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

Abdelwahed R Sayed; Sobhi M Gomha; Fathy M Abdelrazek; Mohamed S Farghaly; Shaimaa A Hassan; Peter Metz

doi:10.1186/s13065-019-0632-5

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

BMC Chem. 2019 Sep 24;13(1):116. doi: 10.1186/s13065-019-0632-5. eCollection 2019 Dec.

Authors

Abdelwahed R Sayed^{1

2}, Sobhi M Gomha^{3

4}, Fathy M Abdelrazek^{3

5}, Mohamed S Farghaly^{3

5}, Shaimaa A Hassan³, Peter Metz⁶

Affiliations

¹ 1Department of Chemistry, Faculty of Science, King Faisal University, Hofuf, Saudi Arabia.
² 3Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
³ 2Chemistry Department, Faculty of Science, Cairo University, Giza, 12613 Egypt.
⁴ Department of Chemistry, Faculty of Science, Islamic University in Almadinah Almonawara, Almadinah Almonawara, 42351 Saudi Arabia.
⁵ Science and Technology Center of Excellence, Ministry of Military Production, Cairo, Egypt.
⁶ 6Fakultat Chemie und Lebensmittelchemie, TU-Dresden, 01069 Dresden, Germany.

Abstract

Pyrazoles, thiazoles and fused thiazoles have been reported to possess many biological activities. 3-Methyl-5-oxo-4-(2-arylhydrazono)-4,5-dihydro-1H-pyrazole-1-carbothioamides 3a,b (obtained from the reaction of ethyl 3-oxo-2-(2-arylhydrazono)butanoates 1a,b with thiosemicarbazide) could be transformed into a variety of thiazolyl-pyrazole derivatives 6a-h, 10a-c, 15a-c, 17, 19 and 21 via their reaction with a diversity hydrazonoyl chlorides as well as bromoacetyl derivatives. Moreover, the computational studies were carried out for all new compounds. The results indicated that five compounds showed promising binding affinities (10a: - 3.4 kcal/mol, 6d: - 3.0 kcal/mol, 15a: - 2.2 kcal/mol, 3a: - 1.6 kcal/mol, and 21: - 1.3 kcal/mol) against the active site of the epidermal growth factor receptor kinase (EGFR). The cytotoxicity of the potent products 3a, 6d, 10a, 15a, and 21 was examined against human liver carcinoma cell line (HepG-2) and revealed activities close to Doxorubicin standard drug. There was an understanding between the benefits of restricting affinities and the data obtained from the practical anticancer screening of the tested compounds.

Keywords: Anticancer activity; Coupling reaction; Cyclocondensation; Hydrazonoyl halides; Molecular docking; Pyrazolones.