Fluorinated azole anticancer drugs: Synthesis, elaborated structure elucidation and docking studies

The present article deals with the synthesis of novel nano-sized fluorinated thiazoles and studying their anticancer potentiality. The targeted azoles could be accessed via trifluoromethylated thiosemicarbazone (3) prepared by reaction of with thiosemicarbazide in acidic solution of ethanol. The latter a fluorinated building block (3) have been reacted with appropriate derivatives of a-halo compounds namely, N-aryl 2-oxopropane-hydrazonoyl chlorides 4a-f using dioxane containing TEA as base catalyst. Also, the reaction between N-(4-(1-(2-carbamothioylhydrazineyli dene)ethyl)phenyl)-2,2,2-trifluoroacetamide (3) and chloroacetonitrile 8 under the same experimental conditions furnished the corresponding amino thiazole derivative 11. In the same manner the base catalyzed cyclocondensation reaction between N-(4-(1-(2-carbamothioylhydrazineylidene)ethyl)phenyl)-2, 2,2-trifluoroacetamide (3) and phenacyl bromide derivatives 12a-d afforded the corresponding thiazoles 13a-d in good yield. The structure of all synthesized thiazole derivatives as well as their mechanistic pathways were studied based on spectral data analysis and physical characteristics. The nanosized products were confirmed by using XRD analysis. Moreover, twelve samples were submitted for evaluation of their cytotoxicity activities against MDA-MB-231 (breast cancer cell) using colorimetric MTT assay, in comparison with Cisplatin standard drug. Two nano-sized thiosemicarbazone derivative 3 and the thiazole derivative 7c showed potent activity with IC50 = 7.7 and 2.97 mg/ml, respectively in compared with the IC50 = 4.33 mg/ml of cisplatin. The nanosized thiazole derivative 7c was more potent than cisplatin. Also, two thiazole derivatives 13b and 7b showed good activity with IC50 = 13.4 and 14.9 mg/ml. In addition, the molecular docking studies have been achieved using 4hy0, (X-chromosome -linked-inhibitor of apoptosis protein; (XIAP)).(C) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

The present study synthesized novel nano-sized fluorinated thiazoles and evaluated their anticancer potential. The targeted thiazoles were synthesized and their structures and mechanistic pathways were studied based on spectral data analysis and physical characteristics. The cytotoxicity experiments revealed that the nano-sized thiazole derivative 7c exhibited stronger anticancer activity than cisplatin.