Synthesis of C-1 homologues of pancratistatin and their preliminary biological evaluation

Vshyvenko, Sergey; Scattolon, Jon; Hudlický, Tomáš; Romero, Arthur G.; Kornienko, Alexander

doi:10.1016/j.bmcl.2011.06.068

Cited by 33 publications

(33 citation statements)

References 31 publications

(20 reference statements)

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“…The dihydrobenzodioxine ring was formed with 1,2-dibromoethane in DMF, in the presence of K 2 CO 3 [44] to afford 2,3-dihydrobenzo[b] [1,4]dioxine-6-carbaldehyde (16) and 8-methoxy-2,3-dihydrobenzo[b] [1,4]dioxine-6-carbaldehyde (17) in good yield (63%). In the next step, acetone was condensed with these benzaldehyde derivatives 16 and 17 in the Claisen-Schmidt reaction applying a high excess of acetone in water and basic conditions (NaOH) to give 4-(2,3-dihydrobenzo[b] [1,4]dioxin-6-yl)but-3-en-2-one (18) and 4-(8-methoxy-2,3-dihydrobenzo[b] [1,4]dioxin-6yl)but-3-en-2-one (19) in good yields (83 and 62%, respectively). Since dibenzylidene acetone derivatives may also be formed during this reaction, the pure products were obtained after distillation.…”

Section: Resultsmentioning

confidence: 99%

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Stereoselective synthesis of trans-dihydronarciclasine derivatives containing a 1,4-benzodioxane moiety

et al. 2018

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Some new trans-dihydronarciclasine derivatives containing a 1,4-benzodioxane moiety were stereoselectively synthesised using our feasible and efficient method developed recently. These new phenanthridone alkaloid analogues were obtained in both racemic and optically active forms. High enantioselectivities (up to 99% ee) were achieved by applying (8S,9S)-9amino(9-deoxy)epiquinine as an organocatalyst. Due to a side reaction, various methoxyphenanthridine regioisomers were also prepared which afforded further synthetic trans-dihydronarciclasine analogues modified in the ring A of the phenanthridone scaffold. Graphical abstract

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Section: Resultsmentioning

confidence: 99%

“…1) [6]. Further structure-activity relationship studies have intensively been made to find more effective synthetic analogues, but the modifications rather touched the ring C of the phenanthridone skeleton [7][8][9][10][11][12][13][14][15][16][17][18][19][20] than its ring A [21][22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Stereoselective synthesis of trans-dihydronarciclasine derivatives containing a 1,4-benzodioxane moiety

et al. 2018

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“…39 The intensive research work has been done in the searching of higher anti-cancer pancratistatin derivatives (Fig. 40 Removal of another oxygen in ring A of pancratistatin further lowers the potency 10 times relative to 7-deoxypancratistatin and 100 times relative to pancratistatin. The pancratistatin's SAR data indicate that the presence of large hydrophobic C-1 substituents can increase anticancer activities, and the 7-hydroxy group is an important part of the cytotoxic pharmacophore as well as the full amino inositol motif (Table 6).…”

Section: Anticancer Activitiesmentioning

confidence: 99%

Biological and pharmacological activities of amaryllidaceae alkaloids

et al. 2015

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The amaryllidaceae family consists of about 75 genera and 1100 species that are wide-spread in the tropics and warm temperate regions of the world. Since the first isolation of lycorine, more than 500 amaryllidaceae alkaloids have been isolated over the past three decades. The enormous numbers of diverse amaryllidaceae alkaloids are classified into different groups mainly according to their structural features. The representative alkaloids are norbelladine, lycorine, hippeastrine, narwedine, haemanthamine, pancratistatin, pretazettine, montanine, galanthindole, cherylline and ismine. Recently, more extensive studies have revealed that amaryllidaceae alkaloids exhibit a wide range of bioactivities, such as antitumor, antiviral, antibacterial, antifungal, antimalarial and analgesic. Acetylcholinesterase (AChE) inhibitory and cytotoxic activities have also been reported. The aim of the present review is to discuss the recent developments on the biological and pharmacological activities of amaryllidaceae alkaloids with IC 50 or EC 50 values since 2005, supporting the potential therapeutic possibilities for the use of these compounds.

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“…Cells were grown to 60 to 70% confluence before being treated with SVTH-6, PL (P-004; Indofine Chemical, Hillsborough Township, NJ, USA), and NAC (A7250; Sigma-Aldrich) at the indicated concentrations and time points. SVTH-6, a C-1 acetoxymethyl analog of PST, was produced by synthesis from bromobenzene (26). NAC was dissolved in sterile water.…”

Section: Cell Treatmentmentioning

confidence: 99%

Exploiting mitochondrial and oxidative vulnerabilities with a synthetic analog of pancratistatin in combination with piperlongumine for cancer therapy

Gilbert

Pignanelli

et al. 2017

FASEB j.

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Harsh adverse effects as a result of nonspecific targeting of chemotherapeutics currently pose obstacles in cancer therapy; thus, it would be invaluable to devise novel approaches to specifically target cancer cells. The natural compound pancratistatin (PST) has been shown to preferentially induce apoptosis in a variety of cancer cell types. Recently, several analogs of PST were shown to be efficacious in inducing apoptosis in a variety of aggressive cancer cell types cancer cell mitochondrial targeting; it caused dissipation of mitochondrial membrane potential and decreased oxygen consumption, and with isolated mitochondria, it induced the release of apoptogenic factors. The natural compound piperlongumine has been shown to target the stress response to reactive oxygen species in cancer cells. We explored the combinatorial potential of two small molecules (SVTH-6 and piperlongumine) that target these vulnerabilities in cancer cells. Interestingly, when combined with the PST analog, SVTH-6, an increase in mitochondrial dysfunction was observed, leading to an enhanced cytotoxic effect against several human cancer cell types. Additionally, this combination treatment was effective in reducing cancer cell growth in physiologically more relevant 3-dimensional spheroid cell cultures. This enhanced effect was found to be dependent on reactive oxygen species generation because an antioxidant could rescue cancer cells from this combination treatment. Importantly, noncancerous cells were markedly less sensitive to this combination treatment. Thus, targeting mitochondrial and oxidative stress vulnerabilities of cancer cells could be an effective strategy for cancer therapy.-Ma, D., Gilbert, T., Pignanelli, C., Tarade, D., Noel, M., Mansour, F., Gupta, M., Ma, S., Ropat, J., Curran, C., Vshyvenko, S., Hudlicky, T., Pandey. S. Exploiting mitochondrial and oxidative vulnerabilities with a synthetic analog of pancratistatin in combination with piperlongumine for cancer therapy.

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Synthesis of C-1 homologues of pancratistatin and their preliminary biological evaluation

Cited by 33 publications

References 31 publications

Stereoselective synthesis of trans-dihydronarciclasine derivatives containing a 1,4-benzodioxane moiety

Stereoselective synthesis of trans-dihydronarciclasine derivatives containing a 1,4-benzodioxane moiety

Biological and pharmacological activities of amaryllidaceae alkaloids

Exploiting mitochondrial and oxidative vulnerabilities with a synthetic analog of pancratistatin in combination with piperlongumine for cancer therapy

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