Leukemia Cancer Cell Lines Research Articles

The 5-hydrazino-3-methylisothiazole-4-carboxylic acid, its new 5-substituted derivatives and their antiproliferative activity

Currently, the basic method of treatment of colon cancer is surgery. The range of anticancer drugs used in the treatment of colorectal cancer is small and is based mainly on systemic combination chemotherapy. As a result of the designed syntheses, we received new isothiazole derivatives with anticancer activity. The synthesized 5-hydrazino-3-methylisothiazole-4-carboxylic acid has never been obtained before. It is also a substrate for the synthesis of its innovative derivatives, i.e. compounds that are Schiff bases. The identification of the structure of new compounds was carried out using mass spectrometry (MS), proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR) and infrared spectroscopy (IR). Potential antitumor activity was confirmed in antiproliferative MTT and SRB tests. The selected, most biologically active substances were characterized by high selectivity towards leukemia and colon cancer cell lines. They caused high inhibition of proliferation of human biphenotypic B cell myelomonocytic leukemia MV4-11 (13 compounds), human colon adenocarcinoma cell lines sensitive LoVo (8 compounds) and resistant to doxorubicin LoVo/DX (12 compounds). However, in the conducted studies, their activity against breast adenocarcinoma MCF-7 and normal non-tumorigenic epithelial cell line derived from mammary gland MCF-10A was substantially lower. The result of this work is claimed Polish patent application.

Exploiting the 7-methylimidazo[1,5-a]pyrazin-8(7H)-one scaffold for the development of novel chemical inhibitors for Bromodomain and Extraterminal Domain (BET) family

The bromodomain and extraterminal (BET) family of proteins play a crucial role in promoting gene expression of critical oncogenes. Novel BET bromodomain inhibitors with excellent potency, drug metabolism and pharmacokinetics (DMPK) properties were in strong need for development. We reported a series of potential BET inhibitors through incorporation of imidazole into pyridine scaffold. Among them, a novel BET inhibitor with 7-methylimidazo[1,5-a]pyrazin-8(7H)-one core, compound 28, was considered to be the most promising for in-depth study. Compound 28 exhibited excellent BRD4-inhibitory activity with IC50 value of 33 nM and anti-proliferation potency with IC50 value of 110 nM in HL-60 (human promyelocytic leukemia) cancer cell lines. Western Blot indicated that compound 28 can effectively trigger apoptosis in BxPc3 cells by modulating the intrinsic apoptotic pathway. In conclusion, these results suggested that compound 28 has merely potential for leukemia treatment.

Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells

BackgroundLactobacillus plantarum, a major species of Lactic Acid Bacteria (LAB), are capable of producing postbiotic metabolites (PM) with prominent probiotic effects that have been documented extensively for rats, poultry and pigs. Despite the emerging evidence of anticancer properties of LAB, very limited information is available on cytotoxic and antiproliferative activity of PM produced by L. plantarum. Therefore, the cytotoxicity of PM produced by six strains of L. plantarum on various cancer and normal cells are yet to be evaluated.MethodsPostbiotic metabolites (PM) produced by six strains of L. plantarum were determined for their antiproliferative and cytotoxic effects on normal human primary cells, breast, colorectal, cervical, liver and leukemia cancer cell lines via MTT assay, trypan blue exclusion method and BrdU assay. The toxicity of PM was determined for human and various animal red blood cells via haemolytic assay. The cytotoxicity mode was subsequently determined for selected UL4 PM on MCF-7 cells due to its pronounced cytotoxic effect by fluorescent microscopic observation using AO/PI dye reagents and flow cytometric analyses.ResultsUL4 PM exhibited the lowest IC50 value on MCF-7, RG14 PM on HT29 and RG11 and RI11 PM on HL60 cell lines, respectively from MTT assay. Moreover, all tested PM did not cause haemolysis of human, dog, rabbit and chicken red blood cells and demonstrated no cytotoxicity on normal breast MCF-10A cells and primary cultured cells including human peripheral blood mononuclear cells, mice splenocytes and thymocytes. Antiproliferation of MCF-7 and HT-29 cells was potently induced by UL4 and RG 14 PM respectively after 72 h of incubation at the concentration of 30% (v/v). Fluorescent microscopic observation and flow cytometric analyses showed that the pronounced cytotoxic effect of UL4 PM on MCF-7 cells was mediated through apoptosis.ConclusionIn conclusion, PM produced by the six strains of L. plantarum exhibited selective cytotoxic via antiproliferative effect and induction of apoptosis against malignant cancer cells in a strain-specific and cancer cell type-specific manner whilst sparing the normal cells. This reveals the vast potentials of PM from L. plantarum as functional supplement and as an adjunctive treatment for cancer.

