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Rosuvastatin (ROS), a statin drug with promising anticancer properties has a low bioavailability of approximately 20% due to lipophilicity and first-pass metabolism. This study aimed to enhance ROS anticancer efficacy through loading into flexible chitosomes. The chitosomes were prepared starting from negatively charged liposomes through electrostatic interactions with chitosan. The conversion of zeta potential from negative to positive confirmed the successful formation of chitosomes. The chitosan coating increased the particle size and zeta potential, which ranged from 202.0 ± 1.7 nm to 504.7 ± 25.0 nm and from - 44.9 ± 3.0 mV to 50.1 ± 2.6 mV, respectively. Chitosan and drug concentrations had an important influence on the chitosome properties. The optimum chitosome formulation was used to prepare ROS-loaded flexible chitosomes using different concentrations of four edge activators. The type and concentration of edge activator influenced the particle size, drug entrapment efficiency, and drug release rate of the flexible chitosomes. Flexible chitosomes significantly increased drug permeation through rat abdominal skin compared to control transferosomes and drug solution. The optimal ROS flexible chitosomes containing sodium deoxycholate as an edge activator had a 2.23-fold increase in ROS cytotoxic efficacy against MCF7 cells and a 1.84-fold increase against HepG2 cells. These results underscore the potential of flexible chitosomes for enhancing ROS anticancer efficacy., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: This study aimed to investigate the cytotoxic, apoptotic, invasion, metastasis, and heat shock proteins (HSPs) effects of N. sativa oil on breast and gastric cancer cells., Methods: We assessed the cytotoxic and apoptotic effects of various concentrations of N. sativa oil (10-50-100-200 µg/mL) on MCF7 breast cancer and AGS, an adenocarcinoma of the gastric cell line, at 24, 48 and 72 h using the MTT test. Additionally, the expression of the Caspase-3, BCL2/Bax, MMP2-9 and HSP60-70 gene was examined using RT-PCR in cell lines treating with N. sativa., Results: The MTT experiments demonstrate that N. sativa has a time and dose-dependent inhibitory effect on the proliferation of MCF7 and AGS cancer cells. The vitality rates of MCF7 and AGS cells treated with N. sativa were 77.04-67.50% at 24 h, 65.28-39.14% at 48 h, and 48.95-32.31% at 72 h. The doses of 100 and 200 µg/mL were shown to be the most effective on both cancer cells. RT-PCR analysis revealed that N. sativa oil extract increased caspase-3 levels in both cell lines at higher concentrations and suppressed BCL2/Bax levels. Exposure of MCF7 and AGS cell lines to N. sativa caused a significant decrease in the expression of MMP2-9 and HSP60-70 genes over time, particularly at a dosage of 200 µg/mL compared to the control group (p < 0.05)., Conclusions: Our findings indicate that N. sativa oil has a dose-dependent effect on cytotoxicity and the expression of apoptotic, heat shock proteins, and matrix metalloproteinases genes in breast and gastric cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Novel series of 2-oxindoline hydrazones 6a-h , 3-hydroxy-2-oxoindolines 9a-d and 2-oxoindolin-3-ylidenes 10a-d were prepared and assessed for their anticancer activity towards breast cancer cell line (MCF7). Compounds 6c , 6d , 6g , 9d , 10a and 10b (IC 50 = 14.0 ± 0.7, 15.6 ± 0.7, 13.8 ± 0.7, 4.9 ± 0.2, 6.0 ± 0.3 and 10.8 ± 0.5 µM, respectively) showed the highest growth inhibition activity against MCF7 when compared to staurosporine (IC 50 = 14.5 ± 0.7 µM). Cell cycle analysis exposed arrest at G1 phase for compounds 6c , 10 and 10b , at S phase for compounds 6d and 9d , and at G1/S phase for compound 6g . Apoptotic effect of compounds 6c , 6d , 6g , 9d , 10a and 10b was confirmed via their early and late apoptotic effects. A safety profile was revealed for compounds 6c , 6d , 6g , 9d , 10a and 10b on MCF10A treated normal cell. Also, compounds 6c and 10b displayed a promising CDK2 inhibition activity (IC 50 = 0.22 ± 0.01, 0.25 ± 0.01 µM, respectively). Also, docking study revealed comparable interactions with the native ligand (5-bromoindirubin). ADMET computational studies forecast the promising pharmacokinetic profile of the targeted compounds.Communicated by Ramaswamy H. Sarma.

Investigating novel, biologically-active coordination compounds that may be useful in the design of breast anticancer, antifungal, and antimicrobial agents is still the main challenge for chemists. In order to get closer to solving this problem, three new copper coordination compounds containing thiazole-based derivatives were synthesized. The structures of the synthesized compounds and their physicochemical characterization were evaluated based on elemental analysis, 1 H and l3 C nuclear magnetic resonance (NMR), flame atomic absorption spectroscopy (F-AAS), single-crystal X-ray diffraction, thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR). The pharmacokinetics were studied using SwissADME. The results obtained from the computational studies supported the results obtained from the MTT analysis, and the antimicrobial activity was expressed as the minimum inhibitory concentration (MIC).

Thiouracil and thiocytosine are important heterocyclic pharmacophores having pharmacological diversity. Antitumor and antiviral activity is commonly associated with thiouracil and thiocytosine derivatives, which are well known fragments for adenosine receptor affinity with many associated pharmacological properties. In this respect, 33 novel compounds have been synthesized in two groups: 24 thiouracil derivatives (4a-x) and 9 thiocytosine derivatives (5a-i). Antitumor activity of all the compounds was determined in the U87 MG glioblastoma cell line. Compound 5e showed an anti-proliferative IC 50 of 1.56 μM, which is slightly higher activity than cisplatin (1.67 μM). The 11 most active compounds showed no signficant binding to adenosine A 1 , A 2A or A 2B receptors at 1 μM. Brain tumors express high amounts of phosphodiesterases. Compounds were tested for PDE4 inhibition, and 5e and 5f showed the best potency (5e: 3.42 μM; 5f: 0.97 μM). Remakably, those compounds were also the most active against U87MG. However, the compounds lacked a cytotoxic effect on the HEK293 healthy cell line, which encourages further investigation., Competing Interests: Declaration of competing interest There is not any conflict of interest by the authors., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: Here we determined antitumour effects of purified compounds such as Valdecoxib, Rofecoxib, L-Methionine and Artocarpin against cancer cell lines., Methods: Using purified compounds, assays were performed to determine their effects against cancer cell lines using growth inhibition assays, cytotoxicity assays, and cell survival assays against HeLa, PC3 and MCF7 cells., Results: The results showed that the selected small molecules L-Methionine, Rofecoxib, and Artocarpin suppressed the growth of more than 90% PC3 cells at 40µM. Similarly, Valdecoxib alone and in combination with other molecules exhibited potent growth inhibition and cytotoxicity against cancer cells tested. Peptide from the serum of M. reticulatus, demonstrated selective cytotoxicity against cancer cells without inhibiting the growth of normal cells., Conclusion: These findings are significant and provide a basis for the rational development of therapeutic anticancer agents, however intensive research is needed to determine in vivo effects of the identified molecules together with their mode of action to realize these expectations. , .

