Stereoselective Synthesis and Cytoselective Toxicity of Monoterpene-Fused 2-Imino-1,3-thiazines

Szakonyi, Zsolt; Zupkó, István; Sillanpää, Reijo; Fülöp, Ferenc

doi:10.3390/molecules191015918

Cited by 16 publications

(20 citation statements)

References 40 publications

(50 reference statements)

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“…The intermediate thiourea adducts 15-17 were prepared in good to excellent yields [33] by the reaction of the appropriate aryl isothiocyanates or ethyl isothiocyanate and 1,3-aminoalcohols 9-11. Methyl iodide treatment of thioureas 15-17 gave thioether intermediates.…”

Section: Synthesis Of 2-imino-13-oxazine Derivativesmentioning

confidence: 99%

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Stereoselective Synthesis and Antiproliferative Activity of Monoterpene-Fused 2- Imino-1,3-oxazines

Szakonyi

Zupkó

Fueloep

2017

COS

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Background: In the recent years the 2-imino-1,3-thiazine and 2-iminothiazolidine ring systems can be found as moieties in biologically relevant compounds, including BACE1 inhibitors, or cannabinoid receptor agonists, while monoterpene-based 2-imino-1,3-thiazines, prepared from chiral 1,3-amino alcohols exhibiting pronounced antiproliferative activity. Methods:The antiproliferative activities of the prepared compounds were determined in vitro against a panel of human adherent cancer cell lines including HeLa, MCF7 and A431 by MTT assay. Results:Starting from pinane-, apopinane-and carane-based -amino acid derivatives, 1,3-amino alcohols were prepared via two-step syntheses. The reactions of the product 1,3-amino alcohols and aryl isothiocyanates yielded -hydroxythioureas, which were transformed to monoterpene-fused 2-imino-1,3-oxazines via base-catalysed ring closure. The antiproliferative activities of these 2-imino-1,3-oxazines were examined and the structure-activity relationships were studied from the aspects of the type and stereochemistry of the monoterpene ring and the substituent effects on the 1,3-oxazine ring system. The N-unsubstituted monoterpene-based derivatives exhibited considerable antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF7 and A431). Conclusions:A mild and efficient method has been developed for the synthesis of 2-imino-1,3-oxazines by the ring closure of thiourea adducts of 1,3-amino alcohols. The resulting 1,3-oxazines exert marked antiproliferative action on a panel of human cancer cell lines.

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Section: Synthesis Of 2-imino-13-oxazine Derivativesmentioning

confidence: 99%

“…Compounds 3-8 and thioureas 15a, 15c-e, 16a, 23 and 27-29 were prepared according to literature methods [15,16,28,33,37,38]; all spectroscopic data and physical properties were similar to those reported previously.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Synthesis and Antiproliferative Activity of Monoterpene-Fused 2- Imino-1,3-oxazines

Szakonyi

Zupkó

Fueloep

2017

COS

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“…1,3-Thiazine derivatives are class of compounds with potential biological activity, such as growth promoting activities [1], anti-fungal activity [2], antiproliferative [3], anti-tumor activity [4], anticancer [5], analgesic activity [6,7], calming activity [8], anticonvulsant activity [9], antibiotic alctivity [10,11], anti-inflammatory [11,12], antimicrobial [13], antimycobacterial [14], antibacterial [15] and antihypertesive [7,16]. On the other hand, pyrimidine derivatives are known to be biologically active compounds and have shown wide range of biological activities like antitubercular [17], antimicrobial, antioxidant and anti-inflammatory [18][19][20], anticancer [21], analgesic, anti-fungal activity, anti-leishmanial, antiviral activity [22,23].…”

Section: Introductionmentioning

confidence: 99%

Novel synthesis, ring transformation and anticancer activity of 1,3-thiazine, pyrimidine and triazolo[1,5-a]pyrimidine derivatives

El‐Sayed¹,

El‐Hashash²,

Ahmed³

2018

Bull. Chem. Soc. Eth.

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Synthesis, heterocyclization and anticancer activity of a new series of heterocyclic compounds are described. Aminothiazine 1 was obtained from the base induced condensation of thiourea, benzaldehyde and ethyl cyanoacetate. The synthesis of N-phenyl amino pyrimidine derivative 2 was obtained as a result of reaction of aniline with compound 1. Compound 2 underwent ring opening and recyclization upon reaction with HCl or H2O2/ NaOH to afford the acid derivative 3 or oxazine 4, respectively. Thiazine 1 undergoes ring transformation upon the effect of NH2OH.HCl to produce pyrimidine derivative 5. Heterocyclization of compound 1 with thiosemicarbazide followed by oxidation with I2/AcOH afforded triazolopyrimidine 6 and 7, respectively. Alkylation of compound 1 was promoted by reaction of 1 with ethyl iodide to give alkylated thiazine 8 which in turn undergo ring transformation when subjected to reaction with hydrazine hydrate to give pyrazole derivative 9. Refluxing of amino-1,3-thiazine derivative 1 with ethyl bromoacetate in the presence of Et3N produce the alkylated pyrimidine product 10. Hydrazonolysis of 1,3-thiazine 1 with hydrazine or phenyhydrazine gave pyrimidine derivatives 11a,b, respectively. Compound 11b was cyclized with carbon disulfide or formaldehyde to produce triazolopyrimidines 12 and 13, respectively. Some of the new compounds were screened for anticancer activity and significant results were found for some compounds.

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“…In particular, the 1,3‐thiazines have been given considerable interest in pharmaceutical research as anti‐inflammatory , antitumor , antibacterial , and antiviral agents . However, only a few studies exploring their anticancer potential have been reported . Moreover, in recent years, attention has been increasingly paid to the synthesis of bis ‐heterocyclic compounds, which exhibit various biological activities .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Anticancer Evaluation of Symmetrically Bridged 1,3‐thiazine Derivatives

Malah

Ishak

Nour

et al. 2018

Journal of Heterocyclic Chem

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A series of bis‐1,3‐thiazine derivatives 3a–o were synthesized from the condensation reactions of symmetric dialdehydes 1a–c possessing aliphatic ether spacer units with 3‐substituted‐amino‐2‐cyano‐3‐mercaptoacrylamides 2a–e. The chemical structures of the products were fully characterized by using different spectroscopic techniques, such as 1H NMR, 13C NMR, IR, electron impact mass spectrometry, and elemental analysis. Compounds 3a, 3f, and 3k underwent ring opening followed by recyclization and alkylation in basic medium to afford bis‐pyrimidinones 4a–c and 5a–c. The anticancer potential of the new bis‐1,3‐thiazines was assessed in vitro against six different human cell lines, including lung A549, colon HCT116, breast MCF‐7, prostate PC3, liver HepG2, and normal melanocyte HFB4. The results revealed a potent activity of compounds 3e and 3k against breast and liver cancer cell lines in comparison with the reference drug doxorubicin with no noticeable toxicity on normal cells.

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Stereoselective Synthesis and Cytoselective Toxicity of Monoterpene-Fused 2-Imino-1,3-thiazines

Cited by 16 publications

References 40 publications

Stereoselective Synthesis and Antiproliferative Activity of Monoterpene-Fused 2- Imino-1,3-oxazines

Stereoselective Synthesis and Antiproliferative Activity of Monoterpene-Fused 2- Imino-1,3-oxazines

Novel synthesis, ring transformation and anticancer activity of 1,3-thiazine, pyrimidine and triazolo[1,5-a]pyrimidine derivatives

Synthesis and In Vitro Anticancer Evaluation of Symmetrically Bridged 1,3‐thiazine Derivatives

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