Abstract

Background: Chalcones, 2-pyrazolines and thiazoles have been reported to possess various pharmacological activities.

Objective: Synthesis of new chalcones and utilizing them as a building block for constructing a series of thiazole derivatives and evaluating some of them as anticancer agents.

Method: The new compounds were synthesized via stirring at room temperature or thermal heating. Cytotoxic evaluation of the new synthesized compounds was tested using the method of Skehan et al. Moreover, the computational studies were performed using MOE 2014.09 software.

Result: A series of new chalcones were prepared by the reaction of ethyl 3-acetyl-1-aryl-5-methyl- 1H-pyrazole-4-carboxylate with a number of substituted benzaldehydes. One of these chalcones was used as a building block for constructing a pyrazoline ring via its reaction with thiosemicarbazide. The produced carbothioamide derivative was used for the preparation of two series of thiazole derivatives by its reaction with a number of hydrazonoyl chlorides. Moreover, reaction of 3- acetylpyrazole thiosemicarbazone derivative with a number of N-aryl-2-oxopropane hydrazonoyl chlorides afforded 5-arylazothiazole derivatives. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data. Some of the newly synthesized chalcones and thiazoles were tested for their cytotoxicity against human colon carcinoma cell line (HCT-116) and the molecular docking was carried out on the most active compound 3f.

Conclusion: The results of the anticancer activity revealed that compounds 3f, 3e, 3c and 3b have promising activities compared with the standard drug Doxorubicin. Moreover, the computational studies confirm the results of biological activity. Also, the ADME profile study showed that compound 3f can be considered as a promising drug by conducting good pharmacokinetic and medicinal chemistry tests.

Keywords: ADME study, chalcones, cytotoxicity evaluation, molecular docking, pyrazolines, thiazoles, hydrazonoyl halides.

Graphical Abstract