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DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kumar, Dalip | - |
dc.date.accessioned | 2021-10-27T04:19:32Z | - |
dc.date.available | 2021-10-27T04:19:32Z | - |
dc.date.issued | 2016-04-25 | - |
dc.identifier.uri | https://pubs.acs.org/doi/10.1021/acs.biochem.5b01127 | - |
dc.identifier.uri | http://dspace.bits-pilani.ac.in:8080/xmlui/handle/123456789/3028 | - |
dc.description.abstract | The biological significance of microtubules makes them a validated target of cancer therapy. In this study, we have utilized indole, an important pharmacological scaffold, to synthesize novel bis(indolyl)-hydrazide–hydrazone derivatives (NMK-BH compounds) and recognized NMK-BH3 as the most effective one in inhibiting A549 cell proliferation and assembly of tissue-purified tubulin. Cell viability experiments showed that NMK-BH3 inhibited proliferation of human lung adenocarcinoma (A549) cells, normal human lung fibroblasts (WI38) and peripheral blood mononuclear cells (PBMC) with IC50 values of ∼2, 48.5, and 62 μM, respectively. Thus, the relatively high cytotoxicity of NMK-BH3 toward lung carcinoma (A549) cells over normal lung fibroblasts (WI38) and PBMC confers a therapeutic advantage of reduced host toxicity. Flow cytometry, Western blot, and immunofluorescence studies in the A549 cell line revealed that NMK-BH3 induced G2/M arrest, mitochondrial depolarization, and apoptosis by depolymerizing the cellular interphase and spindle microtubules. Consistent with these observations, study in cell free system revealed that NMK-BH3 inhibited the microtubule assembly with an IC50 value of ∼7.5 μM. The tubulin–ligand interaction study using fluorescence spectroscopy indicated that NMK-BH3 exhibited strong and specific tubulin binding with a dissociation constant of ∼1.4 μM at a single site, very close to colchicine site, on β-tubulin. Collectively, these findings explore the cytotoxic potential of NMK-BH3 by targeting the microtubules and inspire its development as a potential candidate for lung cancer chemotherapy. | en_US |
dc.language.iso | en | en_US |
dc.publisher | ACS | en_US |
dc.subject | Chemistry | en_US |
dc.subject | Cancer | en_US |
dc.subject | Apoptosis | en_US |
dc.subject | Fluorescence | en_US |
dc.title | Development of Novel Bis(indolyl)-hydrazide–Hydrazone Derivatives as Potent Microtubule-Targeting Cytotoxic Agents against A549 Lung Cancer Cells | en_US |
dc.type | Article | en_US |
Appears in Collections: | Department of Chemistry |
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