-5,8-quinolinequinone), referred to as LY83583 hereafter, an inhibitor of guanylyl cyclase, was used as the inhibitor of the cell proliferation in cancer cells. In the present work, a series of analogs of the LY83583 containing alkoxy group(s) in aminophenyl ring (AQQ1-15) were designed and synthesized via a two-step route and evaluated for their in vitro cytotoxic activity against four different cancer cell lines (K562, Jurkat, MT-2, and HeLa) and human peripheral blood mononuclear cells (PBMCs) by MTT assay. The analog (AQQ13) was identified to possess the most potent cytotoxic activity against K562 human chronic myelogenous (CML) cell line (IC50 = 0.59 ± 0.07 µM) with significant selectivity (SI = 4.51) compared to imatinib (IC50 = 5.46 ± 0.85 µM; SI = 4.60). Based on its superior cytotoxic activity, the analog AQQ13 was selected for further mechanistic studies including determination of its apoptotic effects on K562 cell line via annexin V/ethidium homodimer III staining potency, ABL1 kinase inhibitory activity, and DNA cleaving capacity. Results ascertained that the analog AQQ13 induced apoptosis in K562 cell line with notable DNA-cleaving activity. However, AQQ13 demonstrated weak ABL1 inhibition indicating the correlation between anti-K562 and anti-ABL1 activities. In continuance, respectively conducted in silico molecular docking and Absorption, Distribution, Metabolism, and Excretion (ADME) studies drew attention to enhanced binding interactions of AQQ13 towards DNA and its high compatibility with the potential limits of specified pharmacokinetic parameters making it as a potential anti-leukemic drug candidate. Our findings may provide a new insight for further development of novel quinolinequinone-based anticancer analogs against CML.

Structure based design, synthesis, and evaluation of anti-CML activity of the quinolinequinones as LY83583 analogs.

Quinone-based small molecules are the promising structures for antiproliferative drug design and can induce apoptosis in cancer cells. Among them, one of the quinolinequinones, named as 6-anilino-5,8-quinolinequinone, LY83583 has the ability to inhibit the growth of cancer cells as an inhibitor of cyclase. The biological potential of all synthesized compounds as the analogs of the identified lead molecule LY83583 that possessed the antiproliferative efficiency was determined. The two series of the LY83583 analogs containing electron-withdrawing or electron-donating group(s) were synthesized and subsequently in vitro evaluated for their cytotoxic activity against K562, Jurkat, MT-2, and HeLa cell lines using MTT assay. All the LY83583 analogs showed antiproliferative activity with good IC50 values (less than positive control imatinib). Four analogs from each series were also selected for the determination of selectivity against human peripheral blood mononuclear cells (PBMCs). The analog AQQ15 showed high potency towards all cancer cell lines with almost similar selectivity of imatinib. In order to get a better insight into cytotoxic effects of the analog AQQ15 in K562 cells, further apoptotic effects due to annexin V/ethidium homodimer III staining, ABL1 kinase inhibition, and DNA cleaving ability were examined. The analog AQQ15 induced apoptotic cell death in K562 cells with 34.6% compared to imatinib (6.5%). This analog showed no considerable ABL1 kinase inhibitory activity but significant DNA cleavage activity indicating DNA fragmentation-induced apoptosis. Besides, molecular docking studies revealed that the analog AQQ15 established proper interactions with the deoxyribose sugar attached with the nucleobases adenine and guanidine respectively, in the minor groove of the double helix of DNA. In silico predicted pharmacokinetic parameters of this analog were found to comply with the standard range making it an efficient anticancer drug candidate for further research.

A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors.