Different 1,3,5-trisubstituted pyrazoline derivatives 2a-c, 3-c, 4a-f, 6a-c, 7a-f and 8a-d were prepared via condensation reaction of the appropriate chalcone 1a-c or 5a-c with various hydrazine derivatives. All compounds were screened for their cytotoxicity against breast MCF-7 cancer cell line and the normal fibroblasts WI-38. Thirteen compounds 2a, 3a, 3c, 4a-d, 6c, 7d, 7e, 8b, 8d and 8f revealed promising cytotoxicity against MCF-7 compared to the reference standard staurosporine and they were safe to the normal fibroblasts WI-38. In addition, compounds 3c, 6c, 7d, 8b and 8d elicited higher cytotoxicity than erlotinib and exhibited promising EGFR inhibitory activity at submicromolar level comparable to that of erlotinib except for compound 8b that may exert its cytotoxicity via another mechanism besides EGFR inhibition. Molecular docking of 3c, 6c, 7d, 8b and 8d in the active site of EGFR confirmed the obtained results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Accounting for mortality nearly one in four of human and second highest leading cause of death worldwide. Every year, about 10 million new cancers are diagnosed and causing major health issues in both developing and developed countries., Methods: A series of new dihydrazones were synthesized and screened for in vitro anticancer activity against three different MDA-MB-231, A546 and MCF7 cell lines and validated by DNA binding and molecular docking approaches., Result: In the present investigations, synthesized compounds 21, 22, 23 and 24 exhibited potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green comparing to Doxorubicin and ethidium bromide as a positive control respectively., Conclusion: The Structure Activity Relationship (SAR) showed that the electron withdrawing groups (-Cl, -NO2, - F, and -Br) favored the DNA binding studies and anticancer activity whereas, electron donating groups (-OH and - OCH3) showed moderate activity. In the molecular docking study, binding interactions of the most active compounds 21, 22, 23 and 24 stacked with A-T rich regions of the DNA minor groove by surface binding interactions were confirmed. Further, the tuning of active analogs for targeted therapy was warranted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A series of coumarin-tagged β-lactam triazole hybrids (10a-10o) were synthesized and tested for their cytotoxic activity against MDA-MB-231 (triple negative breast cancer), MCF-7 (estrogen receptor positive breast cancer (ER+)) and A549 (human lung carcinoma) cancer cell lines including one normal cell line, HEK-293 (human embryonic kidney). Two compounds 10b and 10d exhibited substantial cytotoxic effect against MCF-7 cancer cell lines with IC 50 values of 53.55 and 58.62 μm, respectively. More importantly, compounds 10b and 10d were non-cytotoxic against HEK-293 cell lines. Structure-activity relationship (SAR) studies suggested that the nitro and chloro group at the C-3 position of phenyl ring are favorable for anticancer activity, particularly against MCF-7 cell lines. Furthermore, antimicrobial evaluation of these compounds revealed modest inhibition of examined pathogenic strains with compounds 10c and 10i being the most promising antimicrobial agents against Pseudomonas aeruginosa and Candida albicans, respectively., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Zinc oxide nanoparticles (ZnO-NPs) are multifunctional oxide metal nanoparticles that have been considered by many due to their unique properties including UV filtration, semiconducting, antimicrobial, antifungal, and photocatalytic activity. In the present study, ZnO-NPs have been synthesized from Zn(SO 4 )·7H 2 O through the use of "green synthesis" method that utilizes Prosopis farcta aqueous extract. The characterization of synthesized ZnO-NPs have been performed by UV-Vis absorption, Fourier-Transform Infrared spectroscopy (FT-IR), Raman, Powder X-ray Diffraction (PXRD), Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray analysis (EDX). Results have illustrated that the synthesized nanoparticles contain a hexagonal shape and sheet form with sizes of 40-80 nm. The antifungal activity of ZnO-NPs against Candida albicans has shown that the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were 128 and 256 μg/ml, respectively. The cytotoxicity activity of synthesized nanoparticles was tested on breast cancer cells (MCF7), while the IC 50 was calculated to be 90 μg/ml., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: A non-hazardous synthetic methodology has been developed for the preparation of compounds based on indolofuroquinoxaline framework. Lemon juice that is known to play the role of a biocatalyst in various organic reactions was used for this purpose., Method: A number of indolofuroquinoxaline derivatives were prepared via the lemon juice mediated condensation of methyl 2-(2-chloro-1H-indol-3-yl)-2-oxoacetate or its N-alkyl derivatives with 1,2- diamines under ultrasound irradiation. All the synthesized compounds were screened via an MTT assay for their potential anticancer properties in vitro using a number of cancer cell lines including MDA-MB 231, and MCF7, K562, Colo-205 and IMR-32 and the non-cancerous HEK293 cell line. Compounds 3a, 3b and 3c showed promising growth inhibition against K562, MDA-MB 231 and MCF7 cell lines but no significant effects on HEK293 cell line suggesting their selectivity towards cancer cells., Results and Conclusion: Moreover, according to their IC50 values, all these compounds appeared to be relatively more potent towards K562 cell line over MDA-MB 231 and MCF7 cell lines indicating their potential against leukemia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background/objectives: In the Middle East, people consume camel milk regularly as it is believed to improve immunity against diseases and decrease the risk for cancer. Recently, it was noted that most of the beneficial effects of milk come from their nanoparticles, especially exosomes. Herein, we evaluated the anticancer potential of camel milk and its exosomes on MCF7 breast cancer cells (in vitro and in vivo) and investigated the possible underlying molecular mechanism of action., Methods/results: Administration of camel milk (orally) and its exosomes (orally and by local injection) decreased breast tumor progression as evident by ( a) higher apoptosis (indicated by higher DNA fragmentation, caspase-3 activity, Bax gene expression, and lower Bcl2 gene expression), ( b) remarkable inhibition of oxidative stress (decrease in MDA levels and iNOS gene expression); ( c) induction of antioxidant status (increased activities of SOD, CAT, and GPX), ( d) notable reduction in expression of inflammation-( IL1b, NFκB), angiogenesis-( VEGF) and metastasis-( MMP9, ICAM1) related genes; and ( e) higher immune response (high number of CD + 4, CD + 8, NK1.1 T cells in spleen)., Conclusions: Overall, administration of camel milk-derived exosomes showed better anticancer effect, but less immune response, than treatment by camel milk. Moreover, local injection of exosomes led to better improvement than oral administration. These findings suggest that camel milk and its exosomes have anticancer effect possibly through induction of apoptosis and inhibition of oxidative stress, inflammation, angiogenesis and metastasis in the tumor microenvironment. Thus, camel milk and its exosomes could be used as an anticancer agent for cancer treatment.

