Fluorophore-tagged pharmacophores for antitumor cytotoxicity: Modified chiral lipidic dialkynylcarbinols for cell imaging

Listunov, Dymytrii; Mazères, Serge; Volovenko, Yulian M.; Joly, Etienne; Génisson, Yves; Maraval, Valérie; Chauvin, Rémi

doi:10.1016/j.bmcl.2015.08.029

Cited by 19 publications

(21 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The target monoadducts were thus isolated in 95-97% ee (as determined by chiral SFC analysis of the 1-naphthylcarbamate derivatives). 17,35 Reaction of the TMS-protected ω-ethynyl-DAC (S)-30a with 1-(4-azidobutyl)pyrene in the presence of CuI, tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) and Et 3 N 36 proceeded selectively, delivering the in situ-protodesilylated triazole product (S)-31 in 63% yield. With other azido-fluorophores, such as the hydroxycoumarin azide 32, the in situ protodesilylated DAC terminal triple bond of 30a was found to react preferably, giving (S)-33 no longer possessing a DAC pharmacophore (Scheme 8).…”

Section: Fluorophore-labeled Lipidic Dialkynylcarbinolsmentioning

confidence: 99%

From Natural to Artificial Antitumor Lipidic Alkynylcarbinols: Asymmetric Synthesis, Enzymatic Resolution, and Refined SARs

et al. 2018

Self Cite

View full text Add to dashboard Cite

Among acetylenic natural products, chiral lipidic alkynylcarbinol (LAC) metabolites, mostly extracted from marine sponges, have revealed a broad spectrum of biological activities, in particular, remarkable antitumor cytotoxicity. With reference to one of the simplest natural representatives, [(S)-eicos-(4E)-en-1-yn-3-ol], and a given cancer cell line (HCT116), combined extensive efforts in chemical synthesis (relying on the use of a large chemical toolbox) and biological analysis (in vitro tests), have provided systematic structure–activity relationships (SARs) where the initially selected four structural parameters appear as independent principal components: (i) and (ii) the sp/sp2 content and extent of the terminal and internal unsaturations adjacent to the carbinol center, (iii) the absolute configuration of the latter, (iv) the length of the n-aliphatic backbone. Two key criteria have also been established regarding the functional alkynylcarbinol pharmacophore: the alkynylcarbinol unit must be both secondary and terminal (i.e., substituted by a short ethynyl or ethenyl C2 group). This review is intended to provide a further illustration of the value of a simple rational approach for drug design, and to act as a benchmark for future optimization of LACs as antitumor agents.1 Introduction2 2C2-Unsaturated Pharmacophore Candidates2.1 Alkenylalkynylcarbinols (AACs)2.2 Dialkynylcarbinols (DACs or DACys)2.3 Alkynylalkenylcarbinols (iso-AACs) and Dialkenylcarbinols (DACes)2.4 Oxidation-Protected Dialkynylcarbinols and Dialkynylketones2.5 Fluorophore-Labeled Lipidic Dialkynylcarbinols3 C2/C3-Unsaturated Pharmacophore Candidates3.1 Cyclopropylalkynylcarbinols (CACs)3.2 Allenylalkynylcarbinols (AllACs)4 C2/C4- and 3C2-Unsaturated Pharmacophore Candidates4.1 Butadiynylalkynylcarbinols (BACs)4.2 Trialkynylcarbinols (TACs)5 Double-AC-Headed Pharmacophore Candidates6 Screening on the Lipidic Chain Length7 Conclusion

show abstract

Section: Fluorophore-labeled Lipidic Dialkynylcarbinolsmentioning

confidence: 99%

From Natural to Artificial Antitumor Lipidic Alkynylcarbinols: Asymmetric Synthesis, Enzymatic Resolution, and Refined SARs

