New Analogs of Polyamine Toxins from Spiders and Wasps: Liquid Phase Fragment Synthesis and Evaluation of Antiproliferative Activity

Purpose : This study aimed to evaluate the possible cytotoxic activity of the essential oil of the Eugenia uniflora leaves on normal and tumoral human cells by colorimetric cell viability assay, based on the use of tetrazolium salt (XTT). Methods : To achieve the cytotoxicity it was used normal human lung fibroblast cell line GMO7492A and the evaluation of antiproliferative activity was performed on three tumor cell lines, as follows: human glioblastoma (MO59J), human cervical adenocarcinoma (HeLa) and human breast adenocarcinoma (MCF-7). For the determination of cytotoxic concentration to the normal line, 12 concentrations were evaluated being from 2.44 to 5000 µg/mL. In the evaluation of antiproliferative activity were tested 8 different concentrations of the extract (3.91 to 500 µg/mL). Results : The results in the normal line GM07492A showed that concentrations higher or equal to 39.1 µg/mL are significantly different of the negative control. In the evaluation of antiproliferative activity on tumor cell lines MO59J, HeLa and MCF-7 was observed that the concentration of 125 µg/mL showed a cytotoxic effect on these lines being significantly different from the negative control. The results from the evaluation of the antiproliferative activity in different tumor cell lines of E. uniflora oil was not selective for the tested cell types. Conclusion : E. uniflora oil did not show cytotoxic activity in concentrations lower than 39.1 µg/mL, however, the values found to IC 50 for tumor cells were superior, concluding that the oil has no selectivity for tumor cells tested.

The in vitro antiproliferative and antioxidant studies of the leaf extract and fractions of Conyza sumatrensis was investigated by applying the Sulforhodamine-B and 2, 2-diphenyl-1-picrylhydrazyl assays (DPPH-RSA) respectively. While the antiproliferative activity was carried out at 1-250 and 1-100 μg/ mL for the extract and fractions against breast (MCF-7) and lung (NCI-H460) cancer cell lines, the antioxidant study was conducted using DPPH at 31.25 -500 μg/ mL with the total phenolic and flavonoid contents calculated as well with reference to quercetin and gallic acid respectively. The extract and fractions were observed to elicit cytotoxic and growth inhibitory effects against breast (MCF-7) and lung cancer cell lines (NCI-H460) respectively. At 250 μg/mL, the extract of C. sumatrensis gave cytotoxicity of –1.76 ± 0.20 % against MCF-7 cell lines and inhibited growth of NCI-H460 at +94.40 ± 1.0 % respectively. While the chloroform fraction at 100 μg/mL gave -5.38 ± 0.33 % and 91 ± 1.61 % against MCF-7 and NCI-H460 cell lines, the aqueous fraction was observed to be inactive. For the DPPH-RSA activity, the chloroform fraction demonstrated an IC50 value of 125.5 μg/ mL compare to quercetin at 62.5 μg/ mL. The bioactivities were more pronounced in the chloroform fraction. This work has shown that C. sumatrensis has antiproliferative and antioxidant activities which could be tied to the secondary metabolites present in the plant.

Novel 2,6-Bis(indolyl/ 5-bromoindolyl)dihydropyridine/pyridine hybrids as potential anti-tumor agents: Design, one-pot Green synthesis, molecular docking, and cytotoxicity evaluation.

Fumaria agraria (Fumariaceae) is an annual plant used traditionally in Algeria for various medicinal purposes. Alkaloids extracts from areal parts were subjected to solvent fractionation and GCMS analysis. Rates of alkaloids recorded were respectively of 700 mg/100 g of Dry Weight of total alkaloids “TA”, 400 mg/100 g DWof neutral fraction “NF”, 40 mg/100 g DW of acid fraction “AF” and 250 mg/100 g DWof the basic fraction “BF”. Protopine was found to be the most potent alkaloid of the total extract (41.55%). Fractionation showed that Protopine was found essentially in the BF fraction (60.7%). Antiproliferative activities of total alkaloids extract and BF fraction were assessed on MCF-7 and MDAMB- 231 breast cancer and MCF10A mammary normal cell lines, by trypan blue exclusion essay. Both TA extract and BF fraction showed potent antiproliferative activities against MCF-7 breast cancer cells in varying degrees with respective IC50 of 47.8 ± 1.8 µg/ml and 17.6 ± 0.4 µM, without cell death induction but no impact was observed on normal MCF-10A cell growth. MCF7 Cell line was most sensitive (IC50 of 17,6 ± 0,4µM) to BF fraction effect than MDAMB-231 one (IC50 of 36,4 ± 0,6µM). Isoquinolein alkaloids of Fumaria agraria and specially the fraction which contain Protopine showed potent antiproliferative activity against breast cancer cells.

