A Facile Synthesis of Novel Bis‐(indolyl)‐1,3,4‐oxadiazoles as Potent Cytotoxic Agents

Kumar, Dalip; Arun, V.; Kumar, Nikhil; Acosta, Glen; Noel, Brett; Shah, Kavita

doi:10.1002/cmdc.201200363

Cited by 18 publications

(14 citation statements)

References 55 publications

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“…The indole ring system is one of the most crucial heterocycles that has found versatile pharmacological implications in medicinal chemistry. , Many of the natural and synthetic indole-based heterocycles with various functionalities are reported as potential anticancer molecules. − Recently, the diverse biological activities of hydrazide–hydrozones have attracted the researchers to develop their heterocyclic analogues as efficient chemotherapeutic agents. − …”

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confidence: 99%

Development of Novel Bis(indolyl)-hydrazide–Hydrazone Derivatives as Potent Microtubule-Targeting Cytotoxic Agents against A549 Lung Cancer Cells

et al. 2016

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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.

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Development of Novel Bis(indolyl)-hydrazide–Hydrazone Derivatives as Potent Microtubule-Targeting Cytotoxic Agents against A549 Lung Cancer Cells

et al. 2016

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“…After completion of reaction content was neutralized with NaHCO 3 (Esterification reaction) filtered it to remove the salt, after that 0.003 mole hydrazine hydrate was added to above Ester and refluxed for 15 hours. Product was obtained by filtration and recrystallized it from ethanol to give pure compound [16][17][18][19] . As white solid (75% yield); mp = 142˚C; IR: (KBr cm (2,4 dichloro phenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-2-(3H-indol-3-yl) amino phenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-2-(3H -indol -3-yl …”

Section: Methodsmentioning

confidence: 99%

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2017

IJPSR

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Series of 1 of 1-[(3,5 diphenyl substituted ) -4,5-dihydro-1H-pyrazol-1-yl]-2-(3H-indol-3-yl) ethan-1-one (5a-5j) derivatives were synthesized by the reaction between indole 3 acetic acid hydrazide and various chalcones (3a-3j). The Chalcones were prepared by Claisen-Schmidt condensation reaction in which substituted aromatic aldehydes was treated with simple acetophenone(aromatic ketones) in presence of 20% base(NaOH) and indole 3 acetic acid hydrazide was prepared by reaction between 3 indole acetic acid with hydrazide. The synthesized new compounds were identified by spectral studies and elemental analysis, and were evaluated in vitro for their antimicrobial activity using standard agar diffusion method and using four bacterial strains (Bacillus, Pseudomonas, Escherichia coli and Staphylococcus) and two fungal strains (Sclerotium rolfsii & Macrophomina phaseolina) most of compounds such 5c.5a,5b,5f,5g i.e 1-[5-(4-Chloro phenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl] -2 -(3H-indol-3-yl) ethan-1-one (5c), 1-(3, 5-

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“…The starting materials 4,4,4trifluoro-1,3-diphenylbut-2-en-1-ones were prepared according to literature procedure. [64][65][66][67][68] Organocatalytic…”

Section: Syn Thesismentioning

confidence: 99%

The Catalytic Asymmetric Construction of Trifluoromethylated Quaternary Carbon-Containing Thiochromans

Chen¹,

Wang²,

Wen³

et al. 2019

Synthesis

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Trifluoromethylated chiral quaternary stereogenic carbon center at 2-position of thiochromans has been constructed through organocatalyzed Michael-aldol reaction. With quinine squaramide as catalyst, the reaction of 2-mercaptobenzaldehyde with β-aryl-β-CF3 enones or β-alkyl-β-CF3 enones gave 2-CF3-thiochromans bearing three contiguous stereogenic centers in good to excellent diastereoselectivities, enantioselectivities, and yields.

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A Facile Synthesis of Novel Bis‐(indolyl)‐1,3,4‐oxadiazoles as Potent Cytotoxic Agents

Cited by 18 publications

References 55 publications

Development of Novel Bis(indolyl)-hydrazide–Hydrazone Derivatives as Potent Microtubule-Targeting Cytotoxic Agents against A549 Lung Cancer Cells

Development of Novel Bis(indolyl)-hydrazide–Hydrazone Derivatives as Potent Microtubule-Targeting Cytotoxic Agents against A549 Lung Cancer Cells

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The Catalytic Asymmetric Construction of Trifluoromethylated Quaternary Carbon-Containing Thiochromans

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