Design, synthesis and biological evaluation of 2-(phenoxymethyl)-5-phenyl-1,3,4-oxadiazole derivatives as anti-breast cancer agents

Lakshmithendral, K.; Saravanan, K.; Elancheran, R.; Archana, K.; Manikandan, N.; Arjun, H. A.; Ramanathan, Meena; Lokanath, N.K.; Kabilan, S.

doi:10.1016/j.ejmech.2019.02.033

Cited by 49 publications

(18 citation statements)

References 33 publications

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“…A molecular docking approach was followed for designing of benzohydrazide derivatives by using Schrödinger (Maestro 11.2) software (Maestro, 2016). The 3D structure of the human androgen receptor alpha ligand binding domain with the Selective Androgen Receptor Modulators (SARM) inhibitor (PDB ID: 3V49) was obtained from the Protein Data Bank, refined the structure and was used for the study (Nique et al, 2012; Lakshmithendral et al, 2019). Docking studies were carried out to find the potential binding affinity and the interaction between the compounds (6a-k ) and AR protein, as shown in Figure S1.…”

Section: Resultsmentioning

confidence: 99%

RETRACTED: Design, Synthesis, and Biological Evaluation of (E)-N'-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide Derivatives as Anti-prostate Cancer Agents

Arjun

Elancheran

Manikandan³

et al. 2019

Front. Chem.

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Prostate Cancer (PCa) is the most frequently diagnosed cancer in men in their late '50s. PCa growth is mainly due to the activation of the androgen receptor by androgens. The treatment for PCa may involve surgery, hormonal therapy, and oral chemotherapeutic drugs. A structural based molecular docking approach revealed the findings of (E)-N'-((1-chloro-3,4-dihydronaphthalen-2-yl)methylene)benzohydrazide derivatives, where the possible binding modes of the compounds with protein (PDB ID: 3V49) are shown. The compounds ( 6a-k ) were synthesized and characterized by using conventional methods. The compounds, 6g, 6j , and 6k were reconfirmed through single crystal X-ray diffraction (XRD). Further, the compounds (6a-k) and standard drug were evaluated against human prostate cancer cell lines, LNCaP and PC-3 and the non-cancerous cell line, 3T3. Among these compounds, 6g and 6j showed higher cytotoxicity, and 6g exhibited dose-dependent activity and reduced cell viability. The mechanism of action was observed through the induced apoptosis and was further confirmed by western blot and ELISA. Molecular dynamics simulation studies were carried out to calculate the interaction and the stability of the protein-ligand complex in motion. ADME properties were predicted for all the tested compounds. These findings may give vital information for further development.

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Section: Resultsmentioning

confidence: 99%

RETRACTED: Design, Synthesis, and Biological Evaluation of (E)-N'-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide Derivatives as Anti-prostate Cancer Agents

Arjun

Elancheran

Manikandan³

et al. 2019

Front. Chem.

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“…Additionally, the compounds 4a – 4j were achieved by the reaction of compounds 3a and 3b with benzoic acid and phosphoryl chloride refluxing at 100 °C in the presence of ethanol for 8 h ( Scheme ). Column chromatography was used to purify all the compounds, and spectroscopic techniques confirmed their structures . The yields and melting points of the compounds were recorded and shown in the Experimental Section .…”

Section: Resultsmentioning

confidence: 99%

“…Column chromatography was used to purify all the compounds, and spectroscopic techniques confirmed their structures. [25] The yields and melting points of the compounds were recorded and shown in the Experimental Section. The compound 4i was recrystallized in DMSO/ chloroform by slow evaporation at room temperature.…”

Section: Chemistrymentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of 2‐(2‐Bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole Derivatives as Possible Anti‐Breast Cancer Agents

Ananth

Manikandan²,

Rajan³

et al. 2020

Chemistry & Biodiversity

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Breast Cancer (BCa) is the most often diagnosed cancer among women who were in the late 1940’s. Breast cancer growth is largely dependent on the expression of estrogen and progesterone receptor. Breast cancer cells may have one, both, or none of these receptors. The treatment for breast cancer may involve surgery, hormonal therapy (Tamoxifen, an aromatase inhibitor, etc.) and oral chemotherapeutic drugs. The molecular docking technique reported the findings on the potential binding modes of the 2‐(2‐bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole derivatives with the estrogen receptor (PDB ID: 3ERT). The 1,3,4‐oxadiazole derivatives 4a–4j have been synthesized and described by spectroscopic method. 2‐(2‐Bromo‐6‐nitrophenyl)‐5‐(4‐bromophenyl)‐1,3,4‐oxadiazole (4c) was reconfirmed by single‐crystal XRD. All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF‐7, MDA‐MB‐453 and MCF‐10A non‐cancer cell lines. The compounds with the methoxy (in 4c) and methyl (in 4j) substitution were shown to have significant cytotoxicity, with 4c showing dose‐dependent activation and decreased cell viability. The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. Molecular dynamics simulations were made for hit molecule 4c to study the stability and interaction of the protein−ligand complex. The toxicity properties of ADME were calculated for all the compounds. All these results provide essential information for further clinical trials.

