Cyclodextrin Dispersion of Mebendazole and Flubendazole Improves In Vitro Antiproliferative Activity

Mebendazole and flubendazole are antihelmintic drugs that have re-entered the research spotlight due to their exhibited anticancer effects, thus making them strong candidates as repurposed drugs. However, these benzimidazole derivatives exhibit poor solubility in water and various organic solvents, which limits their bioavailability. With the aim of obtaining an improved drug solubility and increased biological effect, mebendazole and flubendazole were complexed with 2-hydroxypropyl-β-cyclodextrin (HPBCD). The binary 1:1 conjugates were physicochemically evaluated by X-ray diffraction, thermal analysis, and FTIR spectroscopy, revealing the formation of physical mixtures. The increased aqueous solubility of the binary 1:1 conjugates vs. pure benzimidazole compounds was demonstrated by performing dissolution tests. The in vitro antiproliferative activity of mebendazole and flubendazole, as well as their combination with HPBCD, was tested on two cancer cell lines, human melanoma—A375 and pulmonary adenocarcinoma—A549 by the MTT assay. The cytotoxic activity manifested in a dose-dependent manner while the presence of HPBCD increased the antiproliferative activity against the targeted cells. Treatment of A375 and A549 cell lines with the binary conjugates induced a significant inhibition of mitochondrial respiration, as revealed by high-resolution respirometry studies. Molecular docking analysis showed that one of the mechanisms related to MEB and FLU cytotoxic activity may be due to the inhibition of MEK/ERK proteins.

Download Full-text

Synthesis and Antiproliferative activity in vitro of Amidino Substituted 2-phenylbenzazoles

Croatica Chemica Acta ◽

10.5562/cca3531 ◽

2019 ◽

Vol 92 (2) ◽

pp. 181-189 ◽

Cited By ~ 2

Author(s):

Livio Racané ◽

Kristina Butković ◽

Irena Martin-Kleiner ◽

Marijeta Kralj ◽

Grace Karminski-Zamola ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Cancer Cell Lines ◽

Benzimidazole Derivatives ◽

Antiproliferative Agents ◽

Benzothiazole Derivatives

Within this work we describe the synthesis of versatile substituted 2-phenyl benzothiazole 3–10 and 2-phenylbenzimidazole 12–19 derivatives bearing amidino groups. Furthermore, the synthesized compounds were explored for their antiproliferative activity in vitro on three cancer cell lines. Tested compounds showed moderate to strong antiproliferative activity. Furthermore, the type of the attached amidino group on benzazole nuclei has the significant impact on the antiproliferative activity only within benzimidazole derivatives with 2-imidazolinyl substituted derivatives being more active in comparison to amidino substituted analogues. All obtained results revealed that this type of benzothiazole derivatives have a great potential for further optimization and development of more efficient potential antiproliferative agents.

Download Full-text

In vitro antiproliferative activity of some fluoro-substituted benzimidazole-based scaffolds

Biorganic and Medicinal Chemistry Reports ◽

10.25135/acg.bmcr.25.21.05.2065 ◽

2021 ◽

Vol 4 (1) ◽

pp. 10-17

Author(s):

Ronak Haj Ersan ◽

Nizami Duran

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Mtt Assay ◽

Antiproliferative Activity ◽

Cancer Cell Lines ◽

Positive Control ◽

Human Cells ◽

Benzimidazole Derivatives ◽

Antiproliferative Agents

In the present work, a series of fluoro-substituted benzimidazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Fluoro-substituted benzimidazole derivatives showed significant antiproliferative activity against all the tested cancer cell lines. All the derivatives were found to be less toxic as compared to methotrexate (positive control) in human cells, indicating selective and efficient antiproliferative activity of these benzimidazole derivatives. These findings suggest that compounds ORT14 and ORT15 among this series are most effective and have potential for detailed investigations.