Synthesis and anticancer activity evaluation of novel azacalix[2]arene[2]pyrimidines

Exploration of anticancer potency of N(4) thiomorpholinyl isatin/5-haloisatin thiosemicarbazones on coordination to Cu2+ ion

Anticancer agents based on Plastoquinone analogs with N-phenylpiperazine: Structure-activity relationship and mechanism of action in breast cancer cells

Diastereomeric and geometric analogs of calcipotriol, PRI-2202 and PRI-2205, were synthesized as advanced intermediates from vitamin D C-22 benzothiazoyl sulfones and side-chain aldehydes using our convergent strategy. Calcitriol, calcipotriol (PRI-2201) and tacalcitol (PRI-2191) were used as the reference compounds. Among a series of tested analogs the diastereomeric analog PRI-2202 showed the strongest antiproliferative activity on the human breast cancer cell line MCF-7, whereas the geometric analog PRI-2205 was the weakest. Both analogs were less potent in antiproliferative activity against HL-60 cells compared to the reference compounds. The ability to potentiate antiproliferative effect of cisplatin or doxorubicin against HL-60 cells or that of tamoxifen against the MCF-7 cell line was observed at higher doses of PRI-2202 or PRI-2205 than those of the reference compounds. The proapoptotic activity of tamoxifen, expressed as the diminished mitochondrial membrane potential, as well as the increased phosphatidylserine expression, was partially attenuated by calcitriol, PRI-2191, PRI-2201 and PRI-2205. The treatment of the MCF-7 cells with tamoxifen alone resulted in an increase in VDR expression. Moreover, a further increase in VDR expression was observed when the analogs PRI-2201 or PRI-2205, but not PRI-2191, were used in combination with tamoxifen. This observation could partially explain the potentiation of the antiproliferative effect of tamoxifen by vitamin D analogs.

Thesis Abstract Background: Although anticancer treatment with chemotherapy is effective, cancer response occurs due mainly to reduction of cancer stem cells. The development of cancer stem cell is regulated by several genes including NOTCH1, SIX1 and WNT1. Aim: we have found recently that treatment of Caco2, HepG2 and MCF-7 with Achillia santolina or Rahanus sativus results antitumor effect. In this study we aimed to evaluate the effect of these natural product on the gene expressions NOTCH1, SIX1 and WNT1 in Caco2 and MCF-7. Materials and Methods: Colon adenocarcinoma cell line (Caco2) and Breast cancer cell line (MCF-7) as well as normal amniotic cell line (WISH) were treated with 110 IC50 concentration of Achillea santolina and Raphanus sativus extracts to compared to 110 IC50 of cisplatin as a reference chemotherapy drug. Total RNA was extracted after 72 hours of treatment and incubation then cDNA was prepared for reverse transcriptase PCR for NOCH1, WNT1, and SIX1. Results: R. sativus treatment highly decreased NOTCH1 expression in MCF7 and Caco2 cell lines, while decreased SIX1 gene expression in Caco2 cell line and WNT1 in MCF7 cell line. On the other hand, A. santolina observably decreased the WNT1 gene expression in MCF7 cell line. Conclusion: The crude extracts of R. sativus decreased the developmental gene expression of NOTCH1, SIX1 in Caco2 cell line as same as on NOTCH1 and WNT1 in MCF-7 cell line more than cisplatin chemotherapy. While the A. santolina crude extract decrease the expression of WNT1 in MCF-7 cell line more than cisplatin chemotherapy.

A series of new imidazole substituted indeno[1,2-b]quinoline-9,11-dione derivatives were synthesized and evaluated for their antiproliferative effects on HeLa, LS180, MCF-7 and Jurkat human cancer cell lines. Antiproliferative effects were evaluated using MTT assay. Prepared compounds exhibited weak to good antiproliferative activity in evaluated cell lines. Prepared compounds were more potent in Jurkat cell line when compared to LS180, HeLa and MCF-7 cell lines. Compounds 29 (IC16 = 0.7 μM) and 31 (IC16 = 1.7 μM) and 33 (IC16 = 1.7 μM) were found to be the most potent molecules on Jurkat cell lines. Moreover; it was found that some of the tested compounds bearing imidazole-2-yl moiety on the C11-position of dihydropyridine ring exhibited superior antiproliferative activity in comparison to cis-platin especially in Jurkat cell line (compounds 29, 31, and 33). It seemed that the introduction of electron-withdrawing groups on the imidazole ring enhanced the antiproliferative potential of these compounds (compounds 27, 29 and 31). The results of this study proposed that some of the imidazole substituted indeno[1,2-b]quinoline-9,11-dione compounds may act as efficient anticancer agents in vitro, emphasizing their potential role as a source for rational design of potent antiproliferative agents.

