S16020 pyridocarbazole derivatives display high activity to lung cancer cells

Background: Despite the dynamic development of medicine, globally cancer diseases remain the second leading cause of death. Therefore, there is a strong necessity to improve chemotherapy regimens and search for new anticancer agents. Pyridocarbazoles are compounds with confirmed antitumor properties based on multimodal mechanisms, i.a. DNA intercalation and topoisomerase II-DNA complex inhibition. One of them, S16020, displayed a wide spectrum of activity. Objective: The aim of the study was to investigate the antitumor potency of six S16020 derivatives, synthesized according to the SAR (structure-activity relationship) method. Methods: The biological evaluation included influence on cancer cell viability, proliferation, and migration, as well as P-glycoprotein activity. NHDF, A549, MCF-7, LoVo, and LoVo/DX cell lines were used in the study. Results: All derivatives displayed low toxicity to normal (NHDF) cells at 1 and 2 µM (≤ 20% of cell growth inhibition). The highest reduction in cell viability was noted in A549 cells which was accompanied by significant disruption of cells proliferation and motility. Compound 1 exhibited the strongest cytotoxic, antiproliferative, and antimigratory effects, higher than the reference olivacine. A significant reduction in P-glycoprotein activity was found for derivatives 6 and 1. Conclusion: S16020 derivatives could be considered as potential candidates for new anticancer drugs.

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DNA-Binding and Topoisomerase-I-Suppressing Activities of Novel Vanadium Compound Van-7

Bioinorganic Chemistry and Applications ◽

10.1155/2012/756374 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Xiao-mei Mo ◽

Zhan-fang Chen ◽

Xin Qi ◽

Yan-tuan Li ◽

Jing Li

Keyword(s):

Dna Binding ◽

Anticancer Agents ◽

Topoisomerase I ◽

A549 Cells ◽

Anticancer Activities ◽

Vanadium Compound ◽

New Class ◽

M Phase ◽

Low Toxicity ◽

Topo Ii

Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal anticancer agents in combination to its low toxicity. Here, we found a vanadium compound Van-7 as an inhibitor of Topo I other than Topo II using topoisomerase-mediated supercoiled DNA relaxation assay. Agarose gel electrophoresis and comet assay showed that Van-7 treatment did not produce cleavable complexes like HCPT, thereby suggesting that Topo I inhibition occurred upstream of the relegation step. Further studies revealed that Van-7 inhibited Topo I DNA binding involved in its intercalating DNA. Van-7 did not affect the catalytic activity of DNase I even up to100 μM. Van-7 significantly suppressed the growth of cancer cell lines with IC50at nanomolar concentrations and arrested cell cycle of A549 cells at G2/M phase. All these results indicate that Van-7 is a potential selective Topo I inhibitor with anticancer activities as a kind of Topo I suppressor, not Topo I poison.

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Bioactive Secondary Metabolites from Marine Streptomyces griseorubens f8: Isolation, Identification and Biological Activity Assay

Journal of Marine Science and Engineering ◽

10.3390/jmse9090978 ◽

2021 ◽

Vol 9 (9) ◽

pp. 978

Author(s):

Wenzhi Yang ◽

Guangjie Liang ◽

Yang Sun ◽

Zhijin Gong

Keyword(s):

Staphylococcus Aureus ◽

Anticancer Agents ◽

A549 Cells ◽

Klebsiella Aerogenes ◽

Proteus Vulgaris ◽

Invasion And Migration ◽

Bioactive Natural Products ◽

Streptomyces Griseorubens ◽

Marine Streptomyces ◽

And Migration

Marine actinomycetes are a potential source of a wide variety of bioactive natural products. Herein, four cyclic dipeptides, namely, cyclo(L-Val-L-Pro) (compound 1), cyclo(L-Pro-L-Leu) (compound 2), cyclo(L-Pro-L-Tyr) (compound 3) and cyclo(L-Pro-L-Phe) (compound 5), and an N-acetyltyramine (compound 4) were first isolated and identified as products of the marine Streptomyces griseorubens f8. Compounds 3 and 5 exhibit antibacterial activity against Staphylococcus aureus, Klebsiella aerogenes and Proteus vulgaris. The minimum inhibitory concentrations (MICs) against Staphylococcus aureus, Klebsiella aerogenes and Proteus vulgaris are 160 µg/mL, 100 µg/mL, 120 µg/mL for the compound 3 and 180 µg/mL, 130 µg/mL 150 µg/mL for the compound 5, respectively. In addition, compounds 1, 2, 3 and 5 was first found to have the ability to inhibit the invasion and migration of A549 cells (lung cancer cells), which exhibited the potentiality for these compounds to be used as novel anticancer drugs. This study provides a novel production strain for compounds 1, 2, 3 and 5, and four potential promising anticancer agents.

