Synthesis, Cytotoxicity Evaluation and Molecular Docking Studyof &lt;i&gt;N&lt;/i&gt;-Phenylpyrazoline Derivatives

Suma, Artania Adnin Tri; Wahyuningsih, Tutik Dwi; Mustofa, Mustofa

doi:10.22146/ijc.45777

Cited by 10 publications

(13 citation statements)

References 27 publications

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“…Docking result suggested that thioxanthones TX3 ‐ 6 were active against cancer cells that express EGFR protein. The cancer cells that express EGFR protein were in breast, [25] cervical, [26] lung, [27] and colorectal cancer [28] . Therefore, the synthesized thioxanthones TX3 ‐ 6 were evaluated through the MTT assay against breast (T47D), cervical (HeLa), colorectal (WiDr), and lung (A549) cancer cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…[20,21] In many cases, PDGFR protein is often overexpressed in the lung, [18] breast, [22] glioma, [23] and ovarian [24] cancer cell lines. While EGFR protein is expressed in breast, [25] cervical, [26] lung, [27] and colorectal [28] cancer cells. In our previous work on the molecular docking study of thioxanthone derivatives, it was revealed that the important factors influencing their binding energy were the presence of hydroxyl and halogen (i. e., chloro (Cl) and bromo (Br)) substituents.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Docking Approach For Design and Synthesis of Thioxanthone Derivatives as Anticancer Agents

et al. 2022

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Thioxanthone derivatives were docked, synthesized, and tested for their anticancer activity. The molecular docking results showed that 1-hydroxythioxanthone, 2-chloro-1-hydroxythioxanthone, and 4-chloro-1-hydroxythioxanthone gave lower binding energy than erlotinib demonstrating that those thioxanthones have stronger interaction in the active site of EGFR protein. The addition of one hydroxyl and chloro groups on 1-hydroxythioxanthone greatly enhanced its inhibition in EGFR protein. All thioxanthone derivatives had hydrogen bonding interaction with MET769 residue. The in vitro anti-cancer assay against all cancer cells (T47D, HeLa, WiDr, A549) revealed that 2-chloro-1-hydroxythioxanthone and 4-chloro-1hydroxythioxanthone gave lower IC 50 than 1-hydroxythioxanthone due to the addition of one chloro substituent. Meanwhile, 1,3-dihydroxythioxanthone exhibited the strongest anticancer activity, as well as the highest selectivity index (3.22-19.55) among the other thioxanthones. Based on these findings, 1,3-dihydroxythioxanthone is a potential anticancer drug candidate for further development in the future.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Docking Approach For Design and Synthesis of Thioxanthone Derivatives as Anticancer Agents

et al. 2022

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“…The last five years' studies found that the pyrazoline and N-phenyl pyrazoline derivatives targeted the EGFR. 12,13 The EGFR signaling pathway is a well-known signaling pathway that regulates cancer cell proliferation, tumor growth, and metastasis in cancers. Further, the human papillomavirus infection is well known as the main cause of cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Indones J Chem. 2019;19(4):1081-1090. doi:10.22146/ijc.45777 Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License 12.…”

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confidence: 99%

A Potent EGFR Inhibitor, N-Phenyl Pyrazoline Derivative Suppresses Aggressiveness and Cancer Stem Cell-Like Phenotype of Cervical Cancer Cells