There is a continuous rise in the rate of medicine consumption because of the development of drug resistance by microbial pathogens. In the last one decade, silver nanoparticles (AgNPs) have become a remarkable choice for the development of new drugs due to their excellent broad-spectrum antimicrobial activity. In the current piece of work, we have synthesized AgNPs from the root extract of Phoenix dactylifera to test their antimicrobial and anti-cancer potential. UV-visible spectra showed the surface plasmon resonance peak at 420 nm λ max corresponding to the formation of silver nanoparticles, FTIR spectra further confirmed the involvement of biological moieties in AgNPs synthesis. Moreover, XRD analysis showed the crystalline nature of AgNPs and predicted the crystallite size of 15 to 40 nm. Electron microscopy analyses confirmed their spherical shape. In addition, synthesized AgNPs was also found to control the growth of C. albicans and E. coli on solid nutrient medium with 20 and 22 mm zone of inhibition, respectively. The 100% potency at 40 μg/ml AgNPs concentration was observed against E. coli and C. albicans after 4 h and 48 h incubation respectively. Importantly, AgNPs were also found to decrease the cell viability of MCF7 cell lines in vitro with IC 50 values of 29.6 μg/ml and could act as a controlling agent of human breast cancer. Based on our results, we conclude that biologically synthesized AgNPs exhibited multifunctional properties and could be used against human cancer and other infectious diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study was focused on developing a drug carrier system composed of a polymer containing hydroxyapatite (HAp) shell and a magnetic core of iron oxide nanoparticles. Doxorubicin and/or curcumin were loaded into the carrier via a simple diffusion deposition approach, with encapsulation efficiencies (EE) for curcumin and doxorubicin of 93.03 ± 0.3% and 97.37 ± 0.12% respectively. The co-loading of curcumin and doxorubicin led to a total EE of 76.02 ± 0.48%. Release studies were carried out at pH 7.4 and 5.3, and revealed a greater extent of release at pH 5.3, showing the formulations to have potential applications in tumor microenvironments. Cytotoxicity assays, fluorescence imaging and flow cytometry demonstrated that the formulations could effectively inhibit the growth of MCF-7 (breast) and HEpG2 (liver) cancer cells, being more potent than the free drug molecules both in terms of dose and duration of action. Additionally, hemolysis tests and cytotoxicity evaluations determined the drug-loaded carriers to be non-toxic towards non-cancerous cells. These formulations thus have great potential in the development of new cancer therapeutics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The aim of this study was to synthesize selenium nanoparticles (SeNPs) using cell suspension and total cell protein of Acinetobacter sp. SW30 and optimize its synthesis by studying the influence of physiological and physicochemical parameters. Also, we aimed to compare its anticancer activity with that of chemically synthesized SeNPs in breast cancer cells. Cell suspension of Acinetobacter sp. SW30 was exposed to various physiological and physicochemical conditions in the presence of sodium selenite to study their effects on the synthesis and morphology of SeNPs. Breast cancer cells (4T1, MCF-7) and noncancer cells (NIH/3T3, HEK293) were exposed to different concentrations of SeNPs. The 18 h grown culture with 2.7×10 9 cfu/mL could synthesize amorphous nanospheres of size 78 nm at 1.5 mM and crystalline nanorods at above 2.0 mM Na 2 SeO 3 concentration. Polygonal-shaped SeNPs of average size 79 nm were obtained in the supernatant of 4 mg/mL of total cell protein of Acinetobacter sp. SW30. Chemical SeNPs showed more anticancer activity than SeNPs synthesized by Acinetobacter sp. SW30 (BSeNPs), but they were found to be toxic to noncancer cells also. However, BSeNPs were selective against breast cancer cells than chemical ones. Results suggest that BSeNPs are a good choice of selection as anticancer agents., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Pyrazole moiety represents an important category of heterocyclic compound in pharmaceutical and medicinal chemistry. The novel 1-aryl-3, 5-bis (het) aryl pyrazole derivatives were synthesized with complementary regioselectivity. The chemical structures were confirmed by IR, 1 H NMR, 13 C NMR, and mass spectral analysis. The chemical entities were screened in various cancer cell lines to assess their cell viability activity. Results showed that the compound 3-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl) pyridine (5d) possessed maximum cytotoxic effect against breast cancer and leukemic cells. The cytotoxicity was confirmed by live-dead cell assay and cell cycle analysis. Mitochondrial membrane potential, Annexin V-FITC staining, DNA fragmentation, Hoechst staining, and western blot assays revealed the ability of compound 5d to induce cell death by activating apoptosis in cancer cells. Thus, the present study demonstrates that compound 5d could be an attractive chemical entity for the development of small molecule inhibitors for treatment of leukemia and breast cancer.

Background: The thiazolidinedione (TZD) class of peroxisome proliferator-activated receptor gamma (PPAR-γ) ligands are known for their ability to induce adipocyte differentiation, to increase insulin sensitivity including anticancer properties. But, whether or not upstream events like MAPK activation or PPAR-γ signaling are involved or associated with this anticancer activity is not well understood in breast cancer cells. The role of MAPK and PPAR pathways during the pioglitazone (Pio) induced PPAR-γ independent anticancer activity in MCF7 cells has been focused here., Methods: The anticancer activity of Pio has been investigated in breast cancer cells in vitro. Anti-tumor effects were assessed by alamar blue assay, Western blot analysis, cell cycle analysis, and annexin V-FITC/PI binding assay by flow cytometry, Hoechst staining and luciferase assay., Results: The anticancer activity of Pio is found to be correlating with the up regulation of CDKIs (p21/p27) and down regulation of CDK-4. This study demonstrates that the induction of CDKIs by Pio is due to the sustained activation of MAPK. The Pio-mediated activation of MAPK is transmitted to activate ELK-1 and the related anti-proliferation is blocked by MEK inhibitor (PD-184352)., Conclusions: Pio suppresses the proliferation of MCF7 cells, at least partly by a PPAR-γ-independent mechanism involving the induction of p21 which in turn requires sustained activation of MAPK. These findings implicate the utility of Pio in the treatment of PPAR positive or negative human cancers and the development of a new class of compounds to enhance the effectiveness of Pio., (Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

The present study reported the synthesis of tetrahydrocarbazoles hybridized with dithioate derivatives. Three series were synthesized namely alkyl dithiocarbonates (4a-d), heterocyclic dithiocarbamates (6a-g) and dialkyl dithiocarbamate (7). The synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7) and the human colon tumor cell line (HCT116). Most of the synthesized compounds exploited potent antitumor activity, especially compound 6f [4-chlorophenylpiperazine derivative], which showed cytotoxic activity against MCF7 superior to doxorubicin with IC50 value of 7.24 nM/mL.

Downregulation of claudin 1, a critical tight junction protein, has been correlated with increased invasiveness in breast cancer. However, recent studies suggest that claudin 1 contributes to the progression of some molecular subtypes of breast cancer. In this study, claudin 1 promotes migration in luminal-like MCF7 human breast cancer cells and increases their sensitivity to tamoxifen, etoposide, and cisplatin. We also observed an inverse relationship between upregulation of claudin 1 and TGFβ. Collectively, our results suggest that claudin 1 has the potential to be used as a predictive marker for treatment efficacy for specific breast cancer patient subgroups.