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“…Compounds based on oxidiazoles and isatin moieties, well known for vigorous research for anticancer, antiparasitic activities and such type of compounds were also screened on the basis of their structure similarities (Bhatt et al, 2020;Ivanova et al, 2007;Lakshmithendral et al, 2019;Mendel et al, 2003;Serafim et al, 2017;Venkatarao et al, 2019;Zhang et al, 2011). Other heterocyclic moieties with azo based structures and antibacterial, antitumor or anticancer activities were also screened (Bhatt et al, 2018;Jha & Ramarao, 2018;Tamokou et al, 2016).…”

Section: Selection Of Candidate Drugs That Were Screenedmentioning

confidence: 99%

Determination of potential inhibitors based on isatin derivatives against SARS-CoV-2 main protease (m^pro): a molecular docking, molecular dynamics and structure-activity relationship studies

Badavath

Kumar

Samanta

et al. 2020

Journal of Biomolecular Structure and Dynamics

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SARS-COV-2, the novel coronavirus and root of global pandemic COVID-19 caused a severe health threat throughout the world. Lack of specific treatments raised an effort to find potential inhibitors for the viral proteins. The recently invented crystal structure of SARS-CoV-2 main protease (M pro) and its key role in viral replication; non-resemblance to any human protease makes it a perfect target for inhibitor research. This article reports a computer-aided drug design (CADD) approach for the screening of 118 compounds with 16 distinct heterocyclic moieties in comparison with 5 natural products and 7 repurposed drugs. Molecular docking analysis against M pro protein were performed finding isatin linked with a oxidiazoles (A2 and A4) derivatives to have the best docking scores of À11.22 kcal/ mol and À11.15 kcal/mol respectively. Structure-activity relationship studies showed a good comparison with a known active M pro inhibitor and repurposed drug ebselen with an IC 50 value of À0.67 lM. Molecular Dynamics (MD) simulations for 50 ns were performed for A2 and A4 supporting the stability of the two compounds within the binding pocket, largely at the S1, S2 and S4 domains with high binding energy suggesting their suitability as potential inhibitors of M pro for SARS-CoV-2.

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Design, synthesis and biological evaluation of 2-(phenoxymethyl)-5-phenyl-1,3,4-oxadiazole derivatives as anti-breast cancer agents

Cited by 49 publications

References 33 publications

RETRACTED: Design, Synthesis, and Biological Evaluation of (E)-N'-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide Derivatives as Anti-prostate Cancer Agents

RETRACTED: Design, Synthesis, and Biological Evaluation of (E)-N'-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide Derivatives as Anti-prostate Cancer Agents

Design, Synthesis, and Biological Evaluation of 2‐(2‐Bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole Derivatives as Possible Anti‐Breast Cancer Agents

Determination of potential inhibitors based on isatin derivatives against SARS-CoV-2 main protease (m^pro): a molecular docking, molecular dynamics and structure-activity relationship studies

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Design, synthesis and biological evaluation of 2-(phenoxymethyl)-5-phenyl-1,3,4-oxadiazole derivatives as anti-breast cancer agents

Cited by 49 publications

References 33 publications

RETRACTED: Design, Synthesis, and Biological Evaluation of (E)-N'-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide Derivatives as Anti-prostate Cancer Agents

RETRACTED: Design, Synthesis, and Biological Evaluation of (E)-N'-((1-Chloro-3,4-Dihydronaphthalen-2-yl)Methylene)Benzohydrazide Derivatives as Anti-prostate Cancer Agents

Design, Synthesis, and Biological Evaluation of 2‐(2‐Bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole Derivatives as Possible Anti‐Breast Cancer Agents

Determination of potential inhibitors based on isatin derivatives against SARS-CoV-2 main protease (mpro): a molecular docking, molecular dynamics and structure-activity relationship studies

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Determination of potential inhibitors based on isatin derivatives against SARS-CoV-2 main protease (m^pro): a molecular docking, molecular dynamics and structure-activity relationship studies