Synthesis and biological evaluation of carbon-substituted C-4 derivatives of podophyllotoxin

Lear, Yvonne; Durst, Tony

doi:10.1139/v96-187

Cited by 9 publications

(6 citation statements)

References 12 publications

(7 reference statements)

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“…Viscous oil; R f = 0.5 (n-hexane/ethyl acetate, 1:1 vol/vol as developer), isolated yield, 97%. IR (CHCl 3 Assay for anticancer activity. The compounds 1-11 were tested for their in vitro cytotoxicity against a panel of human cancer cell lines including SK-MEL (malignant, melanoma), KB (epidermal carcinoma, oral), BT-549 (ductal carcinoma, breast), SK-OV-3 (ovary carcinoma), and HL-60 (human leukemia).…”

Section: Methodsmentioning

confidence: 99%

Synthesis and anticancer activities of fatty acid analogs of podophyllotoxin

Mustafa

Khan

et al. 2004

Lipids

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Derivatives of podophyllotoxin were prepared by coupling 10 FA with the C4-alpha-hydroxy function of podophyllotoxin. The coupling reactions between FA and podophyllotoxin were carried out by dicyclohexylcarbodiimide in the presence of a catalytic amount of dimethylaminopyridine to produce quantitative yields of desired products. FA incorporated were the following: 10-hydroxydecanoic, 12-hydroxydodecanoic, 15-hydroxypentadecanoic, 16-hydroxyhexadecanoic, 12-hydroxyoctadec-Z-9-enoic, eicosa-Z-5,8,11,14-tetraenoic, eicosa-Z-8,11, 14-trienoic, eicosa-Z-11,14-dienoic, eicosa-Z-11-enoic, and eicosanoic acids. Spectroscopic studies confirmed the formation of the desired products. New molecules were investigated for their in vitro anticancer activity against a panel of human cancer cell lines including SK-MEL, KB, BT-549, SK-OV-3 (solid tumors), and HL-60 (human leukemia) cells. Most of the analogs were cytotoxic against cancerous cells, whereas no effect was observed against normal cells, unlike the parent compound podophyllotoxin, the use of which is limited due to its severe side effects.

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Section: Methodsmentioning

confidence: 99%

Synthesis and anticancer activities of fatty acid analogs of podophyllotoxin

Mustafa

Khan

et al. 2004

Lipids

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“…Natural products have been an effective and successful method to identify novel hits and leads for curing this deadly disease (Cragg and Newman, 2013; Newman and Cragg, 2016). Podophyllotoxin (PPT, 1 ), a natural product extracted from the plants of the Podophyllum family, exhibited significant anti-tumor and anti-viral activities, attracting great interest as a hallmark molecule because of its biological activities (MacRae et al, 1989; Lear and Durst, 1996; Gordaliza et al, 2004; Nandagopal and Routh, 2017). It has been stated that PPT exerted antitumor activity via inhibiting microtubule bundle formation in mitosis metaphase, preventing the formation of the spindle and arresting cell division in metaphase (G2/M stage) (Damayanthi and Lown, 1998; Ravelli et al, 2004; Hartley et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of 4β-N-Acetylamino Substituted Podophyllotoxin Derivatives as Novel Anticancer Agents

Wei

Chen

et al. 2019

Front. Chem.

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A series of novel podophyllotoxin derivatives obtained by 4β-N-acetylamino substitution at C-4 position was designed, synthesized, and evaluated for in vitro cytotoxicity against four human cancer cell lines (EC-9706, HeLA, T-24 and H460) and a normal human epidermal cell line (HaCaT). The cytotoxicity test indicated that most of the derivatives displayed potent anticancer activities. In particular, compound 12h showed high activity with IC 50 values ranging from 1.2 to 22.8 μM, with much better cytotoxic activity than the control drug etoposide (IC 50 : 8.4 to 78.2 μM). Compound 12j exhibited a promising cytotoxicity and selectivity profile against T24 and HaCaT cell lines with IC 50 values of 2.7 and 49.1 μM, respectively. Compound 12g displayed potent cytotoxicity against HeLA and T24 cells with low activity against HaCaT cells. According to the results of fluorescence-activated cell sorting (FACS) analysis, 12g induced cell cycle arrest in the G2/M phase accompanied by apoptosis in T24 and HeLA cells. Furthermore, the docking studies showed possible interactions between human DNA topoisomerase IIα and 12g. These results suggest that 12g merits further optimization and development as a new podophyllotoxin-derived lead compound.

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“…With 8- epi -lucentamycin A ( 33 ) in hand, we evaluated its affect on an HCT-116 cell line in order to determine if the stereochemistry of the nonproteogenic 3-methyl-4-ethylideneproline nucelus was critical for biological activity. Thus, a standard 48 h cell viability assay was performed with 16 and 33 at six concentrations (0, 0.025, 0.1, 0.4, 2.0, and 10 μM) relative to podophyllotoxin as a positive control . The control performed as expected, providing an IC 50 value of 0.03 μM.…”

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confidence: 97%