Download Full-text

Apoptosis Inducing Effects of Thymus linearis Methanolic Extract in HCT-116 Cells and LC-MS Chemical Profiling of Its Active Constituents

The Natural Products Journal ◽

10.2174/2210315511999210128202816 ◽

2021 ◽

Vol 11 ◽

Author(s):

Rohina Bashir ◽

Ovais Zargar ◽

Qazi Parvaiz ◽

Rabia Hamid

Keyword(s):

Cell Lines ◽

Antiproliferative Activity ◽

Dna Cleavage ◽

Methanolic Extract ◽

Dependent Manner ◽

Regulation Of Expression ◽

Anti Cancer ◽

Hct 116 ◽

Hct 116 Cells

Background: Cancer is one of the major problems at present, to which vast research is being dedicated to find effective remedy. Medicinal plants are endowed with numerous molecules that could be effective in multiple diseases including cancer. Thymus linearis, being rich in phenols, terpenoid, and flavonoids have potential to provide anti-cancer entities. Methods: The extracts of Thymus linearis were investigated for in vitro anticancer activity using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay on a panel of cancer cell lines. The cellular and nuclear morphology was studied using microscopic techniques. Agarose gel electrophoresis was used for DNA fragmentation analysis. Protein expression was determined by western-blotting. LC-MS was used for phytochemical identification. Results: Among all the extracts, Thymus linearis methanolic (TLM) extract was found to exhibit antiproliferative activity on cell lines to varied degrees. TLM was found to be most potent against HCT-116 with an IC50 of 158μg/ml after 48hrs treatment, while being nontoxic to HEK-293 and FR-2 cells under similar concentrations. TLM decreased clonogenic potential of HCT-116 cells. It induced cell shrinkage, membrane blebbing and nuclear fragmentation characteristic of apoptotic in a dose dependent manner in HCT-116 cells. Prominent internucleosomal DNA cleavage was observed in HCT-116 cells after 48hrs TLM treatment. Western blot analysis revealed the up regulation of expression of Bax, caspases 9 and caspases 3 and downregulation of Bcl-2 proteins. The LC-MS data revealed the presence of Salvianolic acid H, Synparvolide C, Thymuside A and Jasmonic acid; 12-Hydroxy, O-β-D-glucopyranoside and polyphenolic flavonoids to which antiproliferative activity can be attributed. Conclusion: The results suggest that Thymus linearis methanolic extract could be valuable source of anti-cancer agents.

Download Full-text

Antiproliferative activity of synthesized some new benzimidazole carboxamidines against MCF-7 breast carcinoma cells

Zeitschrift für Naturforschung C ◽

10.1515/znc-2017-0067 ◽

2018 ◽

Vol 73 (3-4) ◽

pp. 137-145 ◽

Cited By ~ 2

Author(s):

Cigdem Karaaslan ◽

Filiz Bakar ◽

Hakan Goker

Keyword(s):

Breast Cancer ◽

Cytotoxic Activity ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Benzimidazole Derivatives ◽

Dependent Manner ◽

Base Pairs ◽

Mcf 7

AbstractBreast cancer is the most endemic cause of cancer among women in both developed and developing countries. Benzimidazole derivatives exemplify one of the chemical classes that show strong cytotoxic activity especially against breast cancer cells (MCF-7). Aromatic amidine derivatives are known as a group of DNA interactive compounds that bind minor groove of the genome, especially A-T base pairs, and show significant in vitro and in vivo toxicity toward cancer cells. In light of these studies, some new mono/dicationic amidino benzimidazole derivatives were synthesized and evaluated for cytotoxic activity on cultured MCF-7 breast cancer cells. Some of these compounds have strongly inhibited MCF-7 cell viability in a dose-dependent manner compared with clinically used reference compounds, imatinib mesylate and docetaxel. Among them, 4-[(5(6)-bromo-1H-benzimidazole-2-yl)amino]benzene-1-carboxamidine (30) showed the best inhibitory activity with IC50value of 4.6 nM.

Download Full-text

Pulsing with Blast Cell Lysate or Blast-Derived Total RNA Reverses the Dendritic Cell-Mediated Increase in Cytotoxic Activity of Cytokine-Induced Killer Cells Against Human Allogeneic Acute Myelogenous Leukemia Cells.