Novel Conjugated Unsaturated Ketones with Submicromolar Potencies Towards some Leukemic and Colon Cancer Cells.

Cancer continues to be the major health burden worldwide. There is an urgent need for the development of novel antineoplastic compounds to treat this devastating condition. Various alkylating anticancer drugs have been employed in the clinic for treating cancers. Unsaturated conjugated ketones are a group of alkylators which are of significant interest as potent antineoplastic agents. The goal of this study is to discover unsaturated conjugated ketones which are novel potent cytotoxins displaying growth-inhibitory properties towards neoplasms and also to serve as cytotoxic warheads in drug development. A variety of 3,5-bis (benzylidene)-4-piperidones 2a-n were synthesized and evaluated against a number of neoplastic cell lines. The short-term neurotoxicity of 2a-k, n was evaluated in mice by i.p. administration using doses level of 30, 100 and 300 mg/kg. Statistical correlations for determining structure-activity relationships were performed using an SPSS software. A number of compounds display cytotoxic potencies in the region of 10-7 to 10-8 M and some of the structural features contributing to the cytotoxicity were identified. Compounds 2a-d, 2h demonstrated substantially higher cytotoxic potencies compared to melphalan and 5- fluorouracil against a panel of leukemic and colon cancer cell lines. These lead cytotoxins comply with drug-likeness properties. In general, the antineoplastics 2 are well tolerated in mice using a short-term neurotoxicity screening. In general, this group of compounds comprises excellent cytotoxic agents, which warrant their further development as cytotoxic warheads.

Indole hybridized diazenyl derivatives: synthesis, antimicrobial activity, cytotoxicity evaluation and docking studies

BackgroundIn search of effective antimicrobial and cytotoxic agents, a series of indole hybridized diazenyl derivatives (DS-1 to DS-21) was efficiently prepared by condensation of diazotized p-aminoacetophenone with indole or nitroindole followed by reaction with different aromatic/heteroaromatic amines of biological significance. The synthesized derivatives were characterized by various spectroscopic techniques.MethodologyThe antimicrobial evaluation of DS-1 to DS-23 was done by tube dilution method against various pathogenic bacterial and fungal strains. The active antimicrobial derivatives were further evaluated for cytotoxicity against human lung carcinoma cell line (HCT-116), breast cancer cell line (MDAMB231), leukemic cancer cell line (K562), and normal cell line (HEK293) by MTT assay using doxorubicin as the standard drug. The test derivatives were additionally docked for the B-subunit of enzyme DNA gyrase from E. coli at the ATPase binding site to study the molecular interactions using Schrodinger maestro v11.5 software.Results and discussionMost of the synthesized derivatives have shown high activity against Gram-negative bacteria particularly E. coli and K. pneumonia with MIC ranging from 1.95 to 7.81 μg/ml. The derivatives have demonstrated very less activity against tested Gram positive bacterial and fungal strains. The derivatives DS-14 and DS-20 have been found to active against breast cancer cell line and human colon carcinoma cell line having IC50 in the range of 19–65 µg/ml. All the derivatives were found to less potent against leukemic cancer cell line. The synthesized derivatives have revealed their safety by exhibiting very less cytotoxicity against the normal cell line (HEK-293) with IC50 > 100 µg/ml. Most of the active derivatives have shown good docking scores in comparison to the standard drugs against DNA gyrase from E. coli. Further ADME predictions by Qikprop module of the Schrodinger confirmed these molecules have drug like properties.ConclusionThe derivatives DS-14 and DS-20 have shown potential against Gram-negative bacteria and breast cancer cell line and can be used as a lead for rational drug designing of the antimicrobial and cytotoxic agents..