Thiosemicarbazones and 4-thiazolidinones indole-based derivatives: Synthesis, evaluation of antiproliferative activity, cell death mechanisms and topoisomerase inhibition assay

The current study was performed to screen the extracts of Artemisia nilagirica (C.B. Clarke) Pamp. for antiproliferative and antiinflammatory properties. Antiproliferative activity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Antiinflammatory activity was evaluated in terms of lipoxygenase and xanthine oxidase inhibitory activities. Results indicated that out of the 3 extracts tested, methanol extract was found to inhibit Y79 (human retinoblastoma) and MCF-7 (human breast adenocarcinoma) cell lines. The same extract was also found to inhibit lipoxygenase and xanthine oxidase enzymes in a concentration-dependent manner with an IC50 of 128.20±3.39 and 144.23±2.04 μg/ml for lipoxygenase and xanthine oxidase, respectively. The present study highlighted the antiproliferative potential of the plant against cancer cell lines. The extracts inhibited lipoxygenase and xanthine oxidase enzymes. Therefore, this plant could be a valuable source for anticancer and antiinflammatory molecules.

An important role has been considered forthe vascular endothelial growth factor receptor 2 (VEGFR-2) in the angiogenesis process, so that its inhibition is an important scientific way for cancer treatment. In this work, new thienopyrimidine derivatives were synthesized and evaluated. Compared with sorafenib, the majority of the target compounds had antiproliferative activity against the PC3, HepG2, MCF7, SW480, and HUVEC cell lines, especially 9h with IC50 values of 4.5-15.1 μM, confirming the noticeable cytotoxic effects on the listed cell lines (PC3, HepG2, SW480, and HUVEC). Analyses by flow cytometry on SW480 and HUVEC cells revealed that 9n, 9k, 9h, and 9q led to apoptotic cell death. The result of the chick chorioallantoic membrane assay showed that 9h effectively reduced the number of corresponding blood vessels. Finally, the inhibitory effect on VEGFR-2 phosphorylation was considered as the outcome of Western blot analysis of compound 9h.

BackgroundA series of 2-amino-4-aryl-4H-benzo[h or f]chromene-3-carbonitrile derivatives were synthesized and evaluated for inhibition of Src kinase and cell proliferation in breast carcinoma (BT-20) cell lines.MethodsThe one-pot, three-component reaction of α or β-naphthol, malonitrile and an aromatic aldehyde in the presence of diammonium hydrogen phosphate was afforded the corresponding 2-amino-4-aryl-4H-benzo[h or f]chromene-3-carbonitrile derivatives, All target compounds were evaluated for inhibition of Src kinase and cell proliferation in breast carcinoma (BT-20) cell lines.ResultsAmong all tested compounds, unsubstituted 4-phenyl analog 4a showed Src kinas inhibitory effect with IC50 value of 28.1 μM and was the most potent compound in this series. In general, the compounds were moderately active against BT-20. 3-Nitro-phenyl 4e and 3-pyridinyl 4h derivatives inhibited the cell proliferation of BT-20 cells by 33% and 31.5%, respectively, and found to be more potent compared to doxorubicin (25% inhibition of cell growth).ConclusionThe data indicate that 4-aryl-4H-naphthopyrans scaffold has the potential to be optimized further for designing more potent Src kinase inhibitors and/or anticancer lead compounds.

Background: In many types of cancer, uncontrolled growth and proliferation of cells occur due to abnormalities in their genes, mutations of pro-apoptotic proteins, or upregulation of anti-apoptotic proteins. Triazolinedione and pyrrole derivatives are compounds with anti-microbial, anti-fungal, anti-inflammatory, and anti-cancer activities. Pyrrole and its derivatives are critical heterocycle compounds that are significant in anticancer studies and highly preferred in research. Objective: This study aimed to investigate the effects of dihydropyrrole derivatives substituted with triazolinedione on the MCF-7 (breast cancer) cell line’s apoptosis, ER stress, and heat shock genes. Methods: The mRNA levels of apoptosis, ER stress, and heat shock proteins were assessed by qRT-PCR method in the MCF-7 cell line. The investigation of ADMET features, crucial pharmacokinetic indices for the potential candidacy of compounds as drugs, has been meticulously designed. In silico-induced molecular docking studies were conducted to further explore the interaction and elucidate the orientation of hybrid compounds within the active sites of BCL-2, PARP, HSP70, HSP90, and GRP78. Results: It was determined that the compounds caused cell death by modulating apoptotic (compound IV), ER stress, and heat shock proteins (compounds XI and XVI) through up- and downregulation. Our findings have pointed to the effects of triazolinedione-substituted dihydropyrrole derivatives, exhibiting antitumor activity on apoptosis, ER stress, and heat shock genes in the MCF- 7 cell line. Conclusion: The compounds investigated in this study have been found to be promising for anticancer research.