BACKGROUND: After the approval of imatinib, more than 25 antitumor agents targeting kinases have been approved, and several promising candidates are at various stages of clinical evaluation. OBJECTIVES: Due to the importance of the thiazole scaffold in targeted anticancer drug discovery, the goal of this work is to identify new thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of Chronic Myeloid Leukemia (CML). METHODS: New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on the K562 CML cell line. Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic effects on Mitogen-Activated Peripheral Blood Mononuclear Cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory effects on eight different Tyrosine Kinases (TKs), including ABL1 kinase. In order to investigate the binding mode of compound 2j into the ATP binding site of ABL1 kinase (PDB: 1IEP), a molecular docking study was conducted using MOE 2018.01 program. The QikProp module of Schrödinger's Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p. RESULTS: 4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 µM similar to imatinib (IC50= 6.84±1.11µM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound 2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17µM). According to molecular docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase, forming significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's rule of five and Jorgensen's rule of three. CONCLUSION: Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.

In Vitro and In Silico Evaluation of Anticancer Activity of New Indole-Based 1,3,4-Oxadiazoles as EGFR and COX-2 Inhibitors.

Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are crucial targetable enzymes in cancer management. Therefore, herein, new 2-[(5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(thiazol/benzothiazol-2-yl)acetamides (2a-i) were designed and synthesized as EGFR and COX-2 inhibitors. The cytotoxic effects of compounds 2a-i on HCT116 human colorectal carcinoma, A549 human lung adenocarcinoma, and A375 human melanoma cell lines were determined using MTT assay. 2-[(5-((1H-Indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(6-ethoxybenzothiazol-2-yl)acetamide (2e) exhibited the most significant anticancer activity against HCT116, A549, and A375 cell lines with IC50 values of 6.43 ± 0.72 µM, 9.62 ± 1.14 µM, and 8.07 ± 1.36 µM, respectively, when compared with erlotinib (IC50 = 17.86 ± 3.22 µM, 19.41 ± 2.38 µM, and 23.81 ± 4.17 µM, respectively). Further mechanistic assays demonstrated that compound 2e enhanced apoptosis (28.35%) in HCT116 cells more significantly than erlotinib (7.42%) and caused notable EGFR inhibition with an IC50 value of 2.80 ± 0.52 µM when compared with erlotinib (IC50 = 0.04 ± 0.01 µM). However, compound 2e did not cause any significant COX-2 inhibition, indicating that this compound showed COX-independent anticancer activity. The molecular docking study of compound 2e emphasized that the benzothiazole ring of this compound occupied the allosteric pocket in the EGFR active site. In conclusion, compound 2e is a promising EGFR inhibitor that warrants further clinical investigations.

Structure activity study of S-trityl-cysteamine dimethylaminopyridine derivatives as SIRT2 inhibitors: Improvement of SIRT2 binding and inhibition.

Sirtuin proteins are a highly conserved class of nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases. The pleiotropic human isoform 2 of Sirtuins (SIRT2) has been engaged in the pathogenesis of cancer in a plethora of reports around the globe. Thus, SIRT2 modulation is deemed as a promising approach for pharmaceutical intervention. Previously, we reported S-Trityl-l-Cysteine (STLC)-ornamented dimethylaminopyridine chemical entity named STC4 with a significant SIRT2 inhibitory capacity; this was separate from the conventional application of STLC scaffold as a kinesin-5 inhibitor. An interactive molecular docking study of SIRT2 and STC4 showed interaction between Asn168 of SIRT2 and the methyl ester of STC4, that appears to hinder STC4 to reach the selective pocket of the protein unlike strong SIRT2 inhibitor SirReal2. To improve its activity, herein, we utilized S-trityl cysteamine pharmacophore lacking the methyl ester. Nine compounds were synthesized and assayed affording three biopertinent SIRT2 inhibitors, and two of them, STCY1 and STCY6 showed higher inhibitory activity than STC4. These compounds have pronounced anti-proliferative activities against different cancer cell lines. A molecular docking study was executed to shed light on the supposed binding mode of the lead compound, STCY1, into the selective pocket of SIRT2 by interaction of the nitrogen of pyridine ring of the compound and Ala135 of the protein. The outcome of the study exposes that the active compounds are effective intermediates to construct more potent biological agents.

Anticancer activity of Turkish marine extracts: a purple sponge extract induces apoptosis with multitarget kinase inhibition activity.

