Design, Synthesis and Evaluation of Antiproliferative Activity of New Benzimidazolehydrazones

Onnis, Valentina; Demurtas, Monica; Deplano, Alessandro; Baldisserotto, Anna; Manfredini, Stefano; Pacifico, Salvatore; Liekens, Sandra; Balzarini, Jan

doi:10.3390/molecules21050579

Cited by 36 publications

(34 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is evident from the results of CCD-16-Co cells that tolerated approximately 5000 nM MLT-401. Similar effects were observed with other arylidene derivatives studied using various cancer models [9, 27]. The selective inhibition of cancerous cells over normal cells both in normoxic and marginal hypoxic conditions shows that the molecule works downstream of the hypoxic conditions.…”

Section: Discussionsupporting

confidence: 65%

Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

Bin-Jaliah¹

2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Cancer cells in vivo develop resistance to many anti-tumor drugs. One known factor to influence such drug resistance is hypoxia, which is an important component of the tumor microenvironment. Standard cancer lines mostly do not exhibit a cellular hypoxic microenvironment and there is a paucity of information on the efficacy of lead molecules in both cellular- and environment-induced hypoxic conditions. Therefore, in the present study, we have evaluated the efficacy of the arylidene derivative MLT-401, a lead molecule showing activity against colorectal cancer model using the HCT 116 cell line and CCD-80-C control cells in normoxic and natural (marginal) hypoxic conditions, which is usually observed in high-altitude regions. Methods: The efficacy of MLT-401 on HCT 116 and CCD-80-C cells were tested in both normoxia and marginal hypoxia conditions. MTT assay was used to evaluate cell proliferation, Annexin V binding assay for apoptotic cell quantification and PI staining for cell cycle were done by flow cytometry. Induction of pro-apoptotic marker BAX and anti-apoptotic Bcl-2 were assessed by western blot. Bcl-2/BAX ratio was calculated based on protein expression by western blotting and bands were quantified by Image J software. Results: Analysis of cell proliferation showed an average 10-fold reduction in the inhibition of HCT 116 cells in hypoxic conditions with approximately 500 nM MLT-401, while there was no significant change noted in marginal hypoxic conditions. A proportionate increase in the number of apoptotic cells and large M4 fraction of 10.5% and 26.7% of HCT116 against 6.3% of control cells in cell cycle assessment with MLT-401 concentrations ranging from 250 to 500 nM respectively clearly demonstrated anti-cancer activity. A Bcl-2/BAX ratio of < 1 showed that the induction of apoptosis was the gross mechanism underlying the inhibition of HCT 116 cells by MLT-401. Conclusion: Collectively, these results show MLT-401 as an effective anti-colorectal cancer lead molecule irrespective of normoxia or natural hypoxia.

show abstract

Section: Discussionsupporting

confidence: 65%

Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

Bin-Jaliah¹

2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…The structures of the novel compounds were confirmed by using IR, 1 H NMR, 13 C NMR spectra, and mass analysis. Spectral (IR, 1 H NMR, 13 C NMR) data of the synthesized compounds (2a-k) were consistent with the literature [32][33][34]. The IR spectra of the products are characterized by the presence of absorption bands at 2936-2730 and 1588-1441 cm À1 corresponding to the aliphatic C-H, C --C, and C --N functions in the structure.…”

Section: Resultsmentioning

confidence: 96%

“…In conclusion, we synthesized 2-substitutedbenzyl-4(7)-phenyl-1H-benzo[d]imidazole derivatives (2a-k) and characterized by using IR, 1 H NMR, 13 C NMR spectra, and mass analysis. Tyrosinase inhibitory effects and antioxidant activities of the synthesized benzimidazole derivative compounds were evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…The reason for this interest, the compounds bearing benzimidazole ring were obtained biologically active molecules. These pharmacological activities are antimicrobial , antiproliferative , antibacterial , receptor antagonists , antitumor activity , cytotoxic activity , antihelmintic resistance , sirtuin inhibitor activity , anti‐MRSA and anti‐VRE agonists , anticancer , antitubercular activity , hepatitis C virus inhibitor , antidiabetic , antihypertensive , and lipase inhibition activity .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of Some Novel 2‐Substitutedbenzyl‐(4)7‐phenyl‐1H‐benzo[d]imidazoles in Mild Conditions as Potent Anti‐Tyrosinase and Antioxidant Agents

Doğan

Özel

Birinci

et al. 2016

Archiv der Pharmazie

View full text Add to dashboard Cite

Novel 2-substitutedbenzyl-4(7)-phenyl-1H-benzo[d]imidazole compounds were synthesized and characterized. Although 2a and 2b were reported previously in the literature, 11 compounds were synthesized (nine of them were newly synthesized) and the tyrosinase inhibitory effects and antioxidant activities of these compounds were studied for the first time. All of the synthesized compounds displayed certain inhibitory effects on tyrosinase, with IC values ranging from 37.86 ± 0.24 to 75.81 ± 2.49 μM. Among the compounds, 2j exhibited similar tyrosinase inhibitory effect (IC = 37.86 ± 0.24 µM) to the positive control, kojic acid (IC = 21.93 ± 0.11 µM). Kinetic studies revealed it to act as non-competitive tyrosinase inhibitor with a K value of 50.2 µM. The antioxidant activities of the compounds were investigated by using in vitro antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). All of these results indicated that the compounds might have potential application as tyrosinase inhibitors.

show abstract

“…Many studies have revealed the importance of benzimidazoles as anticancer agents including bendamustine, dovitinib, Hoechst 33342, and Hoechst 33258 (Fig. 1) [14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative, Cytotoxic, and Apoptotic Effects of New Benzimidazole Derivatives Bearing Hydrazone Moiety

Çevik

Sağlık

Korkut

et al. 2017

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

in Wiley Online Library (wileyonlinelibrary.com).In order to take the advantages of the anticancer properties of benzimidazoles and hydrazones, we synthesized new 4-(5-chloro-1H-benzimidazol-2-yl)-benzoic acid benzylidene hydrazide derivatives (3a-3t) and evaluated their anticancer activity against A549 (human lung adenocarcinoma) and MCF-7 (human breast adenocarcinoma) cells. The structures of the compounds (3a-3t) were confirmed by IR, 1 H-NMR, 13 C-NMR, mass spectroscopy, and elemental analyses. Antiproliferative activities of the compounds were evaluated using MTT assay, BrdU method, and flow cytometric analysis. In addition, with purpose of determining selectivity the cytotoxic activities of the final compounds were screened against healthy NIH3T3 cell line (mouse vembryonic fibroblast cells). Among the tested compounds 3e and 3f showed significant cytotoxic activity against A549 and MCF-7 cancer cells with an IC 50 value of 0.0316 μM. Furthermore, compound 3p showed remarkable cytotoxic activity against MCF-7 comparing with standard drug cisplatin. Annexin V-FITC assay also suggested that this compounds induced cell death by apoptosis.

show abstract

Design, Synthesis and Evaluation of Antiproliferative Activity of New Benzimidazolehydrazones

Cited by 36 publications

References 24 publications

Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model

Synthesis of Some Novel 2‐Substitutedbenzyl‐(4)7‐phenyl‐1H‐benzo[d]imidazoles in Mild Conditions as Potent Anti‐Tyrosinase and Antioxidant Agents

Antiproliferative, Cytotoxic, and Apoptotic Effects of New Benzimidazole Derivatives Bearing Hydrazone Moiety

Contact Info

Product

Resources

About