Mustofa¹,

Satriyo²,

Suma³

et al. 2022

DDDT

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Objective Metastasis causes approximately 90% of cancer-related deaths, including in cervical cancer patients. Uncontrolled cell proliferation, migration, and cancer stemness act as critical events in primary tumor growth and cancer metastasis progression in cervical cancer. Here, we investigated the anti-proliferative, anti-migration, and cancer stemness inhibition activity of N-phenyl pyrazoline derivatives against cervical cancer cells. Methods The chalcone and phenylhydrazine were used to synthesize the N-phenyl pyrazoline 2/5 (P2 and P5). The MTT, colony formation, and wound healing assays were performed to evaluate the N-phenyl pyrazoline effect in HeLa cells. The N-phenyl pyrazoline’s protein target was predicted using SwissTargetPrediction and AutoDock Vina software. The Western blotting assay was performed to evaluate the target proteins. The public dataset analysis was used to confirm the clinical relevance of target protein in cervical cancer patients. Results N-phenyl pyrazoline 2 and 5 were successfully synthesized. The N-phenyl pyrazolines 2 and 5 exhibit cytotoxic effect in HeLa cell line with 20.26 µM, 4.708 µM of IC 50, respectively. Further study shows that the N-phenyl pyrazoline 5 suppresses the cell proliferation and migration ability of HeLa cell line in a dose-dependent manner. Target prediction and molecular docking reveal that EGFR and ERBB2 protein as the main target of the N-phenyl pyrazoline 5 compound. The N-phenyl pyrazoline 5 suppresses the EGFR expression level but not the total ERK1/2. Public data and GSEA analysis found that the EGFR high expression level is positively associated with poor survival, cancer metastasis-related signaling pathways, and cancer stem cell markers in cervical cancer patients. In addition, the N-phenyl pyrazoline 5 reduces the HeLa’s tumorsphere size and cancer stem cell marker, CD133. Conclusion N-phenyl pyrazoline 5 suppresses the cell viability, proliferation, migration, and cancer stem cell-like phenotype of cervical cancer cells via EGFR inhibition.

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“…Globally, cancer is one of the serious and dreadful diseases characterized by the uncontrolled, rapid, and pathological proliferation of cells (Chavan et al, 2018). In underdeveloped countries incidence and mortality rate due to cancer increases day to day because of the growth and aging of the population (Suma et al, 2019). As per a survey by GLOBO-CAN in 2018, over 18.1 million new cancer cases and 9.6 million deaths till now and the cases may gradually raise up to 23.6 million by 2030 (Suma et al, 2019;Santosh et al, 2019;Jemal et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, molecular docking and in vitro anticancer activity of 3-(4-methoxyphenyl)-5-substituted phenyl-2-pyrazoline-1- carbothioamide

Sahu

Rajapandi

Maji

et al. 2021

ijrps

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In the present study, eight numbers of new 3- (4-methoxy phenyl)-5-substituted phenyl-2-pyrazoline-1-carbothioamide (5a-h) have been synthesized from 1- (4-methoxy phenyl)-3- (substituted phenyl)-prop-2-en-1-one (3a-h) and structurally characterized by using FT-IR, 1H NMR, 13C NMR, Mass and Elemental analysis. The synthesized molecules were biologically evaluated for their in vitro anticancer activity against human breast adenocarcinoma (MCF-7), liver cancer (Hep-G2) and leukaemia cancer (K-562) cell line using Sulforhodamine B (SRB) bioassay technique. From the all synthesized compounds 5a, 5c, 5d, and 5e exhibited potent anticancer activity (GI50= <10µg/ml) as compared to the controlled drug 5-Fluorouracil (5-FU) (GI50=44.5µg/ml) and Adriamycin (ADR) (GI50= <10µg/ml) on MCF-7 cell lines. Besides this, all the synthesized compounds have exhibited moderate activity against human liver cancer (Hep-G2) and leukaemia cancer (K-562) cell lines. In addition, molecular docking studies were also explored in order to study the probable binding specificity into the active site of Epidermal Growth Factor Receptor tyrosine kinase (EGFR) (PDB ID: 1M17) using Molegro Virtual Docker Evaluation 2013 6.0.1 (MVD). Based on the molecular docking result, it was found that compound 5a exhibited the best interaction with the above target (i.e., EGFR) by interacting with specific amino acid residues such as: Thr 766, Gin 767, Thr 830, Cys 575, Ala 719 and Met 769.

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Synthesis, Cytotoxicity Evaluation and Molecular Docking Studyof <i>N</i>-Phenylpyrazoline Derivatives

Cited by 10 publications

References 27 publications

Molecular Docking Approach For Design and Synthesis of Thioxanthone Derivatives as Anticancer Agents

Molecular Docking Approach For Design and Synthesis of Thioxanthone Derivatives as Anticancer Agents

A Potent EGFR Inhibitor, N-Phenyl Pyrazoline Derivative Suppresses Aggressiveness and Cancer Stem Cell-Like Phenotype of Cervical Cancer Cells

Synthesis, characterization, molecular docking and in vitro anticancer activity of 3-(4-methoxyphenyl)-5-substituted phenyl-2-pyrazoline-1- carbothioamide

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