Breast cancer is classified into three groups according to its expression of hormone/growth factor receptors: (i) estrogen receptor (ER) and progesterone receptor (PR)-positive; (ii) human epidermal growth factor receptor 2 (HER2)-positive; and (iii) ER, PR, and HER2-negative (triple-negative). A series of methoxy-substituted biisoquinoline compounds have been synthesized as a potential chemotherapeutic agent for the triple-negative breast cancers which are especially challenging to manage. Structure activity relationship study revealed that rigid 6,6'-dimethoxy biisoquinoline imidazolium compound (1c, DH20931) exhibited the significant growth inhibitory effects on both triple-positive and triple-negative human breast cancer cell lines with IC50 in the range of 0.3-3.9 μM. The 1c (DH20931) is more potent than structurally related noscapine for growth inhibition of MCF7 cell line (IC50=1.3 vs 57 μM) and MDA-MB231 cell line (IC50=3.9 vs 64 μM)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The current interest of the team has been focused on investigation of novel amides with potential cytotoxicity. The presented series of compounds was synthesized from selected steryl hemiesters and heteroaromatic amines. The synthetic protocol was designed in a simple and economic way, and divided into several general methodologies applicable to the compounds synthesized. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with tests on normal human fibroblasts. Most of the lanosterol-based compounds (3-5 and 7-10) showed medium to good cytotoxicity, while only two derivatives of cholesterol (18 and 19) showed medium cytotoxicity on human T-lymphoblastic leukemia cell line. The compounds 8 and 9 displayed the reasonable cytotoxicity among this series of amides, tested on the cell lines of T-lymphoblastic leukemia [14.5±0.4 μM (8) and 18.5±3.9 μM (9)], breast adenocarcinoma [19.5±2.1 μM (8) and 23.1±4.0 μM (9)] and cervical cancer [24.8±5.3 μM (8) and 29.1±4.7 μM (9)]. Only the compound 8 was adequately less active on normal human fibroblasts (40.4±11.1 μM)., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Breast cancer is a heterogeneous group of neoplasms predominantly originating in the terminal duct lobular units. It represents the leading cause of cancer death in women and the survival frequencies for patients at advanced stages of the disease remain low. New treatment options need to be researched to improve these rates. The anti-tumor ether lipid edelfosine (ET) is the prototype of a novel generation of promising anticancer drugs. However, it presents several drawbacks for its use in cancer therapy, including gastrointestinal and hemolytic toxicity and low oral bioavailability. To overcome these obstacles, ET was encapsulated in Precirol ATO 5 lipid nanoparticles (ET-LN), and its anti-tumor potential was in vitro tested in breast cancer. The formulated ET-LN were more effective in inhibiting cell proliferation and notably decreased cell viability, showing that the cytotoxic effect of ET was considerably enhanced when ET was encapsulated. In addition, ET and ET-LN were able to promote cell cycle arrest at G1 phase. Moreover, although both treatments provoked an apoptotic effect in a time-dependent manner, such anti-tumor effects were noticeably improved with ET-LN treatment. Therefore, our results indicate that encapsulating ET in LN played an essential role in improving the efficacy of the drug., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Methotrexate, a folic acid molecular alternative inhibiting dihydrofolate reductase (DHFR), is employed for the treatment of various types of tumors combined with aspirin; acetylsalicylic acid is a nonsteroidal anti-inflammatory drug (NSAID). The present study aimed to detect the combined effects of both medications on MCF7 cell line activity. The drug combinations of aspirin and methotrexate were tested for cytotoxicity against the breast cancer cell line MCF7 using the MTT assay. The results showed that methotrexate, aspirin, and combination drugs have potent cytotoxicity against MCF7 cells. The mean IC50 of the methotrexate-treated group was 155.7 µg/ml (range, 77.89 to 311µg/ml. However, the IC50 of the aspirin-treated group was 465 µg/ml (range, 243.3 to 888.6 µg/ml). The IC50 of combination drugs used in the CompuSyn Isobologram on MCF7 cell lines, the cytotoxicity of medications methotrexate, aspirin, and combination demonstrated a synergistic action, and combination drugs have potent cytotoxicity against MCF7 cell lines. In conclusion, the combination of methotrexate and aspirin has a potent anticancer effect. [ABSTRACT FROM AUTHOR]

According to data provided by the World Health Organization (WHO), a total of 2.3 million women across the globe received a diagnosis of breast cancer in the year 2020, and among these cases, 685,000 resulted in fatalities. As the incidence of breast cancer statistics continues to rise, it is imperative to explore new avenues in the ongoing battle against this disease. Therefore, a number of new indolyl-hydrazones were synthesized by reacting the ethyl 3-formyl-1H-indole-2-carboxylate 1 with thiosemicarbazide, semicarbazide.HCl, 4-nitrophenyl hydrazine, 2,4-dinitrophenyl hydrazine, and 4-amino-5-(1H-indol-2-yl)-1,2,4-triazole-3-thione to afford the new hit compounds, which were assigned chemical structures as thiosemicarbazone 3, bis(hydrazine derivative) 5, semicarbzone 6, Schiff base 8, and the corresponding hydrazones 10 and 12 by NMR, elemental analysis, and X-ray single-crystal analysis. The MTT assay was employed to investigate the compounds' cytotoxicity against breast cancer cells (MCF-7). Cytotoxicity results disclosed potent IC50 values against MCF-7, especially compounds 5, 8, and 12, with IC50 values of 2.73 ± 0.14, 4.38 ± 0.23, and 7.03 ± 0.37 μM, respectively, compared to staurosproine (IC50 = 8.32 ± 0.43 μM). Consequently, the activities of compounds 5, 8, and 12 in relation to cell migration were investigated using the wound-healing test. The findings revealed notable wound-healing efficacy, with respective percentages of wound closure measured at 48.8%, 60.7%, and 51.8%. The impact of the hit compounds on cell proliferation was assessed by examining their apoptosis-inducing properties. Intriguingly, compound 5 exhibited a significant enhancement in cell death within MCF-7 cells, registering a notable increase of 39.26% in comparison to the untreated control group, which demonstrated only 1.27% cell death. Furthermore, the mechanism of action of compound 5 was scrutinized through testing against kinase receptors. The results revealed significant kinase inhibition, particularly against PI3K-α, PI3K-β, PI3K-δ, CDK2, AKT-1, and EGFR, showcasing promising activity, compared to standard drugs targeting these receptors. In the conclusive phase, through in vivo assay, compound 5 demonstrated a substantial reduction in tumor volume, decreasing from 106 mm³ in the untreated control to 56.4 mm³. Moreover, it significantly attenuated tumor proliferation by 46.9%. In view of these findings, the identified leads exhibit promises for potential development into future medications for the treatment of breast cancer, as they effectively hinder both cell migration and proliferation. [ABSTRACT FROM AUTHOR]

