Diosgenin-based thio(seleno)ureas and triazolyl glycoconjugates as hybrid drugs. Antioxidant and antiproliferative profile

Romero-Hernández, Laura L.; Merino-Montiel, Penélope; Montiel‐Smith, Sara; Meza‐Reyes, Socorro; Vega-Báez, José Luis; Abasolo, Ibane; Schwartz, Simó; López, Óscar; Fernández-Bolaños, José G.

doi:10.1016/j.ejmech.2015.05.018

Cited by 66 publications

(25 citation statements)

References 55 publications

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“…In addition, it potently suppressed cell proliferation and induced apoptosis by suppressing the p38/MAPK signaling pathway and the overexpression of DR5 [ 60 ]. Furthermore, Romero-Hernandez et al [ 61 ] demonstrated that diosgenin-derived thio(seleno)ureas and glycomimetics, bearing a 1,2,3-triazolyl tether on C-3, showed more potent anti-cancer activity against MDA-MB-231 and MCF-7 breast cancer cells, HepG2 hepatocellular carcinoma cells, and induced apoptosis, compared to its parent compound diosgenin [ 61 ]. In another study, diosgenin conjugated to methotrexate was found to be more potent in inhibiting the growth of transport-resistant breast cancer cells and dihydrofolate reductase (enzyme involved in DNA synthesis), compared to the parent diosgenin [ 62 ].…”

Section: In Vitro Anti-cancer Effects Of Diosgeninmentioning

confidence: 99%

Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

et al. 2018

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Novel and alternative options are being adopted to combat the initiation and progression of human cancers. One of the approaches is the use of molecules isolated from traditional medicinal herbs, edible dietary plants and seeds that play a pivotal role in the prevention/treatment of cancer, either alone or in combination with existing chemotherapeutic agents. Compounds that modulate these oncogenic processes are potential candidates for cancer therapy and may eventually make it to clinical applications. Diosgenin is a naturally occurring steroidal sapogenin and is one of the major bioactive compounds found in dietary fenugreek (Trigonella foenum-graecum) seeds. In addition to being a lactation aid, diosgenin has been shown to be hypocholesterolemic, gastro- and hepato-protective, anti-oxidant, anti-inflammatory, anti-diabetic, and anti-cancer. Diosgenin has a unique structural similarity to estrogen. Several preclinical studies have reported on the pro-apoptotic and anti-cancer properties of diosgenin against a variety of cancers, both in in vitro and in vivo. Diosgenin has also been reported to reverse multi-drug resistance in cancer cells and sensitize cancer cells to standard chemotherapy. Remarkably, diosgenin has also been reported to be used by pharmaceutical companies to synthesize steroidal drugs. Several novel diosgenin analogs and nano-formulations have been synthesized with improved anti-cancer efficacy and pharmacokinetic profile. In this review we discuss in detail the multifaceted anti-cancer properties of diosgenin that have found application in pharmaceutical, functional food, and cosmetic industries; and the various intracellular molecular targets modulated by diosgenin that abrogate the oncogenic process.

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Section: In Vitro Anti-cancer Effects Of Diosgeninmentioning

confidence: 99%

Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

et al. 2018

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“…Some evidence has pointed out that relatively simple selenoureas ( Figure 1A) might possess a superoxide radical scavenging activity accompanied by a low toxicity in human cells [38]. More recently, selenourea derivatives have presented anticancer and antioxidant properties, such as diosgenin derived selonourea [39], selenourea based carbonic anhydrase (hCA) inhibitor SLC-0111 [40], selenourea mimic of norepinephrine [41], and selenourea linked to tacrine [42]. Acylselenoureas have also been reported ( Figure 1B) as hCA inhibitors [43], and are conjugated with ferrocenyl moieties as antiproliferative agents [44,45].…”

