“Common synthetic scaffolds” in the synthesis of structurally diverse natural products

Anagnostaki, Elissavet E.; Zografos, Alexandros L.

doi:10.1039/c2cs35080g

Cited by 61 publications

(22 citation statements)

References 44 publications

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“…1. The total chemical synthesis of natural substances furanogermenone, zedoarol and gweicurculactone was based on the unified synthetic protocol and methods in our previously published studies (18)(19)(20)(21). All natural and synthetic substances were purified by flash column chromatography with Merck silica gel 60 (particle size, 0.040-0.063 mm; EMD Millipore, Billerica, MA, USA).…”

Section: Synthesis Of Natural Sesquiterpenoids and Analogsmentioning

confidence: 99%

Uncovering the pharmacological response of novel sesquiterpene derivatives that differentially alter gene expression and modulate the cell cycle in cancer cells

et al. 2018

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The present study aimed to assess the pharmacological anticancer profile of three natural and five synthetic sesquiterpenes developed by total chemical synthesis. To this end, their properties at the cellular and molecular level were evaluated in a panel of normal and cancer cell lines. The results obtained by performing cytotoxicity assays and gene expression analysis by reverse transcription-quantitative polymerase chain reaction showed that: i) Among the sesquiterpene derivatives analyzed, VDS58 exhibited a notable anticancer profile within attached (U-87 MG and MCF-7) and suspension (K562 and MEL-745) cancer cell cultures; however, U-87 MG cells were able to recover their proliferation capacity rapidly after 48 h of exposure; ii) gene expression profiling of U-87 MG cells, in contrast to K562 cells, showed a transient induction of cyclin-dependent kinase inhibitor 1A (CDKN1) expression; iii) the expression levels of transforming growth factor β1 (TGFB1) increased after 12 h of exposure of U-87 MG cells to VDS58 and were maintained at this level throughout the treatment period; iv) in K562 cells exposed to VDS58, TGFB1 expression levels were upregulated for 48 h and decrease afterwards; and v) the re-addition of VDS58 in U-87 MG cultures pretreated with VDS58 resulted in a notable increase in the expression of caspases (CASP3 and CASP9), BCL2‑associated agonist of cell death (BAD), cyclin D1, CDK6, CDKN1, MYC proto-oncogene bHLH transcription factor (MYC), TGFB1 and tumor suppressor protein p53. This upregulation persisted only for 24 h for the majority of genes, as afterwards, only the expression of TGFB1 and MYC was maintained at high levels. Through bioinformatic pathway analysis of RNA-Seq data of parental U-87 MG and K562 cells, substantial variation was reported in the expression profiles of the genes involved in the regulation of the cell cycle. This was associated with the differential pharmacological profiles observed in the same cells exposed to VDS58. Overall, the data presented in this study provide novel insights into the molecular mechanisms of action of sesquiterpene derivatives by dysregulating the expression levels of genes associated with the cell cycle of cancer cells.

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Section: Synthesis Of Natural Sesquiterpenoids and Analogsmentioning

confidence: 99%

Uncovering the pharmacological response of novel sesquiterpene derivatives that differentially alter gene expression and modulate the cell cycle in cancer cells

et al. 2018

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“…We also included tests against mammalian glial cells, in culture, to evaluate toxicity for another cell type. In addition to the total synthesis of natural products [29][30][31][32][33][34][35][36], there is constant demand for the synthesis of unnatural heterocycles to access novel chemical space [37][38][39][40][41][42][43][44][45]. Although not authentic derivatives of secondary metabolites, these moieties resemble inherently diverse natural products [46][47][48][49][50][51][52].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Polycyclic Ether-Benzopyrans and In Vitro Inhibitory Activity against Leishmania tarentolae

et al. 2020

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Construction of a focused library of polycyclic ether-benzopyrans was undertaken in order to discover new therapeutic compounds that affect Leishmania growth and infectivity. This is especially of interest since there are few drug therapies for leishmaniasis that do not have serious drawbacks such high cost, side effects, and emerging drug resistance. The construction of these polycyclic ether-benzopyrans utilized an acetoxypyranone-alkene [5+2] cycloaddition and the Suzuki-Miyaura cross-coupling. The multi-gram quantity of the requisite aryl bromide was obtained followed by effective Pd-catalyzed coupling with boronic acid derivatives. Compounds were tested in vitro using the parasitic protozoan, Leishmania tarentolae. Effects of concentration, time, and exposure to light were evaluated. In addition, the effects on secreted acid phosphatase activity and nitric oxide production were investigated, since both have been implicated in parasite infectivity. The data presented herein are indicative of disruption of the Leishmania tarentolae and thus provide impetus for the development and testing of a more extensive library.

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“…Over the last 30 years, this concept has led to remarkable unified strategies for the syntheses of various families of natural products. 3 Here, we present the extension of this idea to the syntheses of congeners in the prenylated indole alkaloid family which features a powerful Dieckmann-type cyclization to forge a key [2.2.2]bicycle.…”

Section: Introductionmentioning

confidence: 99%

Unified approach to prenylated indole alkaloids: total syntheses of (−)-17-hydroxy-citrinalin B, (+)-stephacidin A, and (+)-notoamide I

Mercado-Marin

Sarpong

2015

Chem. Sci.

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“Common synthetic scaffolds” in the synthesis of structurally diverse natural products

Cited by 61 publications

References 44 publications

Uncovering the pharmacological response of novel sesquiterpene derivatives that differentially alter gene expression and modulate the cell cycle in cancer cells

Uncovering the pharmacological response of novel sesquiterpene derivatives that differentially alter gene expression and modulate the cell cycle in cancer cells

Synthesis of Polycyclic Ether-Benzopyrans and In Vitro Inhibitory Activity against Leishmania tarentolae

Unified approach to prenylated indole alkaloids: total syntheses of (−)-17-hydroxy-citrinalin B, (+)-stephacidin A, and (+)-notoamide I

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