Synthesis of Functionalized 1‐Aryl‐3‐phenylthiazolylpropanoids and Their Potential as Anticancer Agents

Abstract

Natural products have inspired the development of multipletarget anticancer agents. To reach this goal, preparation of hybrid molecules was adopted as a recent approach to target and affect both sensitive and resistant cells. In the continuation of the search for potent anticancer agents, nine thiazole-based chalcones were prepared. Their cytotoxic activities were evaluated against twenty cancer cell lines and against the normal cell line AML12 hepatocytes. The key steps of these syntheses involved Hantzsch, Sommelet, and Claisen-Schmidt reactions. Julia-Colonna reaction was used to achieve the epoxidation of the double bond. The products were purified by chromatographic techniques and were characterized by spectroscopic methods. Cytotoxicity assays were performed by rezasurin reduction test. Compounds 4-10 showed promising cytotoxic activities. 4 and 7 were the most cytotoxic with IC 50 values lower than 1 μM against seven and two cancer cell lines, respectively. This study disclosed a new series of potential anticancer agents among which 4 and 7 deserve further investigation to develop drug for sensitive and multidrug resistant (MDR) cancer.

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“…A better yield was obtained when the cyclisation was performed in the presence of sodium acetate in methanol [44].…”

“…Synthesis of 3-indolyl-1-pyridyl-2-propenones with anticancer properties [54] Concerning the antiproliferative activity of the thiazole aurones resulted from the oxidative cyclisation of the corresponding ortho-hydroxychalcones, the best results were observed for compounds 13 and 14 (Table I, lines 13 and 14) which displayed good cytotoxic activity against the leukemia cell lines CEM/ADR5000 and against the breast cancer cell lines MDA-MB231/ BCRP (Table I, lines 13 and 14) [43]. Thiazole methoxychalcones 20 and 21, obtained by Claisen-Schmidt condensation of 2-phenylthiazole carbaldehyde with 2-methoxyacetophenone and respectively 2,4-dimethoxyacetophenone [44], showed good anticancer activity with IC 50 values below 1 μM against several cancer cell lines such as human leukaemia, human colon carcinoma, glioblastoma and cervical cancer cells. The antiproliferative effect of the two compounds against these cancer cell lines proved to be superior to doxorubicin, which was the reference drug used in the experiments (Table I, lines 15 and 16) [44].…”

“…The chemical behaviour of 2-phenylthiazole orthomethoxychalcones in cyclisation reactions was studied in order to obtain new epoxydes and flavones (Figure 24) [44]. In the synthesis of epoxydes, it was confirmed that the methoxyl group grafted on the benzoyl moiety is resistant in the presence of hydrogen peroxide and NaOH.…”

“…In the synthesis of epoxydes, it was confirmed that the methoxyl group grafted on the benzoyl moiety is resistant in the presence of hydrogen peroxide and NaOH. By reflux with iodine in dimethylsulfoxyde, the ortho-methoxy-chalcones were cyclised to the corresponding flavones, this step involving the demethylation of the methoxyl group from the benzoyl moiety of chalcone [44].…”

“…Thiazole methoxychalcones 20 and 21, obtained by Claisen-Schmidt condensation of 2-phenylthiazole carbaldehyde with 2-methoxyacetophenone and respectively 2,4-dimethoxyacetophenone [44], showed good anticancer activity with IC 50 values below 1 μM against several cancer cell lines such as human leukaemia, human colon carcinoma, glioblastoma and cervical cancer cells. The antiproliferative effect of the two compounds against these cancer cell lines proved to be superior to doxorubicin, which was the reference drug used in the experiments (Table I, lines 15 and 16) [44]. Since the biological activity could be generally influenced by the lipophilicity of bioactive compounds, we considered necessary to also discuss the results regarding the lipophilicity evaluation of some of the previously synthesized thiazole chalcones and aurones with antitumor properties.…”