In vitro and computational studies showed that perezone inhibits PARP-1 and induces changes in the redox state of K562 cells

Cancer is one of the leading causes of morbidity and mortality worldwide. This disease is characterized by uncontrolled growth and proliferation of abnormal cells with a high probability to develop metastasis. Recently, it was demonstrated that perezone, a sesquiterpene quinone, is capable to induce cell death in leukemia (K562), prostate (PC-3), colorectal (HCT-15) and lung (SKLU-1) cancer cell lines; however, its mechanism of action is unknown. Therefore, in this study, in vitro and computational studies were performed to determine the mechanism of action of perezone. Firstly, changes in K562 cell viability, as well as changes in the redox status of the cell in response to treatment with several concentrations of perezone were analyzed. The type of cell death induced, and the modification of the cell cycle were determined. In addition, MD simulations and docking studies were performed to investigate the interaction of perezone with seven regulators of the apoptotic process. Finally, the ability of perezone to inhibit PARP-1 was evaluated by in vitro studies. K562 cells treated with perezone exhibited decreased viability and more oxidized status, being this effect concentration-dependent. In addition, the increase of G0/G1 phase of cell cycle and apoptosis were observed. According to the performed computational studies conducted, perezone showed the highest affinity to PARP-1 enzyme being this complex the most stable due to the presence of a small and deep cavity in the active site, which allows perezone to fit deeply by forming hydrogen bonds and hydrophobic interactions, which drive this interaction. The activity of perezone as PARP-1 inhibitor was corroborated with an IC50 = 181.5 μM. The pro-apoptotic action of perezone may be related to PARP-1 inhibition and changes in the redox state of the cell. The obtained results allowed to understand the biological effect of perezone and, consequently, these could be employed to develop novel PARP-1 inhibitors.

Synthesis and In Vitro Antitumor Activity of Naringenin Oxime and Oxime Ether Derivatives.

Naringenin is one of the most abundant dietary flavonoids exerting several beneficial biological activities. Synthetic modification of naringenin is of continuous interest. During this study our aim was to synthesize a compound library of oxime and oxime ether derivatives of naringenin, and to investigate their biological activities. Two oximes and five oxime ether derivatives were prepared; their structure has been elucidated by NMR and high-resolution mass spectroscopy. The antiproliferative activity of the prepared compounds was evaluated by MTT assay against human leukemia (HL-60) and gynecological cancer cell lines isolated from cervical (HeLa, Siha) and breast (MCF-7, MDA-MB-231) cancers. Tert-butyl oxime ether derivative exerted the most potent cell growth inhibitory activity. Moreover, cell cycle analysis suggested that this derivative caused a significant increase in the hypodiploid (subG1) phase and induced apoptosis in Hela and Siha cells, and induced cell cycle arrest at G2/M phase in MCF-7 cells. The proapoptotic potential of the selected compound was confirmed by the activation of caspase-3. Antioxidant activities of the prepared molecules were also evaluated with xanthine oxidase, DPPH and ORAC assays, and the methyl substituted oxime ether exerted the most promising activity.

Synthesis, Characterization, Anticancer and In Silico ADME Properties of Caproic Acid Derivatives against P388 Cancer Cell Lines

The in-silico properties of absorption, distribution, metabolism, and excretion (ADME) and drugs likeness of caproic acid ester derivativeswere evaluated. The esterification of caproic acid from palm kernel oil with sitronelol and geraniol from citronella oil has been carried out using base (NaOH) catalyst. The cytotoxicity of ester compounds were also tested against P388 murine leukemia cancer cell lines using MTT method. Analysis of the ester productswere carried outusing spectroscopic (IR, MS and 1H-NMR) methods, which were confirmed that the desired compounds were successfully synthesized. Caproic acid ester derivatives showed higher anticancer activity compared to the parent caproic acid for P388 cancer cell lines. Citronellyl caproate with IC50 4.15x10-2µM has the strongeractivity than geranyl caproate with IC50 11x10-2 µM. ADME studies for the synthesized compounds revealed that the ester compounds have fulfill the Lipinski rule of five and has no carcinogenicity effect to rat or mouse.Key words: caproic acid, ester, P388, MTT, ADME

Semisynthetic aurones inhibit tubulin polymerization at the colchicine-binding site and repress PC-3 tumor xenografts in nude mice and myc-induced T-ALL in zebrafish

Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the leading, biologically active analogs were (Z)-2-((2-((1-ethyl-5-methoxy-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-6-yl)oxy)acetonitrile (5a) and (Z)-6-((2,6-dichlorobenzyl)oxy)-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (5b) that inhibited in vitro PC-3 prostate cancer cell proliferation with IC50 values below 100 nM. A xenograft study in nude mice using 10 mg/kg of 5a had no effect on mice weight, and aurone 5a did not inhibit, as desired, the human ether-à-go-go-related (hERG) potassium channel. Cell cycle arrest data, comparisons of the inhibition of cancer cell proliferation by aurones and known antineoplastic agents, and in vitro inhibition of tubulin polymerization indicated that aurone 5a disrupted tubulin dynamics. Based on molecular docking and confirmed by liquid chromatography-electrospray ionization-tandem mass spectrometry studies, aurone 5a targets the colchicine-binding site on tubulin. In addition to solid tumors, aurones 5a and 5b strongly inhibited in vitro a panel of human leukemia cancer cell lines and the in vivo myc-induced T cell acute lymphoblastic leukemia (T-ALL) in a zebrafish model.

A new pyridazinone exhibits potent cytotoxicity on human cancer cells via apoptosis and poly-ubiquitinated protein accumulation.

In the last 15years, pyridazinone derivatives have acquired extensive attention due to their widespread biological activities and pharmacological applications. Pyridazinones are well known for their anti-microbial, anti-viral, anti-inflammatory, anti-cancer, and cardiovascular activities, among others. In this study, we evaluated the anti-cancer activity of a new pyridazinone derivative and propose it as a potential anti-neoplastic agent in acute promyelocytic leukemia cells. Pyr-1 cytotoxicity was assessed on several human cancer and two non-cancerous cell lines by the DNS assay. Pyr-1 demonstrated potent cytotoxicity against 22 human cancer cell lines, exhibiting the most favorable selective cytotoxicity on leukemia (CEM and HL-60), breast (MDA-MB-231 and MDA-MB-468), and lung (A-549) cancer cell lines, when compared with non-cancerous breast epithelial MCF-10A cells. Analyses of apoptosis/necrosis pathways, reactive oxygen species (ROS) production, mitochondria health, caspase-3 activation, and cell cycle profile were performed via flow cytometry. Both hmox-1 RNA and protein expression levels were evaluated by quantitative real-time PCR and Western blotting assays, respectively. Pyr-1 induced apoptosis in acute promyelocytic leukemia cells as confirmed by phosphatidylserine externalization, mitochondrial depolarization, caspase-3 activation, DNA fragmentation, and disrupted cell cycle progression. Additionally, it was determined that Pyr-1 generates oxidative and proteotoxic stress by provoking the accumulation of ROS, resulting in the overexpression of the stress-related hmox-1 mRNA transcripts and protein and a marked increase in poly-ubiquitinated proteins. Our data demonstrate that Pyr-1 induces cell death via the intrinsic apoptosis pathway by accumulating ROS and by impairing proteasome activity.

Green synthesis of hematite (α-Fe2O3) nanoparticles using Rhus punjabensis extract and their biomedical prospect in pathogenic diseases and cancer

Hematite nanoparticles (NPs) are chemically and thermodynamically more stable among iron oxide NPs therefore these are considered highly suitable for biomedical applications. This work explores Rhus punjabensis extract potential as both reducing and capping agent for phytomediated synthesis of NPs from ferric chloride precursor. The structural, morphological and compositional investigations were carried out with XRD, SEM, TEM, EDS, and FFT. The synthesized NPs were hematite (Fe2O3) with rhombohedral crystal structure of an approximate size of 41.5 ± 5 nm. TEM, FTIR, and TG/DTA indicated phase-pure Fe2O3 formation with controlled size through use of capping agent. Biological activities depict that synthesized NPs had free radical scavenging, antioxidative potential and reducing power activities. These activities are due to phenolic and flavonoid like properties by attachment of different functional groups on the surface of NPs. The NPs exhibited significant Antileishmanial, antibacterial and protein kinase inhibition activities as compared with the corresponding plant extract. NPs depicted cytotoxic effect against HL-60 leukemic and DU-145 prostate cancer cell lines with ED50 values of 11.9 and 12.79 μg/ml, respectively. The inhibitory effect observed in the NF-κB assay suggested apoptotic potential of hematite NPs to cancerous cells. The green chemistry route reported in this paper for Fe2O3 NP synthesis can be safely and efficiently explored for treatment of cancer and as theranostic agent.