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Synthesis and Biological Evaluation of New 1,3,4-Oxadiazoles as Potential Anticancer Agents and Enzyme Inhibitors

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180322123327 ◽

2018 ◽

Vol 18 (6) ◽

pp. 914-921 ◽

Cited By ~ 1

Author(s):

Leyla Yurttaş ◽

Betül K. Çavuşoğlu ◽

Gülşen A. Çiftçi ◽

Halide E. Temel

Keyword(s):

Cell Line ◽

Cell Lines ◽

Anticancer Agents ◽

Enzyme Inhibitors ◽

A549 Cells ◽

Fibroblast Cell ◽

Biological Evaluation ◽

Rat Glioma ◽

Human Lung Carcinoma ◽

Nih 3T3

Background: 1,3,4-Oxadiazoles have been known with a wide variety of pharmacological activities including anticancer activity. Objective: In this study, novel 2,5-disubstituted 1,3,4-oxadiazole derivatives were synthesized and evaluated for determining their anticancer, anticholinesterase and lipoxygenase (LOX) inhibitory activity. Methods: All compounds were tested against C6 rat glioma, A549 human lung carcinoma and NIH/3T3 mouse embryo fibroblast cell lines to define cytotoxic concentrations and apoptosis induction levels which they cause. Results: Many of the compounds exhibited remarkable potency that compounds 2a, 2b, 2e, 2h and 2j against C6 cells and compounds 2a, 2b, 2d, 2g, 2i, 2j against A549 cells were found more active than cisplatin. Compound 2d namely, 2-[(5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl)thio]-1-(4-chlorophenyl)ethan-1-one induced apoptosis of A549 cells with 74.9% whereas cisplatin caused 70.9% percentage. Conclusion: Among them, compounds 2d and 2j against A549 cell line, compounds 2b and 2e against both tumor cell lines showed selective cytotoxicity evaluating the inhibition concentration against NIH/3T3 cell line. None of the compounds showed significant acetylcholinesterase (AChE) and lipoxygenase inhibitory activities.

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Newly Synthesized Imino-Derivatives Analogues of Resveratrol Exert Inhibitory Effects in Breast Tumor Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21207797 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7797

Author(s):

Domenico Iacopetta ◽

Rosamaria Lappano ◽

Annaluisa Mariconda ◽

Jessica Ceramella ◽

Maria Stefania Sinicropi ◽

...

Keyword(s):

Breast Cancer ◽

Anticancer Agents ◽

Breast Tumor ◽

Topoisomerase Ii ◽

Apoptotic Cell ◽

Beneficial Effects ◽

Small Series ◽

Low Toxicity ◽

Anti Tumor Activity

Breast cancer represents the most frequently diagnosed malignancy in women worldwide. Various therapeutics are currently used in order to halt the progression of breast tumor, even though certain side effects may limit the beneficial effects. In recent years, many efforts have been addressed to the usefulness of natural compounds as anticancer agents due to their low toxicity. Resveratrol, a stilbene found in grapes, berries, peanuts and soybeans, has raised a notable interest for its antioxidant, anti-inflammatory, and antitumor properties. Here, we report the design, the synthesis and the characterization of the anticancer activity of a small series of imino N-aryl-substituted compounds that are analogues of resveratrol. In particular, the most active compound, named 3, exhibited anti-tumor activity in diverse types of breast cancer cells through the inhibition of the human topoisomerase II and the induction of apoptotic cell death. Therefore, the abovementioned compound maybe considered as a promising agent in more comprehensive treatments of breast cancer.

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Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands

International Journal of Molecular Sciences ◽

10.3390/ijms22041711 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1711

Author(s):

Huang Zeng ◽

Shuangshuang Kang ◽

Yu Zhang ◽

Ke Liu ◽

Qian Yu ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Oleanolic Acid ◽

Anticancer Agents ◽

Biological Evaluation ◽

Vascular Endothelial ◽

G Quadruplex ◽

Selective Ligands ◽

And Migration ◽

Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is an angiogenic growth factor and plays a key role in tumor progression. The C-rich DNA sequence of VEGF promoter can form i-motif structure, which is a potential target for the development of novel anticancer agents. However, there is a limited number of chemotypes as the selective ligands of VEGF promoter i-motif, which leaves much room for development. Herein, we report the discovery of the natural oleanolic acid scaffold as a novel chemotype for the development of selective ligands of VEGF i-motif. A series of oleanolic acid derivatives as VEGF promoter i-motif ligands were synthesized. Subsequent evaluations showed that 3c could selectively bind to and stabilize VEGF promoter i-motif without significant binding to G-quadruplex, duplex DNA, and other oncogene i-motifs. Cell-based assays indicated that 3c could effectively downregulate VEGF gene transcription and expression in MCF-7 cells, inhibit tumor cells proliferation and migration, and induce cancer cells apoptosis. This work provides evidence of VEGF promoter i-motif as an anticancer target and will facilitate future efforts for the discovery of oleanolic acid-based selective ligands of VEGF promoter i-motif.

