Synthesis and in vitro antitumour screening of 2-(β-d-xylofuranosyl)thiazole-4-carboxamide and two novel tiazofurin analogues with substituted tetrahydrofurodioxol moiety as a sugar mimic
“…In fact, although it is the first time that the alkylation of the non-anomeric position of the acyl oxonium is reported for C 2 -methylated pentoses, this phenomenon has already been described during the reaction of silyl enol ethers with peracylated- D -ribofuranose catalyzed by stannic chloride to produce C -nucleosides ( Yokoyama et al, 1982 ; Berber et al, 2001 ). Since then, a few other studies have reported this generally unexpected reactivity in C 2 -acylated sugars for other C -nucleophiles, such as allenyltributylstannane ( Chan et al, 2005 ), indium acetylenides ( Lubin-Germain et al, 2008 ), trimethylaluminum ( More and Campbell, 2009 ), cyanotrimethylsilane ( Popsavin et al, 2012 ), or zinc acetylenides ( Lemaire et al, 2014 ), suggesting that the small size of the nucleophile is the most decisive factor for the observed regioselectivity. The formation of the corresponding orthoesters is well known in the field of O -glycosylation, the latter serving as intermediates in the synthesis of oligosaccharides ( Kong, 2007 ).…”
A short 3-step synthesis of the antiviral agent 7DMA is described herein. The nature of a major by-product formed during the key N-glycosylation of 6-chloro-7-deaza-7-iodopurine with perbenzoylated 2-methyl-ribose under Vorbrüggen conditions was also investigated. Spectroscopic analyses support that the solvent itself is converted into a nucleophilic species competing with the nucleobase and further reacting with the activated riboside in an unanticipated fashion. These findings call for a revision of reaction conditions when working with weakly reactive nucleobases in the presence of Lewis acids. 7DMA thus obtained was evaluated for its efficacy against an emerging flavivirus in vitro.
“…In fact, although it is the first time that the alkylation of the non-anomeric position of the acyl oxonium is reported for C 2 -methylated pentoses, this phenomenon has already been described during the reaction of silyl enol ethers with peracylated- D -ribofuranose catalyzed by stannic chloride to produce C -nucleosides ( Yokoyama et al, 1982 ; Berber et al, 2001 ). Since then, a few other studies have reported this generally unexpected reactivity in C 2 -acylated sugars for other C -nucleophiles, such as allenyltributylstannane ( Chan et al, 2005 ), indium acetylenides ( Lubin-Germain et al, 2008 ), trimethylaluminum ( More and Campbell, 2009 ), cyanotrimethylsilane ( Popsavin et al, 2012 ), or zinc acetylenides ( Lemaire et al, 2014 ), suggesting that the small size of the nucleophile is the most decisive factor for the observed regioselectivity. The formation of the corresponding orthoesters is well known in the field of O -glycosylation, the latter serving as intermediates in the synthesis of oligosaccharides ( Kong, 2007 ).…”
A short 3-step synthesis of the antiviral agent 7DMA is described herein. The nature of a major by-product formed during the key N-glycosylation of 6-chloro-7-deaza-7-iodopurine with perbenzoylated 2-methyl-ribose under Vorbrüggen conditions was also investigated. Spectroscopic analyses support that the solvent itself is converted into a nucleophilic species competing with the nucleobase and further reacting with the activated riboside in an unanticipated fashion. These findings call for a revision of reaction conditions when working with weakly reactive nucleobases in the presence of Lewis acids. 7DMA thus obtained was evaluated for its efficacy against an emerging flavivirus in vitro.
“…Through the literary survey it became clear to us that many thiazole derivatives have an excellent anti-tumor activity as shown in Fig. 1 [22, 23]. In light of this, anti-tumor activity was examined for a new series of thiazole substitutes against breast cancer cells line (MCF-7).Fig.…”
Background
Thiazole is a core structural motif presents in a wide range of natural products. Thiazole derivatives also have a wide range of medicinal and biological properties.
Results
The reaction of hydrazonoyl halides with 2-(1-(4-(1,3-dioxoisoindolin-2-yl)phenyl)ethylidene)hydrazinecarbothioamidein ethanol and triethylamine yielded 2-(4-(1-(2-(4-(2-Arylhydrazono)-5-s-4,5-dihydrothiazol-2-yl)hydrazono)-ethyl)phenyl)isoindoline-1,3-dione and 2-(4-(1-(2-(5-(2-Arylhydrazono)-4-oxo-4,5-dihydrothiazol-2-yl)hydrazono)ethyl)-phenyl)isoindoline-1,3-dione.The reaction of 2-(4-(1-(2-(4-oxo-4,5-dihydrothiazol-2-yl)hydrazono)ethyl)phenyl)isoindoline-1,3-dione with arylidenemalononitrile also yielded 5-amino-2-(2-(1-(4-(1,3-dioxoisoindolin-2-yl)phenyl)ethylidene)hydrazinyl)-7-substituted-7
H
-pyrano[2,3-
d
]thiazole-6-carbonitrile. The structures of the newly synthesized compound were elucidated whenever possible on the basis of elemental analysis, spectral data, and alternative synthetic routes. Three of them were evaluated against a breast cancer cell line for their antitumor activity.
Conclusions
Compound
(1)
has been shown to be useful in the synthesis of a new series of 1,3-thiazole, pyrano[2,3-
d
]thiazole and 4,5-dihydrothiazolo[4,5-
b
]pyridine derivatives using hydrazonoyl halides as precursors. The anticancer efficacy of compounds
(9b)
,
(9e)
, and
(9f)
against MCF-7, a breast cancer cell line, was also compared to the standard anticancer drug doxorubicin.
Electronic supplementary material
The online version of this article (10.1186/s13065-019-0559-x) contains supplementary material, which is available to authorized users.
“…Our literature survey showed that many thiazole and 1,3,4-thiadiazole derivatives have antitumor activity with excellent IG 50 and IC 50 values, as depicted in Figure 1 [55,56,57,58]. In view of these facts, we examined the antitumor activity of a new series of substituted thiadiazoles and thiazoles against the human breast carcinoma cell line (MCF-7) and against the human hepatocellular carcinoma (HepG2).…”
Abstract:Reactions of hydrazonoyl halides and each of methyl 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbodithioate and 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbothioamide afforded 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-3-phenyl-5-substituted-2,3-dihydro-1,3,4-thiadiazoles and 5-(4-substituted)diazenyl)-2-(2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-4-arylthiazoles, respectively. Analogously, the reactions of hydrazonoyl halides with 7-1H)-ones in a good yield. The structures of the newly synthesized were elucidated via elemental analysis, spectral data and alternative synthesis routes whenever possible. Twelve of the newly synthesized compounds have been evaluated for their antitumor activity against human breast carcinoma (MCF-7) and human hepatocellular carcinoma (HepG2) cell lines. Their structure activity relationships (SAR) were also studied. The 1,3,4-thiadiazole derivative 9b (IC50 = 2.94 µM) has promising antitumor activity against the human hepatocellular carcinoma cell line and the thiazole derivative 12a has promising inhibitory activity against both the human hepatocellular carcinoma cell line and the breast carcinoma cell line (IC50 = 1.19, and 3.4 µM, respectively).
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