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Journal ArticleDOI

Patent survey of resveratrol, taxol, podophyllotoxin, withanolides and their derivatives used in anticancer therapy.

31 Jul 2017-Recent Patents on Biotechnology (Bentham Science Publishers Ltd.)-Vol. 11, Iss: 2, pp 85-100

TL;DR: A general outline to search the freely accessible WIPO, EPO, USPTO and Cambia databases with several keywords and patent codes with results indicative of being both database-specific as well as queryspecific are provided.
Abstract: BACKGROUND Resveratrol, taxol, podophyllotoxin, withanolides and their derivatives find applications in anti-cancer therapy. They are plant-derived compounds whose chemical structures and synthesis limit their natural availability and restrict a large-scale industrial production. Hence, their production by various biotechnological approaches may hold promise for a continuous and reliable mode of supply. OBJECTIVE We review process and product patents in this regard. METHODS Accordingly, we provide a general outline to search the freely accessible WIPO, EPO, USPTO and Cambia databases with several keywords and patent codes. We have tabulated both granted and filed patents from the said databases. RESULTS AND CONCLUSION We retrieved ~40 patents from these databases. Novel biotechnological processes for production of these anticancer compounds include Agrobacterium rhizogenes-mediated hairy root culture, suspension culture, cell culture with elicitors, use of recombinant microorganisms, and bioreactors among others. The results are indicative of being both database-specific as well as queryspecific. A ten-year search window yielded 33 patents. The utility of the search strategy is discussed in the light of biotechnological developments in the field. Those who examine patent literature using similar search strategies may complement their knowledge obtained from perusal of mainstream journal resources.
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Journal ArticleDOI
Chih Fung Wu1, Man Gang Lee, Mohamed El-Shazly2, Kuei Hung Lai  +7 moreInstitutions (5)
TL;DR: The cytotoxic effect of isoaaptamine is associated with the induction of apoptosis and autophagy through oxidative stress and represents an interesting drug lead in the war against breast cancer.
Abstract: Aaptos is a genus of marine sponge which belongs to Suberitidae and is distributed in tropical and subtropical oceans. Bioactivity-guided fractionation of Aaptos sp. methanolic extract resulted in the isolation of aaptamine, demethyloxyaaptamine, and isoaaptamine. The cytotoxic activity of the isolated compounds was evaluated revealing that isoaaptamine exhibited potent cytotoxic activity against breast cancer T-47D cells. In a concentration-dependent manner, isoaaptamine inhibited the growth of T-47D cells as indicated by short-(MTT) and long-term (colony formation) anti-proliferative assays. The cytotoxic effect of isoaaptamine was mediated through apoptosis as indicated by DNA ladder formation, caspase-7 activation, XIAP inhibition and PARP cleavage. Transmission electron microscopy and flow cytometric analysis using acridine orange dye indicated that isoaaptamine treatment could induce T-47D cells autophagy. Immunoblot assays demonstrated that isoaaptamine treatment significantly activated autophagy marker proteins such as type II LC-3. In addition, isoaaptamine treatment enhanced the activation of DNA damage (γH2AX) and ER stress-related proteins (IRE1 α and BiP). Moreover, the use of isoaaptamine resulted in a significant increase in the generation of reactive oxygen species (ROS) as well as in the disruption of mitochondrial membrane potential (MMP). The pretreatment of T-47D cells with an ROS scavenger, N-acetyl-l-cysteine (NAC), attenuated the apoptosis and MMP disruption induced by isoaaptamine up to 90%, and these effects were mediated by the disruption of nuclear factor erythroid 2-related factor 2 (Nrf 2)/p62 pathway. Taken together, these findings suggested that the cytotoxic effect of isoaaptamine is associated with the induction of apoptosis and autophagy through oxidative stress. Our data indicated that isoaaptamine represents an interesting drug lead in the war against breast cancer.

