Fistulopsines A and B antiproliferative septicine-type alkaloids from Ficus fistulosa

Yap, Veronica Alicia; Qazzaz, Mohannad E.; Raja, Vijay J.; Bradshaw, Tracey D.; Loh, Hwei‐San; Sim, Kae-Shin; Yong, Kien-Thai; Low, Yun‐Yee; Lim, Kuan‐Hon

doi:10.1016/j.phytol.2015.12.007

Cited by 18 publications

(16 citation statements)

References 22 publications

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“…Cell-cycle analysis of A549 and HK1 cells has been performed according to a previously reported method using a fluorochrome solution containing 50 mg/mL of propidium iodide (PI), 0.1 mg/mL of ribonuclease A, 0.1% v/v Triton X-100 and 0.1% w/v sodium citrate in d-H2O [23]. A549 and HK1 cells were each seeded in six-well plates at a density of 1x10 6 cells/well and treated for 24 h with 19 at its IC50 concentrations.…”

Section: Cell-cycle Analysismentioning

confidence: 99%

Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway

Break¹,

Hossan²,

Khoo³

et al. 2018

Fitoterapia

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Cardamonin is a natural chalcone that has been shown to exhibit high anticancer activity. In an attempt to discover analogues of cardamonin with enhanced anticancer activity, 19 analogues were synthesized and tested against A549 and HK1 cell lines. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin's phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19). Compound 19 was the most active analogue possessing IC values of 13.2μM and 0.7μM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. It was also able to significantly inhibit the migration of A549 and HK1 cells. Further mode of action studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell- cycle arrest in both cell lines. These events further led to the induction of apoptosis by the compound via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Moreover, 19 inhibited the expression levels of p-mTOR and p-4EBP1, which indicated that it exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway.

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Section: Cell-cycle Analysismentioning

confidence: 99%

Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway

Break¹,

Hossan²,

Khoo³

et al. 2018

Fitoterapia

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“…It could negatively regulated Met endosomal signaling in renal cancer cells and consequently inhibited the nuclear translocation of STAT3 both in vitro and in vivo (Song et al 2015 ). Another two new seco-PIA analogues, fistulopsines A ( 73 , GI 50 3.45 and 2.37 μM) and B ( 78 , GI 50 7.04 and 5.96 μM) showed in vitro growth inhibitory activity in breast carcinoma cell MCF7 and colon carcinoma cell HCT 116 cell lines, by arresting cells in G1 phase without induction of apoptosis (Yap et al 2016 ). The rare chlorinated derivative tengechlorenine ( 40 ) showed pronounced in vitro cytotoxic activity against three breast cancer cell lines tested (MDA-MB-468, MDA-MB-231, and MCF7; IC 50 values of 0.038, 0.48 and 0.91 μM) (Al-Khdhairawi et al 2017 ).…”

Section: Biological Activities Of Pias and Pqasmentioning

confidence: 99%

“…Although tylocrebrine ( 12 ) was advanced to clinical trials but failed due to its central nervous system (CNS) toxicity manifested as disorientation and ataxia, naturally occurring PIA and PQA analogues along with their total or semi synthetic derivatives still attract great attention all along as potent anti-cancer agents because of their excellent biological activities, such as the isolation of new natural analogues (Yap et al 2016 ; Al-Khdhairawi et al 2017 ; Chen et al 2019a ; Thuy et al 2019 ), new synthetic methods and new anti-cancer mechanism on active agents (Chen et al 2016 ; Wang et al 2018 ; Jo et al 2019 ; Shimada et al 2019 ), etc. Therefore, it is worthwhile to carry out further investigations on natural species and organic reactions for more novel PIA and PQA analogues with great bioeffects.…”

Section: Application Prospects Of Pias and Pqasmentioning

confidence: 99%

Possible pharmaceutical applications can be developed from naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids

Jia

Zhao

et al. 2020

Phytochem Rev

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Naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids (PIAs and PQAs) are two small groups of herbal metabolites sharing a similar pentacyclic structure with a highly oxygenated phenanthrene moiety fused with a saturated or an unsaturated N -heterocycle (indolizidine/quinolizidine moieties). Natural PIAs and PQAs only could be obtained from finite plant families (such as Asclepiadaceae, Lauraceae and Urticaceae families, etc.). Up to date, more than one hundred natural PIAs, while only nine natural PQAs had been described. PIA and PQA analogues have been applied to the development of potent anticancer agents all along because of their excellent cytotoxic activity. However, in the last two decades, other great biological properties, such as anti-inflammatory and antiviral activities were revealed successively by different pharmacological assays. Especially because of their potent antiviral activity against coronavirus (TGEV, SARS CoV and MHV) and tobacco mosaic virus, PIA and PQA analogues have attracted much pharmaceutical attention again, some of them have been used to present interesting targets for total or semi synthesis, and structure–activity relationship (SAR) study for the development of antiviral agents. In this review, natural PIA and PQA analogues obtained in the last two decades with their herbal origins, key spectroscopic characteristics for structural identification, biological activity with possible SARs and application prospects were systematically summarized. We hope this paper can stimulate further investigations on PIA and PQA analogues as an important source for potential drug discovery.

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“…Hence, more effective and potent anticancer agents are needed to save more lives from cancer death. Guided by several previous successes of isolating chemotherapeutic agents from plant sources, such as etoposide, paclitaxel, and vinblastine, considerable attention has been given to identify more effective anticancer agents or novel chemical entities from plant reservoirs [6,7,8,9,10,11,12]. Exhibiting cancer selectivity and exerting multitargeted actions for effectively killing various types of cancers, tocotrienols (T3) appear as a promising, novel anticancer candidate.…”

Section: Introductionmentioning

confidence: 99%

Tocotrienols Modulate a Life or Death Decision in Cancers

Tham

Loh

et al. 2019

IJMS

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Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.

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Fistulopsines A and B antiproliferative septicine-type alkaloids from Ficus fistulosa

Cited by 18 publications

References 22 publications

Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway

Discovery of a highly active anticancer analogue of cardamonin that acts as an inducer of caspase-dependent apoptosis and modulator of the mTOR pathway

Possible pharmaceutical applications can be developed from naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids

Tocotrienols Modulate a Life or Death Decision in Cancers

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