Synthesis of 5-(4-(1H-phenanthro[9,10-d]imidazol-2-yl)benzylidene)thiazolidine-2,4-dione as promising DNA and serum albumin-binding agents and evaluation of antitumor activity

A series of phenanthro[9,10-d]imidazole/oxazole and acenaphtho[1,2-d]imidazole with different aryl groups at C2-position has been synthesized. These compounds were in vitro evaluated for antitumor activity against a panel of 60 human cancer cell lines. Compound 8 exhibits higher cytotoxicity towards leukemia, colon, melanoma, renal, and breast cancer cell lines than the other evaluated cell panels and low toxicity against normal cell line Hek293. The binding properties of compound 8 with DNA have been investigated with absorption, emission and circular dichroism as well as thermal denaturation experiments which indicate intercalation with base pairs of human and calf thymus DNA. The molecular docking and site-selective binding studies also reveal the predominant intercalation of compound 8 in base pairs of DNA. The interaction between thiazolidine based phenanthrene 8 and serum albumins (HSA and BSA), transport proteins, has also been explored which shows quenching of fluorescence through static mechanism. The thermodynamic parameters, obtained from van't Hoff relationship indicate the prevalence of hydrogen-bonding/hydrophobic interactions for the binding phenomenon.

3-Hydroxyisoindolin-1-one derivates: Synthesis by palladium-catalyzed C[sbnd]H activation as BRD4 inhibitors against human acute myeloid leukemia (AML) cells

Bromodomain protein 4 (BRD4) is a member of the bromodomain and extra-terminal domain (BET) protein family, which plays a key role in transcriptional regulation. Recent biological and pharmacological studies have enabled linking of the BET bromodomains with diseases, including inflammation and cancer, suggesting that bromodomains are druggable targets. In this study, we made further structural modifications of our previously reported BRD4 inhibitors, to develop new chemical scaffold 3-Hydroxyisoindolin-1-One. Then a series of compounds (10a-q) were synthesized via palladium-catalyzed CH activation and BRD4-inhibitory activities and anti-proliferative effects of these compounds were evaluated. Compound 10e exhibited excellent BRD4-inhibitory activity with IC50 value of 80 nM and anti-proliferation potency with IC50 value of 365 nM in HL-60 (humanpromyelocytic leukemia) cancer cell lines. We have demonstrated compound 10e modulated the intrinsic apoptotic pathway. In conclusion, these results suggested that compound 10e could be utilized as a BRD4 inhibitor for further leukemia treatment.

Synthesis, characterization and molecular docking of new C,N‐palladacycles containing pyridinium‐derived ligands: DNA and BSA interaction studies and evaluation as anti‐tumor agents

Four new monomeric Pd (II) complexes with formulas [Pd(C,N)‐(2′‐NH2C6H4)C6H4 (N3)(L)] (A), (B) and [Pd(C,N)‐C6H4CH2NH(C4H9)(N3)(L)] (C), (D), [L = isonicotinamide for (A) and (C), L = 4‐N,N‐dimethylaminopyridine for (B) and (D)] have been synthesized using four initial dimers [Pd2{(C,N)‐(2′‐NH2C6H4)C6H4}2(μ‐OAc)2] (1), [Pd2{(C,N)‐ (2′‐NH2C6H4)C6H4}2(μ‐N3)2] (3) for A and C, and [Pd2{(C,N)‐C6H4CH2NH(C4H9)}2(μ‐OAc)2] (2) and [Pd2{(C,N)‐C6H4CH2NH(C4H9)}2(μ‐N3)2] (4) for B and D. Then synthesized complexes have been characterized by Fourier transform‐infrared, NMR spectroscopy and thermal gravimetric‐differential thermal analysis. Furthermore, UV–Vis spectroscopy, fluorescence spectroscopy, circular dichroism (CD) and helix melting temperature measurements have been employed to study the binding interaction of them with calf thymus‐deoxyribonucleic acid (DNA). The results reveal that all synthesized complexes can interact with DNA via groove‐binding mode. Bovine serum albumin (BSA)‐binding studies have been carried out using UV–Vis spectroscopy, emission titration and CD. However, competitive binding studies using warfarin, ibuprofen and digoxin on site markers demonstrated that the complexes bind to different sites on BSA. The results also indicated that the binding site was mainly located within site‐III for complex A, and site‐I for complexes B, C and D of BSA. In addition, molecular docking studies have been executed to determine the binding site of the DNA and BSA with complexes. Eventually, in vitro cytotoxicity of synthesized palladium complexes and cisplatin were carried out against human promyelocytic leukemia cancer (Hela) and breast cancer (MCF‐7) cell lines. Pursuant to the IC50 values, the cytotoxicity of complexes against MCF‐7 was more than Hela.

