Furan-2-carboxamide derivative, a novel microtubule stabilizing agent induces mitotic arrest and potentiates apoptosis in cancer cells

Shwetha, B.; Sudhanva, MS; Jagadeesha, Gullahalli S.; Thimmegowda, N. R.; Vivek, H. K.; Sridhar, B.; Thimmaiah, Κ. N.; Kumar, C. S. Ananda; Rangappa, Shobith; Rangappa, Kanchugarakoppal S.

doi:10.1016/j.bioorg.2020.104586

Cited by 17 publications

(7 citation statements)

References 45 publications

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“…Several 1,8-Naphthyridine derivatives have gained the attention of researchers for their anticancer properties and SAR studies on their efficacy as antitumor active compounds have been reported [21]. Furthermore, many other heterocyclic compounds such as indole, furano, isoxazole derivatives characterized by a carboxamide substituent have shown interesting anti-proliferative activity against different cancer cell lines [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells

et al. 2022

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1,8-naphthyridine-3-carboxamide structures were previously identified as a promising scaffold from which to obtain CB2R agonists with anticancer and anti-inflammatory activity. This work describes the synthesis and functional characterization of new 1,8-naphthyridin-2(1H)-one-3-carboxamides with high affinity and selectivity for CB2R. The new compounds were able to pharmacologically modulate the cAMP response without modulating CB2R-dependent β-arrestin2 recruitment. These structures were also evaluated for their anti-cancer activity against SH-SY5Y and SK-N-BE cells. They were able to reduce the cell viability of both neuroblastoma cancer cell lines with micromolar potency (IC50 of FG158a = 11.8 μM and FG160a = 13.2 μM in SH-SY5Y cells) by a CB2R-mediated mechanism. Finally, in SH-SY5Y cells one of the newly synthesized compounds, FG158a, was able to modulate ERK1/2 expression by a CB2R-mediated effect, thus suggesting that this signaling pathway might be involved in its potential anti-cancer effect.

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Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells

et al. 2022

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“…HeLa, Jurkat, and HCT116 cells were used for the assay, and the assay was performed as described previously . The treated cells were allowed to incubate for 24 h and subjected for MMP assay as per th emanufacturer’s protocol (MAK159, Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

“…MTT assay was performed as described previously. 40 Cells treated with an increased concentration of TJ08 were subjected to MTT assay after 48 and 72 h of incubation with addition of thiazolyl blue tetrazolium bromide (MTT; Sigma; St Louis, MO, USA) and incubated additionally for 4 h. Insoluble formazan crystals were solubilized using 100 μL of DMSO, and absorbance was recorded at 570 nm using a Tecan Microplate Reader (Tecan Instruments, Switzerland). Error bars were calculated based on a minimum of three independent experiments and data represented as histogram.…”

Section: Methodsmentioning

confidence: 99%

“…HeLa, Jurkat, and HCT116 cells were used for the assay, and the assay was performed as described previously. 40 The treated cells were allowed to incubate for 24 h and subjected for MMP assay as per th emanufacturer’s protocol (MAK159, Sigma-Aldrich). Spectrophotometric absorbance of the plate was recorded at (λ ex = 490/λem = 525 nm) and (λ ex = 540/λem = 590 nm) for ratio analysis using Tecan Microplate Reader (Tecan Instruments, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

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Novel 1,2,5-Trisubstituted Benzimidazoles Potentiate Apoptosis by Mitochondrial Dysfunction in Panel of Cancer Cells

et al. 2022

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Synthetic small molecules have been very effective in decimating cancer cells by targeting various aberrantly overexpressed oncogenic proteins. These small molecules target proteins involved in cell cycle regulation, cell division, migration, invasion, angiogenesis, and other regulatory proteins to induce apoptosis in cancer cells. In this study, we have synthesized a novel 1,2,5-trisubstituted benzimidazole chemical library of small molecules and unveiled their anticancer potential against a panel of cancer cell lines such as Jurkat, K-562, MOLT-4, HeLa, HCT116, and MIA PaCa-2 cancer cells. The MTT assay and Trypan blue dye exclusion assay clearly unveiled the cytotoxic effect of methyl 1-benzyl-2-(4-fluoro-3-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylate (TJ08) and its potential to induce apoptosis with effective IC 50 of 1.88 ± 0.51, 1.89 ± 0.55, 2.05 ± 0.72, 2.11 ± 0.62, 3.04 ± 0.8, and 3.82 ± 0.25 μM against Jurkat, K562, MOLT-4, HeLa, HCT116, and MIA PaCa-2 cancer cell lines, respectively. Altered mitochondrial membrane potential was observed in HeLa, HCT116, and Jurkat cells due to TJ08 treatment, which was unveiled by JC10 staining. Induction of early and late apoptosis by TJ08 treatment was also unveiled by apoptotic analysis and immunofluorescence imaging. Cell cycle analysis distribution confirms the accumulation of cells in the S-phase in a dose-dependent manner.

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“…Many agents that disrupt cell functions by promoting or inhibiting microtubule assembly dynamics are mainstays of cancer treatment, however, many of them, especially those derived from natural sources, have limited use due to high toxicity, complex isolation processes, and difficulty in obtaining source material 18 , 19 . Thus, there is an urgent need to develop novel chemically synthetic small molecules that can modulate microtubule dynamics for the treatment of cancer.…”

Section: Introductionmentioning

confidence: 99%

Discovery of facile amides-functionalized rhodanine-3-acetic acid derivatives as potential anticancer agents by disrupting microtubule dynamics

Zhou

Liu

Meng³

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Microtubule dynamics are crucial for multiple cell functions, and cancer cells are particularly sensitive to microtubule-modulating agents. Here, we describe the design and synthesis of a series of ( Z )-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)- N -phenylacetamide derivatives and evaluation of their microtubule-modulating and anticancer activities in vitro . Proliferation assays identified I 20 as the most potent of the antiproliferative compounds, with 50% inhibitory concentrations ranging from 7.0 to 20.3 µM with A549, PC-3, and HepG2 human cancer cell lines. Compound I 20 also disrupted cancer A549 cell migration in a concentration-dependent manner. Immunofluorescence microscopy, transmission electron microscopy, and tubulin polymerisation assays suggested that compound I 20 promoted protofilament assembly. In support of this possibility, computational docking studies revealed a strong interaction between compound I 20 and tubulin Arg β 369, which is also the binding site for the anticancer drug Taxol. Our results suggest that ( Z )-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)- N -phenylacetamide derivatives could have utility for the development of microtubule-stabilising therapeutic agents.

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Furan-2-carboxamide derivative, a novel microtubule stabilizing agent induces mitotic arrest and potentiates apoptosis in cancer cells

Cited by 17 publications

References 45 publications

Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells

Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells

Novel 1,2,5-Trisubstituted Benzimidazoles Potentiate Apoptosis by Mitochondrial Dysfunction in Panel of Cancer Cells

Discovery of facile amides-functionalized rhodanine-3-acetic acid derivatives as potential anticancer agents by disrupting microtubule dynamics

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