Marine natural products have drawn a great deal of attention as a vital source of new drugs for the last five decades. However, marine organisms in the seas surrounding Turkey (the Black Sea, the Aegean Sea and the Mediterranean Sea) haven't been yet extensively explored. In the present study, three marine organisms (Dysidea avara, Microcosmus sabatieri and Echinaster sepositus) were sampled from the Dardanelles (Turkish Straits System, Western Turkey) by scientific divers, transferred to the laboratory and then were extracted with 70% ethanol. The extracts were tested for their cytotoxic effect against K562, KMS-12PE, A549, and A375 cancer cell lines. The sponge extract elicited the most promising cytotoxic activity, thus it was further evaluated against H929, MCF-7, HeLa, and HCT116 cancer cells. Most of the designated cells showed a considerable sensitivity for the sponge extract particularly H929, K562, KMS-12PE and HeLa cells with IC50 less than 10 µg/mL. On the contrary, the other two extracts exhibited no cytotoxic activity on all cells at 100 µg/mL concentration. The sponge extract was tested for its capacity to induce apoptosis in cancer cells and to inhibit a panel of tyrosine kinases showing remarkable results. The outcome of this study represents a platform for discovery of new chemotherapeutic agents of marine natural origin.

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity.

Herein, we report the synthesis and cytotoxic effects of novel chlorinated plastoquinone analogs (ABQ1-17) against different leukemic cells. Compounds ABQ3, ABQ11, and ABQ12 demonstrated a pronounced antiproliferative effect against chronic myelogenous leukemia (CML) K562 cell line with IC50 values of 0.82 ± 0.07, 0.28 ± 0.03, and 0.98 ± 0.22 µM, respectively. Among them, ABQ11 showed approximately three times higher selectivity than imatinib on CML. ABQ11-treated CML cells induced significant apoptosis at low concentration. Inhibitory effect of ABQ11 against eight different tyrosine kinases, including ABL1, was investigated. ABQ11 inhibited ABL1 with IC50 value of 13.12 ± 1.71 µM, indicating that the moderate inhibition of ABL1 kinase is just an in-part mechanism of its outstanding cellular activity. Molecular docking of ABQ11 into ABL1 kinase ATP-binding pocket revealed the formation of some key interactions. Furthermore, DNA cleavage assay showed that ABQ11 strongly disintegrated DNA at 1 µM concentration in the presence of iron (II) complex system, assuming that the major mechanism for the anticancer effects of ABQ11 is DNA cleavage. In silico ADMET prediction revealed that ABQ11 is a drug-like small molecule with a favorable safety profile. Taken together, ABQ11 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from imatinib.

Antileukemic Activity of Twig Components of Caucasian Beech in Turkey.

Despite the development of a range of anti-cancer agents, cancer diagnoses are still increasing in number, remaining a leading cause of death. Anticancer drug treatment is particularly important for leukemia. We screened Turkish plants and found the unique antileukemic activity of twig components in Turkish Caucasian beech, selectively inducing apoptosis in leukemia cells. This effect is unique among some kinds of beeches, presumably related to oxidative stress. This study would lead to effective use of discarded material, i.e., twig of beech, and a new anti-leukemic drug based on large tree.

Discovery and structure-activity relationship of plastoquinone analogs as anticancer agents against chronic myelogenous leukemia cells.