The number of deaths due to malignant neoplasms is increasing year by year. For this reason, new ways of preventing them and supporting treatment are being sought. One of them is adding plant extracts to food to increase its antioxidant, anti-inflammatory and anti-cancerogenic activity. The aim of the study was to examine the effect of different wild-grown fruits (chokeberry, elderberry, hawthorn and sea-buckthorn) added to wheat-flour cookies on the proliferation of: (i) normal BJ lines (fibroblasts); (ii) tumor cells of the MCF-7 (breast cancer) and (iii) WM793 (melanoma) lines. Methanol-acetone extracts were prepared from previously baked wheat-flour cookies fortified with fruits in order to use them in the further part of the research to prepare mixtures with concentrations of 0.5 mg/mL; 1 mg/mL; 1.5 mg/mL; 2.5 mg/mL. The viability and cytotoxicity of normal and neoplastic cells was examined. It was observed that the WM793 melanoma tumor line appeared to be more susceptible to the action of the tested extracts with the addition of selected wild-grown fruits compared to MCF7 breast cancer cells. Moreover, the greatest significant effect on the inhibition of WM793 cells among extracts with a concentration of 2.5 mg/mL was proved in the case of sea-buckthorn (p < 0.05). In terms of the inhibition of the MCF7 line, the effect was proved only in the case of sea buckthorn (p < 0.05), while the viability of these neoplastic cells was at most affected by elderberry and chokeberry extracts (p < 0.05). [ABSTRACT FROM AUTHOR]

In this study, we compared the effects of terpinolene against the anti-cancer agent cisplatin on proliferation, apoptotic activity and intracellular ROS (reactive oxygen species) production in cancerous (MCF-7) and non-cancerous (HEK-293) cell lines. Cisplatin presented a strong growth-inhibitory effect on both MCF-7 (IC25: 18.77 µM) and HEK-293 (IC25: 15.03 µM) cell lines. The growth-inhibitory effect of terpinolene was found to be weaker than cisplatin (IC25: 291.18 µM for MCF-7 and 345.35 µM for HEK 293 cells). The expression levels of BAX (by 1.86-fold), cleaved-PARP (by 2.23-fold) and pro-caspase-8 (by 1.74-fold) proteins increased in response to terpinolene treatment in MCF-7 cells. Curiously, the increase in the expression levels of these apoptotic markers was less pronounced in terpinolene-treated non-cancerous HEK 293 cells. Terpinolene, promoted a higher rate of apoptotic and necrotic cell death on MCF-7 cells (apoptotic cells: 25.28 %; necrotic cells: 17.70 %) when compared with HEK-293 cell line (apoptotic cells: 15.47 %; necrotic cells: 9.42 %). Interestingly, terpinolene caused a marked increase (2.05-fold) in intracellular ROS production in MCF-7 cells while HEK-293 cells appeared to be resistant to terpinolene or cisplatin treatments. In conclusion, although terpinolene showed a weaker growth-inhibitory effect on MCF-7 cancer cells, it exhibited a better selectivity than cisplatin in inducing cell death and intracellular oxidative stress in MCF7 breast cancer cells. [ABSTRACT FROM AUTHOR]

• We developed a novel series of pyrido[2,1-b]quinazoline-6-carboxamide compounds (8a-t) designed specifically as RNA polymerase inhibitors. • Immunofluorescence analysis using the RPA 194 antibody revealed a significant decrease in RPA 194 expression. • Assessment of apoptosis-inducing activity confirmed that treatment with 8e led to apoptosis in up to 43 % of HepG2 cells. • Molecular docking studies further validated the effective interaction of derivatives 8e and 8l with a hexamer of the DNA double helix, showcasing favorable binding energies and modes. In the present study, a new series of quinazolin-4(3 H)-one based compounds was designed, synthesized, and biologically evaluated as potential anticancer. The 11-oxo-11 H -pyrido [2, 1-b] quinazoline-6-carboxylic acid 3a-c was synthesized as a precursor to prepare the pyridoquinazolinecarboxamides derivatives with different amines (7a-e). The molecular structures of these novel compounds were characterized through the analysis of various spectroscopic methods. Following that, the antiproliferative activity of synthesized compounds was evaluated against HepG2, MCF7, and HT-29 cancer cell lines. Compound 8e , with an IC50 of 2.07 µM, demonstrated higher potency than doxorubicin (IC 50 =2.15±0.021 µM) against HepG2 cancer cells, while the potency of 8l against HepG2 (liver cancer) was comparable to Dox. The effect of 8e and 8l on the destruction of Pol I subunit of RPA194 was evaluated; 8e and 8l exhibited a reduction in RPA 194 compared to the control. The 8e induces 43.1 % and 8l 37.6 % of HepG2 cell deaths, with doxorubicin being 52 %. Molecular modeling studies show the good binding free energies ranged from -8.32 to -11.7 kcal/mol with a hexamer of the DNA double helix. Accordingly, our findings imply that these derivatives serve as promising precursors for the design of potent anticancer agents. [ABSTRACT FROM AUTHOR]

Breast cancer resistance to chemotherapy necessitates novel combination therapeutic approaches. Linc-RoR is a long intergenic noncoding RNA that regulates stem cell differentiation and promotes metastasis and invasion in breast cancer. Herein, we report a dual delivery system employing polyamidoamine dendrimers to co-administer the natural compound curcumin and linc-RoR siRNA for breast cancer treatment. Polyamidoamine dendrimers efficiently encapsulated curcumin and formed complexes with linc-RoR siRNA at an optimal N/P ratio. In MCF-7 breast cancer cells, the dendriplexes were effectively internalized and the combination treatment synergistically enhanced cytotoxicity, arresting the cell cycle at the G1 phase and inducing apoptosis. Linc-RoR gene expression was also significantly downregulated. Individual treatments showed lower efficacy, indicating synergism between components. Mechanistic studies are warranted to define the molecular underpinnings of this synergistic interaction. Our findings suggest dual delivery of linc-RoR siRNA and curcumin via dendrimers merits further exploration as a personalized therapeutic approach for overcoming breast cancer resistance. • Developed a dual nanoparticle system to co-deliver linc-RoR siRNA and curcumin. • PAMAM dendrimers efficiently co-delivered RNAi and a small molecule drug. • Enhanced cytotoxicity, G1 cell cycle arrest, and apoptosis in MCF-7. • Downregulation of linc-RoR expression has anticancer activity. • Demonstrated synergistic anticancer activity between curcumin and linc-RoR siRNA. [ABSTRACT FROM AUTHOR]

Breast cancer represents the most common non-cutaneous cancer and the second disease leading to cancer death for women in the world. Anti-diabetic and NSAIDs drugs have become as potential chemo preventive agents. This study is attentive to investigate the impact of metformin as oral hypoglycemic drug on breast cancer call lines as well as the effect of NSAIDS namely aspirin and ketorolac separately and compared the outcome. In vitro method was used to investigate the influence of metformin, aspirin and ketorolac on human breast cancer cells lines MCF7 and HBL100 cell lines as normal breast tissue and both maintain with minimal essential media. The results showed 0.0025 g/ml of aspirin inhibits significantly viability of MCF7 cell line 14.3% compared with HBL100 cell line (represents normal breast tissue)91% viable cells. In metformin cell viability 48% in MCF7 cell line at 2 mg/ml in comparison with HBL100 cell line with same concentration to be 89% availability. In case of ketorolac is only effective at high concentration of 15mg/ml which clinically not applicable. The obtained results might be useful to treat and prevent reoccurrence breast cancer with women at high risk especially aspirin drug. [ABSTRACT FROM AUTHOR]

