3,4-Disubstituted oxazolidin-2-ones as constrained ceramide analogs with anticancer activities

Singh, Alok Kumar; Ha, Hyun‐Joon; Park, Jungchan; Kim, Jun Hee; Lee, Won Koo

doi:10.1016/j.bmc.2011.09.022

Cited by 27 publications

(7 citation statements)

References 51 publications

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“…During the last decades, many studies highlighted the ability of oxazolidinones to exert multifaceted biological activities, since they are able to interfere with factor Xa [10] aldose reductase [11], HIV [12], metabotropic [13], and glutamate receptor [14]. Furthermore, some derivatives exhibited antidiabetic [15,16], anticonvulsant [17], and anticancer activity [18][19][20][21]. Moreover, further literature data indicate that different oxazolidinone derivatives are endowed with promising antineoplastic activity, in particular by acting as partial agonists of peroxisome proliferator-activated receptor-gamma (PPAR-γ) [22].…”

Section: Introductionmentioning

confidence: 99%

5-(Carbamoylmethylene)-oxazolidin-2-ones as a Promising Class of Heterocycles Inducing Apoptosis Triggered by Increased ROS Levels and Mitochondrial Dysfunction in Breast and Cervical Cancer

et al. 2020

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Oxazolidinones are antibiotics that inhibit protein synthesis by binding the 50S ribosomal subunit. Recently, numerous worldwide researches focused on their properties and possible involvement in cancer therapy have been conducted. Here, we evaluated in vitro the antiproliferative activity of some 5-(carbamoylmethylene)-oxazolidin-2-ones on MCF-7 and HeLa cells. The tested compounds displayed a wide range of cytotoxicity on these cancer cell lines, measured by MTT assay, exhibiting no cytotoxicity on non-tumorigenic MCF-10A cells. Among the nine tested derivatives, four displayed a good anticancer potential. Remarkably, OI compound showed IC50 values of 17.66 and 31.10 µM for MCF-7 and HeLa cancer cells, respectively. Furthermore, we assessed OI effect on the cell cycle by FACS analysis, highlighting a G1 phase arrest after 72 h, supported by a low expression level of Cyclin D1 protein. Moreover, mitochondrial membrane potential was reduced after OI treatment driven by high levels of ROS. These findings demonstrate that OI treatment can inhibit MCF-7 and HeLa cell proliferation and induce apoptosis by caspase-9 activation and cytochrome c release in the cytosol. Hence, 5-(carbamoylmethylene)-oxazolidin-2-ones have a promising anticancer activity, in particular, OI derivative could represent a good candidate for in vivo further studies and potential clinical use.

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Section: Introductionmentioning

confidence: 99%

5-(Carbamoylmethylene)-oxazolidin-2-ones as a Promising Class of Heterocycles Inducing Apoptosis Triggered by Increased ROS Levels and Mitochondrial Dysfunction in Breast and Cervical Cancer

et al. 2020

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“…Ceramide and other sphingolipids are mainly localized in cell membranes and are involved in important cell processes. A series of constrained analogues of ceramide (2 S ,3 R )- 96 modified by converting the terminal aminohydroxy fragment into oxazolidin-2-one and acylation of the nitrogen atom with 13 selected acyl chlorides was synthesized starting from the aziridine ketone (2 S ,1' R )- 97 (Scheme 25) [76]. To introduce the R absolute configuration at C3 (ceramide numbering) the aziridine alcohol (2 S ,1' R ,1'' R )- 98 was stereoselectively obtained by reduction of the corresponding ketone with a NaBH 4 /ZnCl 2 mixture.…”

Section: Reviewmentioning

confidence: 99%

“…Catalytic ruthenium tetroxide oxidation of ( R )- 118 followed by hydrolysis gave ᴅ-phenylalanine ( R )- 116 as the hydrochloride salt [83]. Other α-amino acids of general formula RCH 2 CH(NH 2 )COOH, e.g., R = Me, iPr, PhCH 2 , were prepared in a similar way [76].…”

Section: Reviewmentioning

confidence: 99%

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

Głowacka¹,

Trocha²,

Wróblewski³

et al. 2019

Beilstein J. Org. Chem.

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Since Garner’s aldehyde has several drawbacks, first of all is prone to racemization, alternative three-carbon chirons would be of great value in enantioselective syntheses of natural compounds and/or drugs. This review article summarizes applications of N-(1-phenylethyl)aziridine-2-carboxylates, -carbaldehydes and -methanols in syntheses of approved drugs and potential medications as well as of natural products mostly alkaloids but also sphingoids and ceramides and their 1- and 3-deoxy analogues and several hydroxy amino acids and their precursors. Designed strategies provided new procedures to several drugs and alternative approaches to natural products and proved efficiency of a 2-substituted N-(1-phenylethyl)aziridine framework as chiron bearing a chiral auxiliary.

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“…Recently, oxazolidinones were developed as a new class of antibacterial drug against MRSA (methicillin-resistant staphylococcus aureus), and VRE (vancomycin-resistant enterococcus) [ 22 ]. Furthermore, it has been reported that some of the oxazolidinones showed anticancer activity and were in early clinical trials [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. The aforementioned findings indicate that the introduction of an oxazolidinone moiety to the skeleton of DHAA may produce novel derivatives with significant anticancer properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Novel Dehydroabietic Acid-Oxazolidinone Hybrids for Antitumor Properties

Wang

Pang

Huang

et al. 2018

IJMS

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Novel representatives of the important group of biologically-active, dehydroabietic acid-bearing oxazolidinone moiety were synthesized to explore more efficacious and less toxic antitumor agents. Structures of all the newly target molecules were confirmed by IR, 1H-NMR, 13C-NMR, and HR-MS. The inhibitory activities of these compounds against different human cancer cell lines (MGC-803, CNE-2, SK-OV-3, NCI-H460) and human normal liver cell line LO2 were evaluated and compared with the commercial anticancer drug cisplatin, using standard MTT (methyl thiazolytetrazolium) assay in vitro. The pharmacological screening results revealed that most of the hybrids showed significantly improved antiproliferative activities over dehydroabietic acid and that some displayed better inhibitory activities compared to cisplatin. In particular, compound 4j exhibited promising cytotoxicity with IC50 values ranging from 3.82 to 17.76 µM against all the test cell lines and displayed very weak cytotoxicity (IC50 > 100 µM) on normal cells, showing good selectivity between normal and malignant cells. Furthermore, the action mechanism of the representative compound 4j was preliminarily investigated by Annexin-V/PI dual staining, Hoechst 33258 staining, which indicated that the compound can induce cell apoptosis in MGC-803 cells in a dose-dependent manner and arrest the cell cycle in G1 phase. Therefore, 4j may be further exploited as a novel pharmacophore model for the development of anticancer agents.

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3,4-Disubstituted oxazolidin-2-ones as constrained ceramide analogs with anticancer activities

Cited by 27 publications

References 51 publications

5-(Carbamoylmethylene)-oxazolidin-2-ones as a Promising Class of Heterocycles Inducing Apoptosis Triggered by Increased ROS Levels and Mitochondrial Dysfunction in Breast and Cervical Cancer

5-(Carbamoylmethylene)-oxazolidin-2-ones as a Promising Class of Heterocycles Inducing Apoptosis Triggered by Increased ROS Levels and Mitochondrial Dysfunction in Breast and Cervical Cancer

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

Synthesis and Biological Evaluation of Novel Dehydroabietic Acid-Oxazolidinone Hybrids for Antitumor Properties

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