Synthesis, Antifungal and Antitumor Activity of Novel (Z)-5-Hetarylmethylidene-1,3-thiazol-4-ones and (Z)-5-Ethylidene-1,3-thiazol-4-ones

Alberto Insuasty,Carlos Echeverry,Marcela Raimondi,Susana Zacchino,Justo Cobo,Rodrigo Abonia,Jairo Quiroga,María Rodríguez,Juan Ramírez,Braulio Insuasty,Manuel Nogueras

doi:10.3390/molecules18055482

Alberto Insuasty, Carlos Echeverry + Show 9 more

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https://doi.org/10.3390/molecules18055482

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Abstract

New hetaryl- and alkylidenerhodanine derivatives 3a–d, 3e, and 4a–d were prepared from heterocyclic aldehydes 1a–d or acetaldehyde 1e. The treatment of several rhodanine derivatives 3a–d and 3e with piperidine or morpholine in THF under reflux, afforded (Z)-5-(hetarylmethylidene)-2-(piperidin-1-yl)thiazol-4(5H)-ones and 2-morpholinothiazol-4(5H)-ones 5a–d, 6a–d, and (Z)-5-ethylidene-2-morpholinothiazol-4(5H)-one (5e), respectively, in good yields. Structures of all compounds were determined by IR, 1D and 2D NMR and mass spectrometry. Several of these compounds were screened by the U.S. National Cancer Institute (NCI) to assess their antitumor activity against 60 different human tumor cell lines. Compound 3c showed high activity against HOP-92 (Non-Small Cell Lung Cancer), which was the most sensitive cell line, with GI50 = 0.62 μM and LC50 > 100 μM from the in vitro assays. In vitro antifungal activity of these compounds was also determined against 10 fungal strains. Compound 3e showed activity against all fungal strains tested, but showed high activity against Saccharomyces cerevisiae (MIC 3.9 μg/mL).

Highlights

In recent years, the synthesis and pharmacological properties of several rhodanine derivatives have been reported [1,2]
New rhodanine derivatives were prepared from heterocyclic aldehydes 1a–d by different pathways, leading to the hetarylmethylidenerhodanine 3a–d and the rhodanine-3-acetic acid derivatives 4a–d
New hetaryl- and alkylidenerhodanine derivatives 3a–e, and 4a–d, 5a–d and 6a–d were prepared from heterocyclic aldehydes 1a–d or acetaldehyde 1e

Summary

Introduction

The synthesis and pharmacological properties of several rhodanine derivatives have been reported [1,2]. The substitution of rhodanine derivatives at C-2 (C=S) of the ring has produced compounds with important biological activity [7]. This type of compounds has been used as precursors for the synthesis of new fused heterocyclic systems [8]. New hetarylmethylidene derivatives were synthesized by Xu and co-workers [9] from the reaction of 1,3-diarylpyrazole-4-carbaldehyde with rhodanine-3-acetic acid. We report the synthesis of some new hetarylmethylidene rhodanine derivatives and their antitumor and antifungal activities

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