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Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

International Journal of Molecular Sciences ◽

10.3390/ijms22083825 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3825

Author(s):

Beata Tylińska ◽

Benita Wiatrak ◽

Żaneta Czyżnikowska ◽

Aneta Cieśla-Niechwiadowicz ◽

Elżbieta Gębarowska ◽

...

Keyword(s):

Molecular Docking ◽

Anticancer Agents ◽

Topoisomerase Ii ◽

Colon Adenocarcinoma ◽

Docking Study ◽

Biological Evaluation ◽

Dermal Fibroblasts ◽

Pyrimidine Derivatives ◽

Molecular Docking Study

In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking.

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Synthesis and biological evaluation of 4β-benzoxazolepodophyllotoxin hybrids as DNA topoisomerase-II targeting anticancer agents

RSC Advances ◽

10.1039/c5ra15366b ◽

2015 ◽

Vol 5 (118) ◽

pp. 97314-97319 ◽

Cited By ~ 2

Author(s):

Suresh Paidakula ◽

Shravankumar Kankala ◽

Ranjith kumar Kankala ◽

Bhasker Juluru ◽

Sreekantha B. Jonnalagadda ◽

...

Keyword(s):

Anticancer Agents ◽

Topoisomerase Ii ◽

Biological Evaluation ◽

Dna Topoisomerase Ii ◽

Human Tumour ◽

Dna Topoisomerase ◽

Tumour Cell Lines ◽

Hoechst Staining ◽

Synthesis And Biological Evaluation ◽

Human Tumour Cell Lines

A series of new 4β-benzoxazolepodophyllotoxin compounds (9a–j) were prepared and screened for molecular modelling and cytotoxicity against various human tumour cell lines. Cell apoptosis evaluation was performed using Hoechst staining.

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Ethanolic extract of mangosteen (Garcinia mangostana) pericarp as sensitivity enhancer of doxorubicin on MCF-7 cells by inhibiting P-glycoprotein

Nusantara Bioscience ◽

10.13057/nusbiosci/n110109 ◽

2019 ◽

Vol 11 (1) ◽

pp. 49-55 ◽

Cited By ~ 1

Author(s):

NI PUTU LINDA LAKSMIANI

Keyword(s):

Side Effects ◽

Cell Viability ◽

Anticancer Agents ◽

In Silico ◽

Cytotoxic Effect ◽

Ethanolic Extract ◽

Garcinia Mangostana ◽

P Glycoprotein ◽

Viability Percentage ◽

Mcf 7

Abstract. Laksmiani NPL. 2019. Ethanolic extract of mangosteen (Garcinia mangostana) pericarp as sensitivity enhancer of doxorubicin on MCF-7 cells by inhibiting P-glycoprotein. Nusantara Bioscience 11: 49-55. Generally, doxorubicin is used in combination with other anticancer agents. Reduction side effects tend to be better in combination use than the use of single doxorubicin. Therefore the development of anticancer agents with low side effects and combination agents that decrease the side effects of doxorubicin still need to be pursued. The use of doxorubicin also shows a phenomenon of resistance due to over-expression of P-glycoprotein (Pgp). The research was conducted to evaluate the cytotoxic effect of lower dose doxorubicin combine with ethanolic extract of mangosteen pericarp (EEMP) on MCF-7 cells and determine the mechanism of alpha (a)-mangostin as the active compound in EEMP that contribute increasing sensitivity of doxorubicin on MCF-7 through Pgp by in silico. The cytotoxic activity was observed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Molecular docking with 4.2 autodock program was used to evaluate the interaction of a-mangostin with Pgp. EEMP has IC50 of 54 μg/mL on MCF-7 cells while for doxorubicin has IC50 of 1392 nM. Exposure EEMP enhanced cytotoxic effect of doxorubicin on MCF-7 cells. Solely doxorubicin 750 nM treatment gave cell viability percentage 94.98%, but when combined with EEMP 22.5 μg/mL, the cell viability percentage was reduced to 16.91%. This shows that EEMP potent to be used as a combination agent for doxorubicin chemotherapy. The in silico assay demonstrate that a-mangostin has an affinity for Pgp with binding energy of -6.13 kcal/mol. Keywords: EEMP, doxorubicin, MCF-7, Pgp, combination

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