A series of novel asymmetrical mono-carbonyl analogs of curcumin (AMACs) were synthesized and evaluated for cytotoxic activity using BSLT and MTT assay against Vero, HeLa, and MCF7 cell lines. The structures of the synthesized compounds were confirmed by FTIR, ¹H-NMR, 13C-NMR, and mass spectral data. The results of the cytotoxicity evaluation showed that the synthesized compounds exhibited moderate to very high toxic activity in BSLT (LC50 value 29.80-1704.23 μM); most of the compound exhibited cytotoxic activity against HeLa cell lines, which is comparable to the activity of cisplatin (IC50 value 40.65-95.55 μM), and most of the compound tested against MCF7 cell lines exhibited moderate to very high cytotoxic activity (IC50 value 7.86-35.88 μM). However, the selectivity index (SI) of the compounds was low (<1-1.96). Among the synthesized compounds, compound 1b was the most cytotoxic and selective against MCF7 cell lines. It could be considered for further development to obtain the more active and selective chemotherapeutic agents against breast cancer. [ABSTRACT FROM AUTHOR]

The study was caried out with the intention to bring out the biological prospective nature of the marine halophyte Salicornia europaea L. The bioactive phytochemicals of the halophyte were extracted. The chemicals in the crude extract were evaluated for cytotoxic activity against MCF7 cell line by MTT assay. The marine halophyte a was collected, washed and chopped into 5cm long parts and shade dried for 20 - 25 days in a dark room. The dehydrated and bleached plant material was subjected to Soxhlet extraction. Two solvents, viz methanol and ethyl acetate, were used to prepare decoction. The extracts were dried using rotary vacuum evaporator. chemical screening by GC-MS unveiled the presence of 32 compounds in ethyl acetate and 29 in methanol. The 3D structures of the phytochemicals were retrieved from Pub Chem. cytotoxic study showed promising results. The IC50 values of the individual extracts were evaluated and ethyl acetate extract exhibit minimum IC50 value and it was estimated to be 97.9µg/mL wereas methanol extract exhibit a minimum IC50 value of 117.1µg/mL. Hence, the study concludes that S. europaea L. provides a promising source of lead compounds that could be exploited in near future to treat cancer. [ABSTRACT FROM AUTHOR]

A novel series of 2-thiouracil sulfonamide derivatives (3 - 13) were synthesized; and their chemical structures were confirmed by spectral and elemental analyses. All compounds were tested for anticancer activity by SRB assay method against Breast (MCF7) and Colon (CaCo-2) cell lines. Most of the tested compounds are active against two cell lines in comparison to 5-fluorouracil. Compound 9 was the most potent against CaCo-2 and MCF7 cell lines (IC50=2.82 and 2.92 ìg/mL, respectively). Molecular docking studies for the best active compounds were performed on the active site of c-kit protein tyrosine kinase (PTK). All of the docked compounds exhibited proper fitting on the active site of the c-kit tyrosine kinas with fitness score range from 65.13±0.17 to 69.55±0.39 KJ/mol. The most active compound 9 showed high fitness score (69.55±0.39 KJ/mol). [ABSTRACT FROM AUTHOR]

Plants are among the major sources of biologically active substances possessing remarkable therapeutic values for treatment of various diseases, including cancer. Bulgarian flora includes about 770 medicinal plants species, 200 of which are sources for herbal drugs with application in medicine, cosmetics and food industry. Cotinus coggygria Scop. is a medicinal plant widely used in traditional phytotherapy with a variety of valuable biological properties. Currently, the plant is an object of intensive studies for assessment of its pharmacological capacity against different diseases. The objective of the present research was to evaluate the antitumor cytotoxic potential of Cotinus coggygria leaf aqueous ethanolic extract against human breast cancer cell line MCF7. The investigation of cancer cell viability inhibitory effect was performed by the MTT assay after treatment for 24 h with the extract at concentrations ranging from 5 μg/ml to 400 μg/ml. Light microscopy observations were performed to explore changes in cell morphology upon treatment. The obtained results revealed significant though not dosedependent cytotoxic activity of the extract with a detected value for the half maximal inhibitory concentration (IC50) of 40.6 μg/ml. The kinetics of the antitumor activity was followed after extract exposure for 24, 48 and 72 h with the IC50 concentration. The inhibitory effect decreased with time showing no linear time-dependency. In the present study, we report novel data on the in vitro antitumor cytotoxic activity of the Bulgarian herb Cotinus coggygria delegating it high antineoplastic potential. [ABSTRACT FROM AUTHOR]

The aim of this study was to synthesize several 16-dehydropregnenolone derivatives containing an imidazole ring at C-21 and a different ester moiety at C-3 as inhibitors of 5α-reductase 1 and 2 isoenzymes. Their binding capacity to the androgen receptor (AR) was also studied. Additionally, we evaluated their pharmacological effect in a castrated hamster model and their cytotoxic activity on a panel of cancer cells (PC-3, MCF7, SK-LU-1). The results showed that only the derivatives with an alicyclic ester at C-3 showed 5α-R2 enzyme inhibition activity, the most potent of them being 21-(1 H -imidazol-1-yl)-20-oxopregna-5,16-dien-3β-yl-cyclohexanecarboxylate with an IC 50 of 29 nM. This is important because prostatic benign hyperplasia is directly associated with the presence of 5α-R2. However, all the derivatives failed to inhibit 5α-R1 or bind to the AR. These alicyclic ester derivatives decreased the weight and size of androgen-dependent glands in the hamster, indicating they are very active in vivo and are not toxic. In addition, the 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3β-yl-acetate derivative showed the highest cytotoxic activity on the three cancer cell lines studied. It is therefore important in the synthesis of steroidal compounds to consider the size of the ester moiety at C-3 of the steroid skeleton, which is key in obtaining biological activity, as observed in this experiment. [ABSTRACT FROM AUTHOR]

The present work describes sustainable, catalyst free and bio-oriented multicomponent synthesis of 2-amino-3-cynospiro (5H-indeno[1,2- b ]pyran-4,3′-indoline)-2′5,-dione using isatin, malononitrile and 1,3-indandione. This study provides a facile synthesis of indeno-spiro compounds and is further supported with molecular docking, physico-chemical parameter and cytotoxicity study. The synthesized compounds were screened against breast carcinoma cell lines (MCF7, MDA-MB-435) and normal Vero monkey cell lines. Among all the tested compounds, the bromo- and chloro- substituted indeno-fused spirooxindole derivatives (entry B and D) were found to show selective potency against the MDA-MB-435 cancer cell lines exhibiting GI 50 value of 1.8 and 2.1 µM respectively. The selected compounds were also screened against the normal Vero monkey cell line, which showed good to excellent selectivity against inhibition of cancer cells. Furthermore, the in vitro confocal microscopy cell imaging of selected compounds showed cellular shrinkage and apoptosis in the cancer cells suggesting that the indeno-fused spirooxindoles can be explored as selective estrogen negative receptors with a safety profile. [ABSTRACT FROM AUTHOR]