Section: Introductionmentioning

confidence: 99%

Novel N,N′-Disubstituted Acylselenoureas as Potential Antioxidant and Cytotoxic Agents

et al. 2020

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Selenium compounds are pivotal in medicinal chemistry for their antitumoral and antioxidant properties. Forty seven acylselenoureas have been designed and synthesized following a fragment-based approach. Different scaffolds, including carbo- and hetero-cycles, along with mono- and bi-cyclic moieties, have been linked to the selenium containing skeleton. The dose- and time-dependent radical scavenging activity for all of the compounds were assessed using the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays. Some of them showed a greater radical scavenging capacity at low doses and shorter times than ascorbic acid. Therefore, four compounds were evaluated to test their protective effects against H2O2-induced oxidative stress. One derivative protected cells against H2O2-induced damage, increasing cell survival by up to 3.6-fold. Additionally, in vitro cytotoxic activity of all compounds was screened against several cancer cells. Eight compounds were selected to determine their half maximal inhibitory concentration (IC50) values towards breast and lung cancer cells, along with their selectivity indexes. The breast cancer cells turned out to be much more sensitive than the lung. Two compounds (5d and 10a) stood out with IC50 values between 4.2 μM and 8.0 μM towards MCF-7 and T47D cells, with selectivity indexes greater than 22.9. In addition, compound 10b exhibited dual antioxidant and cytotoxic activities. Although further evidence is needed, the acylselenourea scaffold could be a feasible frame to develop new dual agents.

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“…Three metabolites – PSA ( M2 ), TRL ( M3 ) and DSN ( M4 ) – displayed potential anticancer effects (Wang et al, ; Liu et al, ; Romero‐Hernández et al, ; Tong et al, ), thus it was of interest to evaluate the pharmacokinetic parameters during the treatment of PPI. Herein, a reliable and precise assay for the simultaneous determination of PPI and its three active metabolites in rats to support the pharmacokinetics was developed.…”

Section: Discussionmentioning

confidence: 99%

“…Steroidal saponins, which abundantly exist in Dioscoreaceae, Smilacaceae, Liliaceae and Scrophulariaceae (Guo et al, 2015;Tong et al, 2012), exert a wide variety of biological functions, including cytotoxic and anticancer activities (Zeng et al, 2014;Zhao et al, 2009). For example, prosapogenin A (PSA), trillin (TRL) and diosgenin (DSN), three typical steroidal saponins, inhibit the proliferation of a panel of human cancer cell lines, including human hepatocellular carcinoma cells, human cervical cancer cells, mcf human breast cancer cells, human leukemic cells and human promyelocytic leukemia NB(4) cells, with definite anticancer mechanisms (Liu et al, 2004;Romero-Hernández et al, 2015;Wang et al, 2013). Polyphyllin I (PPI, see Figure 1A), one of the main steroidal saponins extracted from Paris polyphylla, is regarded as a potential candidate agent for its remarkable anticancer effects (Cheung et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Metabolic profile and pharmacokinetics of polyphyllin I, an anticancer candidate, in rats by UPLC‐QTOF‐MS/MS and LC‐TQ‐MS/MS

Yu-Cai¹,

Zhu

Shakya

et al. 2016

Biomedical Chromatography

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Polyphyllin I (PPI), a natural steroidal saponin originating from rihzome of Paris polyphylla, is a potential anticancer candidate. Previous pharmacokinetics study showed that the oral bioavailability of PPI was very low, which suggested that certain amount of PPI might be metabolized in vivo. However, to date, information regarding the final metabolic fates of PPI is very limited. In this study, metabolites of PPI and their pharmacokinetics in rats were investigated using UPLC-QTOF-MS/MS and LC-TQ-MS/MS. A total of seven putative metabolites, including six phase I and one phase II metabolites, were detected and identified with three exact structures by comparison with authentic standards for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. The pharmacokinetics of prosapogenin A, trillin and diosgenin, three deglycosylation metabolites of PPI with definite anticancer effects, were further studied, which suggested that the metabolites underwent a prolonged absorption and slower elimination after intragastric administration of PPI at the dose of 500 mg/kg. This study provides valuable and new information on the metabolic fate of PPI, which will be helpful in further understanding its mechanism of action.

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Diosgenin-based thio(seleno)ureas and triazolyl glycoconjugates as hybrid drugs. Antioxidant and antiproliferative profile

Cited by 66 publications

References 55 publications

Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

Novel N,N′-Disubstituted Acylselenoureas as Potential Antioxidant and Cytotoxic Agents

Metabolic profile and pharmacokinetics of polyphyllin I, an anticancer candidate, in rats by UPLC‐QTOF‐MS/MS and LC‐TQ‐MS/MS

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