Blood ◽

10.1182/blood.v104.11.4531.4531 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4531-4531

Author(s):

Bjorn Schottker ◽

Angela Marten ◽

Carsten Ziske ◽

Marcus Gorschluter ◽

Ingo G.H. Schmidt-Wolf

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Acute Myelogenous Leukemia ◽

Blast Cell ◽

Myelogenous Leukemia ◽

Dependent Manner ◽

Total Rna ◽

Acute Myelogenous ◽

Cik Cell

Abstract Immunotherapeutic strategies may be a treatment option in patients with refractory acute myelogenous leukemia (AML) or, in cases of complete remission after conventional therapy regimens, may help to reduce disease recurrence or delay time to progression. Because evidence suggests a key role of dendritic cells (DCs) in cancer immunotherapy, we examined cytokine induced killer (CIK) cell responses in vitro after coincubation with autologous peripheral blood monocyte-derived DCs against three cell lines and allogeneic blasts from three patients with de novo AML. Although DCs were unable to enhance CIK cell effects against all three cell lines tested, the cytotoxic activity against the AML cells of the patients increased after coculture with mature DCs, which was significant in two of three patients. However, neither prior pulsing of the DCs with blast cell lysates nor with leukaemic cell-derived total RNA further enhanced the lytic capacity of the CIK cells. On the contrary, pulsing reduced the cytotoxic activity of the effector cells in a concentration-dependent manner. Because this decrease of allogeneic cytotoxicity was observed, we conclude that monocyte-derived DCs may be useful in autologous or allogeneic vaccine strategies for the treatment of AML or in priming donor lymphocytes in vitro, but unfractionated antigens as pulsing agents may have inhibitory effects on T cell efficiency and their employment in immunotherapeutic strategies for AML seems questionable.

Download Full-text

Isolation, identification, and cytotoxicity evaluation of phytochemicals from chloroform extract of Spathodea campanulata

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-021-00205-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Anita Wagh ◽

Santosh Butle ◽

Dipak Raut

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Chloroform Extract ◽

Positive Control ◽

Human Leukemia ◽

Dependent Manner ◽

Isolation And Identification ◽

H Nmr ◽

Dose Dependent

Abstract Background Spathodea campanulata P. Beauv. known as the African tulip tree has potential medicinal properties that have been shown traditionally for the treatment of various ailments. The aim of the present study was isolation, identification, and evaluation of the cytotoxic activity of phytochemicals from the chloroform extract of S. campanulata. Result Three compounds were isolated by using column chromatography and preparative TLC from chloroform extract of leaves of S. campanulata. The structures of the isolated compounds were elucidated by using spectroscopic methods, including, FTIR, ESI-TOF MS, 1H NMR, and 13C NMR spectroscopy. In vitro cytotoxic activity of compounds was evaluated by using SRB assay against human leukemia cancer cell lines (HL-60). Results were expressed in IC50 values. Stigmasta-5,22-dien-3-ol, octadecenamide, and umbelliferone were isolated and identified from chloroform extract. The isolated compounds showed cytotoxicity with decreasing cell viability in a dose-dependent manner, but it was found low as compared to positive control, i.e., Adriamycin against HL-60 cell lines. Conclusion The results indicate that isolated compounds, i.e., stigmasta-5,22-dien-3-ol (44.12μg/ml), octadecenamide (35.65μg/ml), and umbelliferone (80.60μg/ml) showed antiproliferative activity, but it was low compared to positive control Adriamycin (10.09 μg/ml). Also, according to our knowledge, this study is the first report on the isolation and identification of octadecenamide and umbelliferone from the leaves of S. campanulata. Graphical abstract

Download Full-text

INVESTIGATION ON PHARMACOGNOSY OF KATHA POWDER AS WELL AS IT’S IN VITRO CYTOTOXIC ACTIVITY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2021.v14i1.39717 ◽

2021 ◽

pp. 133-140

Author(s):

