Inhibitory growth evaluation and apoptosis induction in MCF-7 cancer cells by new 5-aryl-2-butylthio-1,3,4-oxadiazole derivatives

Khanam, Rashmin; Ahmad, Kamal; Hejazi, Iram Iqbal; Siddique, Ibrar Ahmad; Kumar, Vikash; Bhat, Abdul Roouf; Azam, Amir; Athar, Fareeda

doi:10.1007/s00280-017-3414-6

Cited by 26 publications

(10 citation statements)

References 35 publications

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“…DAPI cannot pass through the membrane of live cells very effectively. Due to the condensed nucleus, the apoptotic cells appeared as bright colored on staining with DAPI; this is a distinctive characteristic of apoptosis . Hence, this study distinguishes live cells from apoptotic cells by observing the nuclear morphology to see the effect of 8 k in A‐549 cells.…”

Section: Resultsmentioning

confidence: 96%

Synthesis, Anticancer Evaluation and DNA‐Binding Spectroscopic Insights of Quinoline‐Based 1,3,4‐Oxadiazole‐1,2,3‐triazole Conjugates

et al. 2019

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The present work involves a pharmacophore hybridization strategy to combine key biologically active scaffolds. The study led to the synthesis of quinoline based oxadiazole‐triazole conjugates with favorable physicochemical properties as anti‐cancer agents. Among the synthesized compounds 8(a–p), in vitro screening against a panel of four cancer cell lines identified compound 8k, with o‐chloro substitution on the phenyl ring, as potent against human lung carcinoma (A‐549) cells (IC50 =5.6 μM), while showing no significant cytotoxicity upto 200 μM concentration in normal cells. Compound 8 k with o‐chloro substitution induced nuclear morphological changes in A‐549 cells as visualized by DAPI (4,6‐diamidino‐2‐phenylindole) and was shown to bind firmly with A−T rich region in DNA. Changes in DNA topology studied through gel electrophoresis and groove mode of binding to ct‐DNA through multi‐spectroscopic techniques were observed, further validated by molecular docking studies. Overall, the study illustrates successful hybridization strategy leading to compound 8 k as promising anticancer agent for further structural optimization and biological evaluation.

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Section: Resultsmentioning

confidence: 96%

Synthesis, Anticancer Evaluation and DNA‐Binding Spectroscopic Insights of Quinoline‐Based 1,3,4‐Oxadiazole‐1,2,3‐triazole Conjugates

et al. 2019

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“…Flow cytometry analysis showed that cancer cells were arrested in the G0/G1 phase of the cell cycle. Western blotting studies (an electrophoresis-based method for the detection of specific proteins [67]) showed high activation of apoptotic protein caspase-3 and decreased expression of antiapoptotic protein Bcl-2 [68].…”

Section: Anti-proliferative Effects Of 134-oxadiazole Derivativesmentioning

confidence: 99%

Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole

2018

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Compounds containing 1,3,4-oxadiazole ring in their structure are characterised by multidirectional biological activity. Their anti-proliferative effects associated with various mechanisms, such as inhibition of growth factors, enzymes, kinases and others, deserve attention. The activity of these compounds was tested on cell lines of various cancers. In most publications, the most active derivatives of 1,3,4-oxadiazole exceeded the effect of reference drugs, so they may become the main new anti-cancer drugs in the future.

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“…In a previous investigation on 5-aryl-2-butylthio-1, 3, 4-oxadiazole derivatives ( 4a–5f ), we observed antiproliferative effects of these compounds on MCF-7 breast cancer cells as a result of the induction of apoptosis [1]. In the present study, we further explored the potential of these compounds as antioxidants and STAT3 inhibitors through computational analyses to establish the authenticity of these derivatives as potent anticancer agents because antioxidants and STAT3 inhibitors are known to play prominent roles against the progression of cancer.…”

Section: Introductionmentioning

confidence: 77%

“…From previous cytotoxic studies, the IC 50 value for compound 5e was found to be 2.45 ± 1.03 µg/mL for MCF-7 cancer cells [1]. Thus, we investigated the effect of compound 5e on STAT3 in MCF-7 cancer cells at the same concentrations via Western blot assay.…”

Section: Resultsmentioning

confidence: 97%

“…The synthesized compounds (Scheme 1) ( 4a–5f ) reported by us previously [1] were tested for their antioxidant potential using the DPPH [37], NO [38], H 2 O 2 [2], O 2 - [39], total reducing capacity [2] and total antioxidant assays [40]. The results for the in-vitro antioxidant assays for the synthesized compounds and the standard antioxidant were compared.

Scheme 1Schematic representation for synthesis protocol for compounds (4a–5f) .…”

Section: Resultsmentioning

confidence: 99%

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Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors

Khanam

Hejazi

Shahabuddin

et al. 2019

Journal of Pharmaceutical Analysis

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1, 3, 4-Oxadiazole derivatives (4a–5f) were previously synthesized to investigate their anticancer properties. However, studies relating to their antioxidant potential and signal transducer and activator of transcription (STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole derivatives ( 4a–5f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical (DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among all the derivatives, compound 5e displayed high antioxidant activities than the standard antioxidant L -ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound 5e . Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy released in direct binding with the SH2 domain of STAT3 was the highest for compound 5e (-9.91kcal/mol). Through virtual screening, compound 5e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound 5e decreased the activation of STAT3 as observed with Western blot. In brief, compound 5e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.

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Inhibitory growth evaluation and apoptosis induction in MCF-7 cancer cells by new 5-aryl-2-butylthio-1,3,4-oxadiazole derivatives

Abstract: Based on the results of in vitro studies, it could be concluded that compound 5e showed a significant inhibitory growth effect on MCF-7 cells and have the potential to be developed as lead molecule and further structural modifications may result in promising new anticancer agents.

Cited by 26 publications

References 35 publications

Synthesis, Anticancer Evaluation and DNA‐Binding Spectroscopic Insights of Quinoline‐Based 1,3,4‐Oxadiazole‐1,2,3‐triazole Conjugates

Synthesis, Anticancer Evaluation and DNA‐Binding Spectroscopic Insights of Quinoline‐Based 1,3,4‐Oxadiazole‐1,2,3‐triazole Conjugates

Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole

Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors

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