Two series of amino-1,4-benzoquinones (AQ1-18) based on the structural analogs of plastoquinones were synthesized and the structure-activity relationship against chronic myelogenous leukemia activity was examined. All of the synthesized compounds were tested for their cytotoxic effects on different leukemic cell lines. Of interest, AQ15 exhibited a better selectivity than the reference drug imatinib on cancer cells. Owing to this, AQ15 was selected for a further apoptosis/necrosis evaluation where AQ15-treated K562 cells demonstrated similar apoptotic effects like imatinib-treated cells at their IC50 values. The inhibitory effects of AQ15 and the other three compounds with various activities against eight tyrosine kinases, including ABL1, were investigated. AQ15 showed weak activity against ABL1, and a correlation was observed between the anti-K562 and anti-ABL1 activities. The binding mode of AQ15 into the ATP binding pocket of ABL1 kinase was predicted in silico, showing the formation of some key interactions. In addition, AQ15 was shown to suppress the downstream signaling of BCR-ABL in K562 cells. Finally, AQ15 obviously cleaved DNA in the presence of an iron(II) complex system, indicating that this can be the major mechanism of its antiproliferative action, whereas the mild inhibition of ABL kinase is just in-part mechanism of its overall outstanding cellular activity.

Design, synthesis, and biological activity of Plastoquinone analogs as a new class of anticancer agents.

In this paper, based on Plastoquinone (PQ) analogs possessing substituted aniline containing alkoxy group(s), new 2,3-dimethyl-5-amino-1,4-benzoquinones (PQ1-15) were designed and synthesized in either two steps or one-pot reaction. Specifically, the substituted amino moiety containing mono or poly alkoxy group(s) with various positions and groups were mainly explored to understand the structure-activity relationships for the cytotoxic activity against three human cancer cell lines (K562, Jurkat, and MT-2) and human peripheral blood mononuclear cells (PBMC). PQ2 was found to be most effective anticancer compound on K562 and Jurkat cell lines with IC50 values of 6.40 ±â€¯1.73 µM and 7.72 ±â€¯1.49 µM, respectively. Interestingly, the compound was non-cytotoxic to normal PBMC and also MT-2 cancer cells. PQ2 which showed significant selectivity in MTT assay was chosen for apoptotic/necrotic evaluation and results exhibited that it induced apoptosis in K562 cell line after 6 h of treatment. PQ2 showed anti-Abelson kinase 1 (Abl1) activity with different inhibitory profile than Imatinib in the panel of eight kinases. The binding mode of PQ2 into Abl ATP binding pocket was predicted in silico showing the formation of some key interactions. In addition, PQ2 induced Bcr-Abl1 mediated ERK pathway in human chronic myelogenous leukemia (CML) cells. Furthermore, DNA-cleaving capability of PQ2 was clearly enhanced by iron (II) complex system. Afterward, a further in silico ADMET prediction revealed that PQ2 possesses desirable drug-like properties and favorable safety profile. These results indicated that PQ2 has multiple mechanism of action and two of them are anti-Bcr-Abl1 and DNA-cleaving activity. This study suggests that Plastoquinone analogs could be potential candidates for multi-target anticancer therapy.

Antiproliferative S-Trityl-l-Cysteine -Derived Compounds as SIRT2 Inhibitors: Repurposing and Solubility Enhancement.

S-trityl-l-cysteine (STLC) is a well-recognized lead compound known for its anticancer activity owing to its potent inhibitory effect on human mitotic kinesin Eg5. STLC contains two free terminal amino and carboxyl groups that play pivotal roles in binding to the Eg5 pocket. On the other hand, such a zwitterion structure complicates the clinical development of STLC because of the solubility issues. Masking either of these radicals reduces or abolishes STLC activity against Eg5. We recently identified and characterized a new class of nicotinamide adenine dinucleotide-dependent deacetylase isoform 2 of sirtuin protein (SIRT2) inhibitors that can be utilized as cytotoxic agents based on an S-trityl-l-histidine scaffold. Herein, we propose new STLC-derived compounds that possess pronounced SIRT2 inhibition effects. These derivatives contain modified amino and carboxyl groups, which conferred STLC with SIRT2 bioactivity, representing an explicit repurposing approach. Compounds STC4 and STC11 exhibited half maximal inhibitory concentration values of 10.8 ± 1.9 and 9.5 ± 1.2 µM, respectively, against SIRT2. Additionally, introduction of the derivatizations in this study addressed the solubility limitations of free STLC, presumably due to interruption of the zwitterion structure. Therefore, we could obtain drug-like STLC derivatives that work by a new mechanism of action. The new derivatives were designed, synthesized, and their structure was confirmed using different spectroscopic approaches. In vitro and cellular bioassays with various cancer cell lines and in silico molecular docking and solubility calculations of the synthesized compounds demonstrated that they warrant attention for further refinement of their bioactivity.

Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors.

Epidermal growth factor receptor (EGFR, also known as HER1) and HER2, prominent members of receptor tyrosine kinase (RTK) superfamily, have been reported as diagnostic or prognostic markers in tumor progression. Based on the importance of molecular hybridization of pyrazoline and thiazole scaffolds in the discovery of potent anticancer agents, new thiazolyl-pyrazoline derivatives (3a-v) were synthesized and screened for their cytotoxic effects on A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma and A375 human melanoma cell lines. 1-(4-(4-Fluorophenyl)thiazol-2-yl)-3-(4-morpholinophenyl)-5-(4-chlorophenyl)-2-pyrazoline (3c),1-(4-(4-cyanophenyl)thiazol-2-yl)-3-(4-morpholinophenyl)-5-(4-chlorophenyl)-2-pyrazoline (3f) and 1-(4-(4-cyanophenyl)thiazol-2-yl)-3-(4-piperidinophenyl)-5-(4-chlorophenyl)-2-pyrazoline (3q) were found as the most potent anticancer agents against A549 and MCF-7 cell lines compared to erlotinib. Compound 3q also showed moderate cytotoxic activity against A375 cell line. Moreover, these compounds exert a cancer cell-selective action against Jurkat cell line posing no toxicity on peripheral blood mononuclear cells (PBMCs). In order to enlighten the mechanism of action underlying anticancer activity, compounds 3c, 3f and 3q were investigated for their apoptotic effects on A549 and MCF-7 cell lines and inhibitory potencies against eight different RTKs including EGFR and HER2 compared to erlotinib. The results indicated that compounds 3f and 3q induced apoptosis in both cell lines and showed significant EGFR inhibitory activity with IC50 values of 4.34 ±â€¯0.66 µM and 4.71 ±â€¯0.84 µM, respectively when compared with erlotinib (IC50 = 0.05 ±â€¯0.01 µM). Besides, compound 3f also inhibited HER2 notably with an IC50 value of 2.28 ±â€¯0.53 µM making it a dual EGFR and HER2 inhibitor. Molecular docking studies, which were conducted to support the in vitro assays, pointed out that compound 3f showed high affinity into the ATP binding sites of EGFR and HER2.

New SIRT2 inhibitors: Histidine-based bleomycin spin-off.

Bleomycin is considered to exert its antitumor activity via DNA cleavage mediated by activated oxygen generated from the iron complex in its chelator moiety. Spin-offs from this moiety, HPH-1Trt and HPH-2Trt, with anti-cancer activities were recently synthesized. In this paper, we developed inhibitors of nicotinamide adenine dinucleotide-dependent deacetylase isoform 2 of Sirtuin protein (SIRT2), based on HPH-1Trt/HPH-2Trt, and aimed to generate new anti-cancer drugs. HPH-1Trt and HPH-2Trt had in vitro anti-SIRT2 inhibitory activity with 50% inhibitory concentration (IC50) values of 5.5 and 8.8 µM, respectively. A structural portion of HPH-1Trt/HPH-2Trt, a tritylhistidine derivative TH-1, had stronger activity (IC50 = 1.7 µM), and thus, fourteen derivatives of TH-1 were synthesized. Among them, TH-3 had the strongest activity (IC50 = 1.3 µM). Selective binding of TH-3 in the pocket of SIRT2 protein was confirmed with a molecular docking study. Furthermore, TH-3 strongly lowered viability of the breast cancer cell line MCF7 with an IC50 of 0.71 µM. A structure-activity relationship study using cell lines suggested that the mechanism of TH-3 to suppress MCF7 cells involves not only SIRT2 inhibition, but also another function. This compound may be a new candidate anti-cancer drug.