PANKAJ SHARMA

Keyword(s):

Cell Viability ◽

Cytotoxic Activity ◽

Cell Lines ◽

Hepg2 Cells ◽

Trypan Blue ◽

Dependent Manner ◽

Colorimetric Assays ◽

Dose Dependent ◽

Mcf 7

Objective: The present study delves into the investigation of quantitative phytochemical in Katha powder, and it is in vitro cytotoxic activity. Methods: Coarsely dried chips of Acacia catechu heartwood were treated with a 10% hydro-alcoholic solution to obtain Katha as the final product. The powdered Katha was standardized through pharmacognostic parameters. Phytochemical investigations were carried out to screen polyphenols (tannins and flavonoids) of interest which later were confirmed by thin-layer chromatography. The cytotoxicity effect of Katha powder on MCF-7, A431, and HepG2 cells was characterized by the trypan blue dye exclusion and MTT colorimetric assays technique. Control assay was carried out for samples containing only the appropriate volumes of blank solutions and showed no effect on cell growth. Different cells were exposed to Katha powder for about 48 h and performed cytotoxicity assays. The effect of Katha powder against these cell lines concentration range 10–100 μg/ml showed a decrease in percent cell viability in a dose-dependent manner, as compared with that of the control when examined by the trypan blue exclusion assay technique and MTT colorimetric assays technique. Results: Quantitative phytochemical investigations were showed that Katha is rich in the content of polyphenols (tannins and flavonoids) and having good pharmacological potential. The effect of Katha powder against these cell lines concentration range 10–100 μg/ml showed a decrease in percent cell viability in a dose-dependent manner. Conclusion: So from this investigation it is to be suggested that the Katha powder is rich in the phenolic compound and shows a good anticancer effect against MCF-7, A431, and HepG2 cells.

Download Full-text

1'-methylspiro[indoline-3,4'-piperidine] Derivatives: Design, Synthesis, Molecular Docking and Anti-tumor Activity Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180817999201117150714 ◽

2020 ◽

Vol 17 ◽

Author(s):

Junjian Li ◽

Lianbao Ye ◽

Yuanyuan Wang ◽

Ying Liu ◽

Xiaobao Jin ◽

...

Keyword(s):

Molecular Docking ◽

Cell Lines ◽

Active Sites ◽

Biological Activities ◽

Significant Inhibition ◽

Alkaline Condition ◽

Discovery Studio ◽

Hela Cell Lines ◽

Antiproliferative Activities

Background: Spirocyclic indoline compounds widely exist in numerous natural products with good biological activities and some drug molecules in many aspects. In recent years, it has attracted extensive attention as potent anti-tumor agents in the fields of pharmacology and chemistry. Objective: In this study, we focused on designing and synthesizing a set of novel 1'-H-spiro[indole-3,4'-piperidine] derivatives, which were evaluated by preliminary bioactivity experiment in vitro and molecular docking. Method: The key intermediate 1'-methylspiro[indoline-3,4'-piperidine] (B4) reacted with benzenesulfonyl chloride with different substituents under alkaline condition to obtain its sulfonyl derivatives (B5-B10). We evaluated their antiproliferative activities against A549, BEL-7402 and HeLa cells by MTT assay. We performed the CDOCKER module in Discovery Studio 2.5.5 software for molecular modeling of compound B5, and investigated the binding of compound B5 with the target proteins from PDB database. Results: The results indicated that compounds B4-B10 exhibited good antiproliferative activities against the above three types of cells, in which compound B5 with chloride atom as electron-withdrawing substituent on a phenyl ring showed the highest potency against BEL-7402 cells (IC50=30.03±0.43 μg/mL). By binging of the prominent bioactive compound B5 to CDK, c-Met, EGFR protein crystals, The binding energy of B5 with these three types receptors are -44.3583 kcal/mol, - 38.3292 kcal/mol, -33.3653 kcal/mol respectively. Conclusion: Six 1'-methylspiro[indoline-3,4'-piperidine] derivatives were synthesized and evaluated against BEL-7402, A- 549, HeLa cell lines. Compound B5 showed significant inhibition on BEL-7402 cell lines. Molecular docking revealed that B5 showed good affinity by the good fitting between B5 and these three targets with amino acid residues in active sites which encourage us to conduct further evaluation such as the kinase experiment.