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Various hydrazone 34 , [1,2,4‐triazolo][3,4‐ b ]thiadiazinyl 35 , pyrazole 36 , alkyl and aryl 37 , pyridine 38 , chalcone 39 , 3‐oxo‐2,3‐dihydrofuran 40 , pyrrole , dithiocarbamate , benzimidazole , dialkynylcarbinol , steroidal , costunolide , colchicines , (−)‐Dibromophakellstatin fused coumarin–triazole hybrids and cyclized coumarin–triazole hybrids , the 1,2,4‐triazole‐5‐one hybrids 41 , as well as triazole tethered bis‐coumarin 42 (Fig. ) were screened for their anticancer activities, in spite of the majority of them showed weak to moderate activity against the tested cancer cell lines, the enriched SAR paved the way to the further rational design.…”

Section: Antitumor Activitymentioning

confidence: 99%

Coumarin–triazole Hybrids and Their Biological Activities

Fan

Xing

Liu

2018

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

Hybridization is emerged as a promising strategy in the discovery of new drugs, especially these with complimentary activities and multiple pharmacological targets that are the potential weapons to prevent the drug resistance. Currently, several hybrids are under different stages of clinical trial, and may be introduced into clinical practice to treat various diseases in the near future. Triazoles including 1,2,3‐triazole and 1,2,4‐triazole as well as coumarins occupy an important position in medicinal chemistry attribute to their various biological activities, and some of them have been used in clinical practice. Obviously, hybridization of these two pharmacophores may lead to novel candidates with broader spectrum, more effective, lower toxicity, and multiple mechanisms of action. This review aims to outline the biological activities of coumarin–triazole hybrids, and discuss their structure–activity relationship to pave the way for the further rational development of this kind of hybrids.

show abstract

“…Originally identified as natural bioactive compounds extracted from marine sponges or plant roots [1], lipidic alkynylcarbinols (LACs) constitute a class of potential antitumoral compounds [2]. Over the past few years, efforts have been devoted to the delineation of both optimal structural features [3] and cellular targets [4] of LAC derivatives exhibiting in vitro antiproliferative activity against the HCT116 colon tumor cell line. Noteworthy is a significant and systematic chirality effect, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…(t, J = 6.7 Hz, 3H). 13 C NMR (75 MHz, CDCl3) δ 204.5 (C=O), 125.7 (t, J = 245.9 Hz, CF2), 101 4,. 77.4 (dd, J = 30.4, 27.8 Hz), 60.0 (OMe), 54.2 (OMe), 53.8 (OMe), 47.4, 43.7 (dd, J = 3.8, 1.9 Hz), 32.7 (t, J = 24.1 Hz),32.0, 29.7, 29.6, 29.6, 29.5, 29.5, 22.8, 21.4 (t, J = 4.3 Hz), 14.3.…”

mentioning

confidence: 99%

Fluorinated analogues of lipidic dialkynylcarbinol pharmacophores: synthesis and cytotoxicity in HCT116 cancer cells

et al. 2019

View full text Add to dashboard Cite

Lipidic alkynylcarbinols (LACs) have been identified as potential antitumor compounds, and a thorough understanding of their pharmacophoric environment is now required to elucidate their biological mode of action. In the dialkynylcarbinol (DAC) series, a specific study of the pharmacophore potential has been undertaken by focusing on the synthesis of three fluorinated derivatives followed by their biological evaluation. This work highlights the requirement of an electron-rich secondary carbinol center as a key structure for cytotoxicity in HCT116 cells.

show abstract

Fluorophore-tagged pharmacophores for antitumor cytotoxicity: Modified chiral lipidic dialkynylcarbinols for cell imaging

Cited by 19 publications

References 24 publications

From Natural to Artificial Antitumor Lipidic Alkynylcarbinols: Asymmetric Synthesis, Enzymatic Resolution, and Refined SARs

From Natural to Artificial Antitumor Lipidic Alkynylcarbinols: Asymmetric Synthesis, Enzymatic Resolution, and Refined SARs

Coumarin–triazole Hybrids and Their Biological Activities

Fluorinated analogues of lipidic dialkynylcarbinol pharmacophores: synthesis and cytotoxicity in HCT116 cancer cells

Contact Info

Product

Resources

About