Investigation of Anticancer Activity of Lindernia crustacea (L.) F. Muell. var. Crustacean

Lindernia crustacea (L.) F. Muell. var. crustacean or “Ya Kap Hoi: YKH” was misunderstood as “Ya Yad Nam Kang” and cancer curative. This study aimed to investigate anticancer activity by the analysis of chemical constituent in extracts and in vitro screening of biological activities of the extract in several aspects such as cancer cell lines cytotoxic activity, immune cell proliferating activity, reducing power activity, alkylation activity. The HPLC analysis showed the absence of plumbagin peak observed in the HPLC chromatograms of both YKH aqueous and YKH ethanolic extracts. The YKH ethanolic extract yielded more chemical constituents than that of the YKH aqueous extract. The YKH aqueous extract was inactive against all cancer cells tested. Interestingly, YKH ethanolic extract caused cancer cell death in HCT116 colon cancer, HepG2 liver cancer, and Jurkat leukemic cancer cell lines in the concentration dependent manner. The following IC50 concentrations of the YKH ethanolic extract that possessed 50 % cell death after 24 h exposure in HCT116, HepG2, and Jurkat cell line were 195.4 ± 12, 171.7 ± 8.7, and 48.8 ± 5.7 µg/mL, respectively. Both aqueous and ethanolic extracts of YKH showed high antioxidant activity based on reducing power activity but did not have alkylation activity. At high concentration (250 µg/mL), YKH ethanolic extract can inhibit immune cells proliferation activity more than the YKH aqueous extract. An unexpected but critical outcome of our studies was the finding that anticancer activity is promised by selecting the plant extraction solvent with less polarity. Potential anticancer constituents were extracted from YKH using ethanol and these constituents cannot be found in aqueous solution of YKH.

Synthesis and Cytotoxic Evaluation of 2-Pyrazoline Derivative on Leukemia Cancer Cell Line K562

The 2-pyrazoline derivatives have a wide range of biological effects, such as anti-viral, anti-bacterial, anti-fungal, anti-depressant and anti-cancer effects. Studies have shown that compounds containing 2-pyrazoline along with another heterocycles may show more effective biological properties. In this study, a 2-pyrazoline derivative with a spiro-indenoquinoxaline ring at C3 position was synthesized by one-pot microwave-assisted method and its chemical structure was confirmed by 1H NMR spectroscopy. The cytotoxic effects of the compound were evaluated on the K562 cell line and phytohemagglutinin-activated peripheral blood mononuclear cells (PHA+PBMC) by MTT assay. Additionally, the cytotoxic effects of cisplatin on these cells were investigated and compared with those of 2-pyrazoline. The IC50 values ​​obtained from the 2-pyrazoline derivative effects on the K562 cell line and PHA+PBMC cells were 45 and 55 μg/mL respectively, while cisplatin inhibited proliferation of the same cells with IC50 value 1.71 and 7.8 µg/mL respectively. The results of this study showed that the synthesized derivative had a cytotoxic activity on the K562 cancer cell line at higher concentrations than cisplatin.

Essential oil extracted from leaf of Phoebe bournei (Hemsl.) yang: chemical constituents, antitumor, antibacterial, hypoglycemic activities

The essential oil were extracted from the leaf of Phoebe bournei (Hemsl.) Yang by a hydrothermal method and then analyzed by gas chromatography–mass spectrometry. The leaf oil mainly included α-copaene (5.44%), α-muurolene (7.32%), δ-cadinene (11.44%), 1s-calamenene (5.18%). Phoebe bournei (Hemsl.) Yang leaf essential oil had significant inhibitory activity against Epidermophyton floccosum and Microsporum gypseum, the potential antitumor activity towards leukemia, breast, and colon cancer cell lines was good. Phoebe bournei (Hemsl.) Yang leaf essential oil had weaker activity on the four tested bacteria, it exhibited a certain role in promoting glucose uptake by adipocytes.

Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Trimethoxy-ring Derivatives as BRD4 Inhibitors

Background: Bromodomain-containing protein 4 (BRD4) inhibitors synthesized with trimethoxy-ring refer to a new series of small molecular inhibitors. Currently, BRD4 offers the potential for research as a cancer therapeutic target. Based on previous studies, 17 trimethoxy-ring derivatives were designed as novel BRD4 inhibitors. Methods: All these new compounds were synthesized via the amide reaction. Their structures were identified by 1H NRM, 13C NRM spectra and HRMS. In vitro antitumor activities of the new compounds were evaluated by MTT. Molecular docking studies were conducted to explain the binding interactions of these compounds with BRD4 protein. Results: A series of novel trimethoxy-ring derivatives were synthesized as BRD4 inhibitors and screened by testing their inhibition against HCT116, MCF-7, K562 and KMS-1 cell lines. Most of the newly synthesized compounds exhibited moderate-to-good inhibitory activity against HCT116, MCF-7, and K562 cell lines, whereas some showed inhibitory activity against the KMS-1 cell line. Conclusion: Compound 3g demonstrated the most potent anti-tumor activity against breast (MCF-7), leukemia (K562), multiple myeloma (KMS-1), and colon cancer (HCT116) cell lines.

Novel quinoline derivatives carrying nitrones/oximes nitric oxide donors: Design, synthesis, antiproliferative and caspase-3 activation activities.

Novel quinoline derivatives carrying nitrones and oxime as nitric oxide donors were prepared and characterized using different spectroscopic techniques. Nitrones can release nitric oxide in larger amounts compared to corresponding oximes. Antiproliferative screening results showed that the 2-benzylthioquinoline nitrones 6e and 6f and the 2-methylthio analogues 6g and 6h exhibited promising antiproliferative activity especially against leukemia and colon cancer cell lines. Compounds 6c, 6e, and 6f exhibited higher potency as anticancer agents compared to doxorubicin, with IC50 ranging from 0.45 to 0.91 μM. A remarkable overexpression of caspase-3 protein levels was observed in cells treated with the tested compounds. Compound 6e exhibited more pre-G1 apoptosis and cell cycle arrest at the G2/M phase than in other phases. These results revealed that the tested compounds can cause programmed cell death through overexpression of caspase 3, which may be attributed to the release of nitric oxide.

Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety

Two series of cycloalkanespiro-5-hydantoins, namely cyclohexanespiro-5-hydantoins and cycloheptanespiro-5-hydantoins with a 4-substituted benzyl or a 2-(4-substituted phenyl)-2-oxoethyl group at N3 position, were synthesized and their effects on proliferation of human colon (HCT-116), leukemia (K562) and breast (MDA-MB-231) cancer cell lines were tested. For comparison, we also described the 5,5-diphenylhydantoin analogues. The structural features of the investigated compounds were characterized by elemental analysis, FT-IR, UV–Vis, 1H and 13C NMR spectroscopy and X-ray crystallography. Regarding their structure–activity relationships, it was shown that the substitution on the benzyl moiety with the methoxy, chloro or bromo group potentiated the antiproliferative activity relative to the parent compounds, while an increase in the size of the cycloalkyl group resulted mostly in a decrease of the antiproliferative activity. The single crystal X-ray analysis revealed the existence of dimers and chains formed by the NH⋯O hydrogen bonds. The analysis of the molecular descriptors of Lipinski demonstrated that all investigated compounds obeyed the rule of five. To further understand their geometry and electronic structure, DFT calculations with B3LYP method using 6-311++G(d,p) basic set were performed. In this context, the UV–Vis spectra of the investigated compounds were analyzed in detail, whereby the predicted absorption spectra from DFT calculation matched the experimentally obtained ones, with a good correlation. The interesting physico-chemical and pharmacologically relevant properties of the investigated compounds warrant their further investigation.