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

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.

Green Synthesis and Molecular Docking of Thiazolyl-thiazole Derivatives as Potential Cytotoxic Agents.

METHOD: A series of novel thiazole derivatives were synthesized in a good yield via reaction of 2-(1-(4-methyl-2-phenylthiazol-5-yl)ethylidene)hydrazine carbothioamide with hydrazonoyl halides. The reaction was performed in the presence of DABCO as an organocatalyst in short reaction times, easy workup, good to excellent yields. The structure of the newly synthesized products was elucidated via elemental analysis, spectral data and alternative routes whenever possible. Ten compounds were evaluated for their anti-cancer activity against the colon carcinoma cell line (HCT-116). RESULTS & CONCLUSION: The results revealed that most of the tested compounds showed high or moderate anti-cancer activity. The molecular docking of five novel thiazolyl-thiazole derivatives was performed by the Molecular Operating Environment (MOE) program.

Synthesis, biological evaluation, and molecular docking studies of new pyrazol-3-one derivatives with aromatase inhibition activities.

A new series derived from 4-(2-chloroacetyl)-1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one was synthesized, characterized and its pharmacological activity toward aromatase enzyme inhibition was screened and compared to the reference native ligand letrozole. The most active compound of the series was 16, showing IC50 value of 0.0023 ± 0.0002 µm compared to letrozole with IC50 of 0.0028 ± 0.0006 µm. In addition, compounds 26 and 36 exhibit good inhibition activities close to letrozole with IC50 values 0.0033 ± 0.0001 and 0.0032 ± 0.0003 µm, respectively. Moreover, molecular docking studies were conducted to support the findings.