• Synthesis of hydroxyindenopyrazolones was carried out in good yields. • The structures were confirmed by spectral (IR, 1H and 13CNMR, HRMS) and physical data. • Single crystal X-Ray crystallography of 3f was also performed. • Anticancer activity of hydroxyindenopyrazoles 3a‒o were assayed. A series of 1,8 b -dihydroindeno[1,2- c ]pyrazol-4(3a H)-one s has been efficiently synthesized on reaction of 2-(3-substitutedbenzoyl)-(1 H)-indene-1,3(2 H)-diones 1 and 2-hydrazinylbenzo[ d ]thiazole/2-hydrazinyl-6-substitutedbenzo[ d ]thiazoles 2 in presence of dry ethanol under reflux conditions in good yields. The structures of all the synthesized derivatives were elucidated by using different physical and spectral techniques (FTIR, 1H NMR, 13C NMR, 2D NMR and HRMS). The synthesized hydroxypyrazolones were assayed for their anticancer activity against two human cancer cell lines (i) lung carcinoma (A549) and (ii) breast carcinoma (MCF7) using MTT assay. Among all the tested compounds, 3d and 3k with IC 50 values in the range of 30.68 ± 0.57 µM to 34.87 ± 0.76 µM exhibited moderate inhibitory ability against both the tested cancer cell lines in comparison to the standard drug Doxorubicin (0.95 ± 0.10 µM for A549 and 1.09 ± 0.11 µM for MCF7). The moderately active compounds of the series i.e. 3d and 3k were further tested against normal human embryonic kidney cell line (HEK 293T) to examine their toxicity against normal cell lines. Selectivity Index (S.I.) of the most active compounds 3d and 3k was calculated for both the cancer cell lines which revealed that these derivatives i.e. 3d (S.I = 2.82 for A549 and 2.90 for MCF7) and 3k (S.I = 2.78 for A549 and 2.95 for MCF7) are safer anticancer agents. [Display omitted] [ABSTRACT FROM AUTHOR]

Gloriosa superba L. is commonly being called as glory lily. This perennial climber is designated as the State flower of Tamilnadu. It is extensively cultivated for colcichine, an alkaloid obtained from the seed being exploited for its medicinal properties. The present investigation on this climber was started with an intention to bring out the biomedical potentials with special reference to its anticancer properties. The plant was extracted with methanol and ethyl acetate using Soxhlet extraction unit and the extract was concentrated using vacuum rotavapor. The presence of 15 different compounds in methanol fraction and 1 compound in ethyl acetate fraction were determined by GC-MS. Extensive literature survey suggested that few records was available on anticancer properties of Gloriosa superba L. Hence, an attempt was made to evaluate its anticancer potentials The IC50 value of the compound against MCF7 cell line was found to be 84.23µg/mL. [ABSTRACT FROM AUTHOR]

A series of novel hexa-arm star shaped thiosemicarbazones with different substitutions at para positions emanating from cyclotriphosphazene core were prepared with excellent yields. The structure of all the synthesized compounds was confirmed by elemental analysis and spectroscopic methods (FT-IR, ¹H, 13C, 31P NMR, 2D HSQC and ESI-MS). The compounds were evaluated for their in vitro antiproliferative activity against breast cancer (MCF7) and ovarian cancer (PA-1) cell lines using MTT assay. The newly synthesized compounds exhibited moderate to good activity against the tested cell lines. Among them the halo substituted benzoic thiosemicarbazones were found to be more potent towards anticancer activity. [ABSTRACT FROM AUTHOR]

The present study was carried out to investigate cytotoxic activity of flower, leaf, stem and root extracts of five Artemisia species against breast cancer cell line (MCF7) and human embryonic kidney normal cell line (HEK293). The studied Artemisia species were A. absinthium, A. vulgaris, A. incana, A. fragrans and A. spicigera. The cytotoxic activity was measured by MTT assay at different concentrations (62.5, 125, 250, 500 μg/ml). Among these five species, methanol extracts of flower, leaf, stem and root of A. absinthium and A. vulgaris exhibited considerable cytotoxic activity. The flower extracts of these two species were found to have higher cytotoxic effect on MCF7 cell with an IC50 value of 221.5 and >500 μg/ml, respectively. Leaf methanol extract of A. incana also showed cytotoxic activity. Cytotoxic activity of different extracts of A. absinthium, A. vulgaris and A. incana against MCF7 was 10%-40% more than HEK293 cells. Not only the extracts of A. spicigera andA. fragrans did not show any cytotoxic effect against both cell lines, but also increased the number of cells. This study revealed that A. absinthium and A. vulgaris may have a great potential to explore new anticancer drugs. [ABSTRACT FROM AUTHOR]

3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d][1,3]oxazin-4-one (3) was prepared by hydrolysis of ethyl 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxylate (1) to afford the corresponding carboxylic acid 2, which was reacted with acetic anhydride to give 3. The pyrazolo[3,4-d][1,3]oxazin-4-one 3 was reacted with hydroxylamine hydrochloride, urea, thiourea, thiosemicarbazide, phenylhydrazine and aromatic amines to afford the corresponding pyrazolo[3,4-d]pyrimidin-4-ones 4, 5a,b, 6, 7, 8a-e, respectively. Condensation of pyrazoloxazine derivative 3 with 99% hydrazine hydrate afforded the 5-aminopyrazolo[3,4-d] pyrimidine derivative 9. Coupling of 9 with aromatic aldehydes yielded a series of 3,6-dimethyl-5-(4-substitutedbenzylideneamino)-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin- 4-ones 10a-e. The new compounds were tested for their antitumor activity on the MCF-7 human breast adenocarcinoma cell line. Almost all the tested compounds revealed antitumor activity, especially 3,6-dimethyl-5-(4-nitrobenzylideneamino)-1-phenyl-1,5- dihydropyrazolo[3,4-d]pyrimidin-4-one (10e) which displayed the most potent inhibitory activity with a half maximal inhibitory concentration (IC50) of 11 μM. [ABSTRACT FROM AUTHOR]

A few favanones were synthesised by cyclisation of corresponding 3-(heteroaryl)-1(2-hydroxyphenyl) prop-2-en-1-one with sodium acetate in alcohol--water and evaluated for activity. Synthesised compounds were assayed for their in vitro anticancer activity against three human cancer cell lines, mammary adenocarcinoma (MCF7), human colon adenocarcinoma (HT29) and human kidney adenocarcinoma (A498) using sulforhodamine B dye. Results indicated that most of the compounds exhibited signifcant in vitro anticancer potential. Among them, compound having furan ring showed most potent activity against all the tested cell lines. [ABSTRACT FROM AUTHOR]

