Design, efficient synthesis and molecular docking of some novel thiazolyl-pyrazole derivatives as anticancer agents

Sayed, Abdelwahed R.; Gomha, Sobhi M.; Abdelrazek, Fathy M.; Farghaly, Marwa; Hassan, Shaimaa; Metz, Peter

doi:10.1186/s13065-019-0632-5

Cited by 75 publications

(27 citation statements)

References 42 publications

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“…According to docking results on the EGER kinase active site, all compounds showed low binding energy from −3.4 to −1.3 kcal/mol with an order that confirms the experimental findings. Sayed et al [122] synthesized a series of novel thiazolyl-pyrazole derivatives and evaluated against the human liver carcinoma cell line (HepG-2) using MTT assay and doxorubicin as a reference drug. Among all the tested compounds, 79d, 80a, 81a, and 82 (Figure 31) exhibited good anticancer activity with IC 50 values ranging from 1.25 to 4.8 µg/mL compared to doxorubicin (IC 50 of 3.07 ± 0.27 µg/mL).…”

Section: Thiazole Derivatives As Anticancer Agentsmentioning

confidence: 99%

Thiazole Ring—A Biologically Active Scaffold

2021

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Background: Thiazole is a good pharmacophore nucleus due to its various pharmaceutical applications. Its derivatives have a wide range of biological activities such as antioxidant, analgesic, and antimicrobial including antibacterial, antifungal, antimalarial, anticancer, antiallergic, antihypertensive, anti-inflammatory, and antipsychotic. Indeed, the thiazole scaffold is contained in more than 18 FDA-approved drugs as well as in numerous experimental drugs. Objective: To summarize recent literature on the biological activities of thiazole ring-containing compounds Methods: A literature survey regarding the topics from the year 2015 up to now was carried out. Older publications were not included, since they were previously analyzed in available peer reviews. Results: Nearly 124 research articles were found, critically analyzed, and arranged regarding the synthesis and biological activities of thiazoles derivatives in the last 5 years.

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Section: Thiazole Derivatives As Anticancer Agentsmentioning

confidence: 99%

Thiazole Ring—A Biologically Active Scaffold

2021

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“…Heterocyclic scaffolds have attracted considerable attention in the design of many biologically active synthetic compounds [ 10 , 11 , 12 , 13 , 14 ]. Pyrimidine, six-membered ring heterocyclic ring with two nitrogen atoms, is widely present in several natural and synthetic drugs [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

et al. 2021

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Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

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“…The release of binding energy also compensates for any ligand transformation from its energy minimum to its bound conformation with the protein. Higher negative binding energy means better stability of the complex [32][33][34].…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Evaluation of Core Scaffold Pyrazolone Fused Thiazolidinone Derivatives as Anticancer Agents

Arunachalam¹,

Ramalingam

Lachmanan³

et al. 2021

JPRI

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Background: Cancer is the world's second leading cause of death, accounting for an estimate of more than 10 million deaths annually. The most common type of cancers in women are breast, endometrial, cervical, ovarian, colorectal, lung, and skin cancers.Among these, breast cancer is the most common in women of all ages. Human epidermal growth factor receptor 2 breast cancer is widely seen in women which test positive for the protein HER2. This protein is present in one-fifth of every breast cancer cell, which promotes the growth of cancer cells. There are several compounds available for the treatment of HER2 breast cancer in the market with varying promise in their efficacy and safety on HER2 treatment. Objective: To design synthesis and evaluation of core scaffold pyrazolone fused thiazolidinone derivatives as anticancer agents. Methods: In this study, the core scaffold pyrazolone fused thiazolidinone derivatives were designed, synthesized, and analyzed for the anticancer activity using breast carcinoma cell line (MCF-7), against the standard drug Doxorubicin. Results: Many thiazoles, fused thiazole, and pyrazole derivatives have been found to have anti-cancer and other properties. In this study, the compound 1-phenyl-3-methyl-5-pyrazolones was allowed to react with diverse benzoyl chloride as well as primary amine derivatives and transformed into ’A series of Pyrazolone fused Thiazolidinone derivatives 4A1-4A10 and 4B1- 4B10. Computational studies by Schrodinger Glide XP using the Protein 3RCD which act on the human epidermal growth factor receptor’’ was performed on the selected scheme initially and further from the docked score data the synthesis of pyrazolone fused thiazolidinone was performed. Conclusion: Among the compounds synthesized, five compounds (4A6 − 3.4 kcal/mol, 4B4 − 3.0 kcal/mol, 4A3 − 2.2 kcal/mol, 4B2 − 1.6 kcal/mol, and 4A9 − 1.3 kcal/mol) shown promising binding affinities against epidermal growth factor receptor kinase. The cytotoxic potential of the compounds was examined using a breast carcinoma cell line (MCF-7), which shown cytotoxicity close to Doxorubicin (standard drug). Our findings are an important step forward in the development of novel anticancer agents.

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Design, efficient synthesis and molecular docking of some novel thiazolyl-pyrazole derivatives as anticancer agents

Cited by 75 publications

References 42 publications

Thiazole Ring—A Biologically Active Scaffold

Thiazole Ring—A Biologically Active Scaffold

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Design, Synthesis and Evaluation of Core Scaffold Pyrazolone Fused Thiazolidinone Derivatives as Anticancer Agents

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