Download Full-text

Synthesis and Evaluation of the Antitumor Activity of Novel 1-(4-Substituted phenyl)-2-ethyl Imidazole Apoptosis Inducers In Vitro

Molecules ◽

10.3390/molecules25184293 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4293

Author(s):

Zhen-Wang Li ◽

Chun-Yan Zhong ◽

Xiao-Ran Wang ◽

Shi-Nian Li ◽

Chun-Yuan Pan ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Cells ◽

Antiproliferative Activity ◽

Antitumor Agent ◽

Positive Control ◽

Selectivity Index ◽

Time Dependent ◽

Potential Candidate ◽

Dependent Manner

Novel imidazole derivatives were designed, prepared, and evaluated in vitro for antitumor activity. The majority of the tested derivatives showed improved antiproliferative activity compared to the positive control drugs 5-FU and MTX. Among them, compound 4f exhibited outstanding antiproliferative activity against three cancer cell lines and was considerably more potent than both 5-FU and MTX. In particular, the selectivity index indicated that the tolerance of normal L-02 cells to 4f was 23–46-fold higher than that of tumor cells. This selectivity was significantly higher than that exhibited by the positive control drugs. Furthermore, compound 4f induced cell apoptosis by increasing the protein expression levels of Bax and decreasing those of Bcl-2 in a time-dependent manner. Therefore, 4f could be a potential candidate for the development of a novel antitumor agent.

Download Full-text

In Vitro Cytotoxic Effects of Secondary Metabolites Present in Sarcopoterium Spinosum L.

Applied Sciences ◽

10.3390/app11115300 ◽

2021 ◽

Vol 11 (11) ◽

pp. 5300

Author(s):

Jozef Hudec ◽

Jan Mojzis ◽

Marta Habanova ◽

Jorge A. Saraiva ◽

Pavel Hradil ◽

...

Keyword(s):

Mammary Gland ◽

Ethyl Acetate ◽

Cytotoxic Activity ◽

Cell Lines ◽

Benzalkonium Chloride ◽

Ethanol Extract ◽

Cytotoxic Activities ◽

Sarcopoterium Spinosum ◽

Mcf 7

Sarcopoterium spinosum (L.) is a medicinal plant traditionally used for the treatment of various diseases including cancer in the Near- and Middle East. The fractions and constituents of the ethanol extract of S. spinosum were screened for in vitro cytotoxic activities on Jurkat (acute T-lymphoblastic leukemia), HeLa (cervical adenocarcinoma), MCF-7 (mammary gland adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), and MDA-MB-231 (mammary gland adenocarcinoma) cell lines using the MTT (3-(dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The ethanol extract was subsequently re-extracted with ethyl acetate and in its sub-fraction obtained by column chromatography three compounds (stachydrine, benzalkonium chloride and rutine) were the first time identified by nuclear magnetic resonance (NMR) analyses. The most active subfraction showed cytotoxic activity against HeLa, MCF-7, and Caco-2 cell lines. The three compounds mentioned, as standards of high-performance liquid chromatography (HPLC) quality, were studied individually and in combination. Cytotoxic activity observed might be due to the presence of benzalkonium chloride and rutin. Benzalkonium chloride showed the strongest growth suppression effect against HeLa cells (IC50 8.10−7 M) and MCF-7 cells (IC50 5.10−6 M). The mixture of stachydrine and benzalkonium chloride allowed a synergistic cytotoxic effect against all tested cancer and normal cells to be obtained. Anti-cancer activity of the plant extract of S. spinosum remains under-investigated, so this research describes how the three major compounds identified in the ethyl acetate extract can exert a significant dose dependent in vitro cytotoxicity.

Download Full-text