17 citations


Journal ArticleDOI
Ting Liang1, Xiangyang Sun1, Wenhong Li1, Guihua Hou1  +1 moreInstitutions (1)
Abstract: Lung cancer is the most common malignancy and leads to around one-quarter of all cancer deaths. Great advances have been achieved in the treatment of lung cancer with novel anticancer agents and improved technology. However, morbidity and mortality rates remain extremely high, calling for an urgent need to develop novel anti-lung cancer agents. 1,2,3-Triazole could be readily interact with diverse enzymes and receptors in organisms through weak interaction. 1,2,3-Triazole not only can be acted as a linker to tether different pharmacophores, but also can serve as a pharmacophore. This review aims to summarize the recent advances in 1,2,3-triazole-containing compounds with anti-lung cancer potential, and their structure-activity relationship (SAR) together with mechanisms of action is also discussed to pave the way for the further rational development of novel anti-lung cancer candidates.

5 citations


Journal ArticleDOI
Jinbao Wei1, Jinbao Wei2, Jinghong Chen2, Peijun Ju2  +6 moreInstitutions (2)
TL;DR: The cytotoxicity test indicated that 12g merits further optimization and development as a new podophyllotoxin-derived lead compound, and the docking studies showed possible interactions between human DNA topoisomerase IIα and 12g.
Abstract: 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 IC50 values ranging from 1.2 to 22.8 μM, with much better cytotoxic activity than the control drug etoposide (IC50: 8.4 to 78.2 μM). Compound 12j exhibited a promising cytotoxicity and selectivity profile against T24 and HaCaT cell lines with IC50 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.

4 citations


Book ChapterDOI
01 Jan 2021
TL;DR: Goji berries seem to be a highly promising natural medicine in anticancer prevention and treatment because of their high content of active compounds.
Abstract: Lycium barbarum (goji berry) belongs to the group of plants that exhibit human health benefits such as antioxidant and anticancer effects These effects are the results of high levels of polysaccharides, polyphenols, flavonoids, carotenoids, and their derivatives in these plants These compounds are able to neutralize free radicals, impacting cellular homeostasis maintenance, and intracellular signaling pathways Extracted fractions from goji berries, depending on their types and abundance of individual compounds, show antiproliferative properties against different types of cancer, including breast carcinoma, whereas their cytotoxic effect on human normal cells has not been demonstrated A pectin-free fraction of goji berry extract induces growth inhibition of MCF7 and MDA-MB-231 breast cancer cell lines, while ethanol extract inhibits proliferation of T47D cell line in a time- and dose-dependent manner Additionally, polysaccharides from Lycium barbarum (LBPs) modulates estrogen metabolism, activates the extracellular signal-reduced kinase 1/2 (ERK 1/2) pathway, and increases the expression level of p53 Taken together, goji berries seem to be a highly promising natural medicine in anticancer prevention and treatment because of their high content of active compounds

1 citations


Journal ArticleDOI
TL;DR: The use of SLN for the delivery of Docetaxel to tumor site have several benefits like site specific delivery, less toxic effect, more cell cytotoxicity and more bioavaibility which leads to decrease in the dosing frequency.
Abstract: Solid lipid nanoparticles are the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine and research. Due to its solid state it has greater stability than other nanocarrier systems. There are several other advantages like sustained release, improves bioavaibility and delivery of poorly water soluble drugs, helps in control of several pharmacokinetic parameters of drugs due to which use of SLN is increasing day by day. Various techniques can be used for the formulation of SLN i.e. solvent evaporation, microemulsification technique, high pressure homogenization and supercritical fluid method. It has several applications likes it is use in gene transfer therapy, also use in different drug delivery systmer like oral and pulmonary drug delivery system. Due to several advantages SLNs are widely used in chemotherapy for the treatment of the cancer. The use of SLN for the delivery of Docetaxel to tumor site have several benefits likes site specific delivery, less toxic effect, more cell cytotoxicity and more bioavaibility which leads to decrease in the dosing frequency. Docetaxel is an anticancer agent extracted from plant Taxus Baccata which is widely used in chemotherapy to treat cancer. This article contains the detail information of about the advantages, disadvantages, different method of preparation and several SLN loaded with Docetaxel. Keywords: Solid lipid nanoparticles, drug delivery, clinical medicine, poorly water soluble drugs

1 citations


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