Aim: This study aimed at production, extraction, purification and characterization of active antitumor compound from marine actinomycete secondary metabolites crude extract that was selected as most potent crude secondary metabolites from the preliminary screening of total fifty one extract. Material and methods: These tumor cell lines were breast cancer (MCF-7) (ATCC HTB-22) and Hepato-cellular carcinoma (HepG2) (ATCC 77400), colon cancer (Caco) (ATCC HTB-37) and cervix carcinoma (HeLa) (ATCC CRL-13011) cells. Purification process was done using silica gel column chromatography while purity was detected using thin layer chromatography (TLC). The active fraction was detected using morphological changes (cytotoxicity) by microscopic examination and anti-proliferative activity using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Result: The result indicated that there is only one fraction responsible for antitumor activity. This active fraction has cytotoxic and anti-proliferative activity against HepG2, MCF7, Caco and HELA cells with IC50=24.5, 20.1, 27.6 and 17.7µg/ml respectively. The analysis of physico-chemical, elemental and spectroscopic analysis (UV, IR, H.NMR, Mass spectroscopy) indicated that; the active compound has the nature of anthracycline compound. Conclusion: This purified compound has promising broad spectrum cytotoxicity and anti-proliferative activity in an in vitro system. The next research step shall include different optimization parameter that maximize productivity with long-term goal; discovery of an antitumor drug from actinomycetes native to Egyptian hot springshabitat. [ABSTRACT FROM AUTHOR]

Abstract: A series of new 1-aryl-4-benzylidenehydrazinyl-3-methylsulphanyl-pyrazolo[3,4-d]pyrimidines 6a–p was synthesized. The cytotoxic activity of the newly synthesized compounds against human breast cancer cell line, MCF7 was investigated. Most of the test compounds showed potent antitumor activity comparable to that of doxorubicin. The 1-phenyl series (6a–i) exhibited better antitumor activity than 1-(4-methoxyphenyl) series (6j–p). 4-[2-(4-Fluorobenzylidene)hydrazinyl]-3-(methylsulphanyl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine (6d) was the most active compound in this study with IC50 equal to 7.5 nM. [Copyright &y& Elsevier]

Context: Currently, natural products have been shown to present interesting biological and pharmacological activities and are used as chemotherapeutic agents. Plants have historically been used in treating cancer and are recognized for their ability to produce secondary metabolites. Juglans regia L. (Juglandaceae) has medicinal applications to treat a wide range of diseases such as cancer. Objective: The current study was designed to evaluate the antiproliferative activity of total extract as well as several fractions from the leaves of J. regia.The total phenolics, flavonoids, and condensed tannins content of these extracts were also determined to obtain further information on the correlation between the contents of phenolic compounds and antiproliferative effects as well as the leaf developmental stages. Materials and methods: Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry methods against human oral cancer, breast adenocarcinoma and colon adenocarcinoma cell lines. The total phenolics, flavonoids, and condensed tannins were determined by Folin-Ciocalteu, aluminum chloride and butanol-HCl colorimetric methods. Results: Our present study has shown that chloroform fraction has the lowest IC50 values (0.36-0.81 mg/mL) and also induces cell cycle arrest (G0\G1 phase) after a 24 h treatment. The colorimetric methods showed the highest amount of total phenolics, flavonoids, and condensed tannins in the methanol fraction (120.28 ± 2.32, 59.44 ± 0.87, 227.00 ± 4.91 mg/g of dry weight of extract). Discussion and conclusion: The results obtained herein indicate that walnut chloroform fraction may contain effective compounds which can be used as a chemotherapeutic agent. [ABSTRACT FROM AUTHOR]

Abstract: Celecoxib, an inhibitor of cyclooxygenase-2, is being investigated for enhancement of chemotherapy efficacy in cancer clinical trials. This study investigates the ability of cyclooxygenase-2 inhibitors to sensitize cells from different origins to several chemotherapeutic agents. The effect of the drug''s mechanism of action and sequence of administration are also investigated. The sensitivity, cell cycle, apoptosis and DNA damage of five different cancer cell lines (HeLa, HCT116, HepG2, MCF7 and U251) to 5-FU, cisplatin, doxorubicin and etoposide±celecoxib following different incubation schedules were analyzed. We found antagonism between celecoxib and the four drugs in the breast cancer cells MCF7 following all incubation schedules and between celecoxib and doxorubicin in all cell lines except for two combinations in HCT116 cells. Celecoxib with the other three drugs in the remaining four cell lines resulted in variable interactions. Mechanistic investigations revealed that celecoxib exerts different molecular effects in different cells. In some lines, it abrogates the drug-induced G2/M arrest enhancing pre-mature entry into mitosis with damaged DNA thus increasing apoptosis and resulting in synergism. In other cells, it enhances drug-induced G2/M arrest allowing time to repair drug-induced DNA damage before entry into mitosis and decreasing cell death resulting in antagonism. In some synergistic combinations, celecoxib-induced abrogation of G2/M arrest was not associated with apoptosis but permanent arrest in G1 phase. These results, if confirmed in-vivo, indicate that celecoxib is not a suitable chemosensitizer for breast cancer or with doxorubicin for other cancers. Moreover, combination of celecoxib with other drugs should be tailored to the tumor type, drug and administration schedule. [Copyright &y& Elsevier]

Abstract: A series of new pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines with different substituents at position 3 were synthesized. The effect of the newly synthesized compounds was tested in vitro on human breast adenocarcinoma cell line (MCF7). Some of the synthesized compounds exploited potent antitumor activity, especially the 3-amino derivative 12 which displayed the highest activity among the test compounds with IC50 equal to 3.74 μg/mL. [Copyright &y& Elsevier]

Abstract: Medicinal plants and culinary herbs have gained importance in the last decade as cytotoxic and antitumor agents. We hypothesized that some of the commonly used spices with reported antimicrobial activity might have antiproliferative activity. In the present study, selected spices used in Jordan were chemically analyzed and investigated for their antiproliferative activity to the adenocarcinoma of breast cell line (MCF7). The composition of the essential oils of Laurus nobilis L, Origanum syriacum L, Origanum vulgare L, and Salvia triloba L was analyzed by gas chromatography-mass spectrometry. The antiproliferative activities of the hydrodistilled volatile oils and the crude ethanol and water extracts were evaluated using the sulphorhodamine B assay. 1,8-Cineol was the major constituent in the hydrodistilled oils of both plants, L nobilis and S triloba, with concentrations of 40.91% and 45.16%, respectively. The major constituent of O syriacum was the carvacrol (47.10%), whereas that of O vulgare was trans-sabinene hydrate (27.19%). The ethanol crude extracts of O syriacum, L nobilis, and S triloba showed antiproliferative activity to MCF7 with IC50 values 6.40, 24.49, and 25.25 μg/mL, respectively. However, none of the hydrodistilled essential oils of the tested plant species or their aqueous extracts demonstrated cytotoxic activity. [Copyright &y& Elsevier]