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4868 KiB

Open AccessArticle

Cytotoxic Evaluation of (2S)-5,7-Dihydroxy-6-prenylflavanone Derivatives Loaded PLGA Nanoparticles against MiaPaCa-2 Cells

by Berenice Andrade-Carrera, Beatriz Clares, Véronique Noé, Mireia Mallandrich, Ana C. Calpena, María Luisa García and María Luisa Garduño-Ramírez

Molecules 2017, 22(9), 1553; https://doi.org/10.3390/molecules22091553 - 15 Sep 2017

Cited by 18 | Viewed by 6164

Abstract

The search for new alternatives for the prevention and treatment of cancer is extremely important to minimize human mortality. Natural products are an alternative to chemical drugs, since they are a source of many potential compounds with anticancer properties. In the present study, [...] Read more.

The search for new alternatives for the prevention and treatment of cancer is extremely important to minimize human mortality. Natural products are an alternative to chemical drugs, since they are a source of many potential compounds with anticancer properties. In the present study, the (2S)-5,7-dihydroxy-6-prenylflavanone (semi-systematic name), also called (2S)-5,7-dihydroxy-6-(3-methyl-2-buten-1-yl)-2-phenyl-2,3-dihydro-4H-1-Benzopyran-4-one (CAS Name registered) (1) was isolated from Eysenhardtia platycarpa leaves. This flavanone 1 was considered as the lead compound to generate new cytotoxic derivatives 1a, 1b, 1c and 1d. These compounds 1, 1a, 1b, 1c, and 1d were then loaded in nanosized drug delivery systems such as polymeric nanoparticles (NPs). Small homogeneous spherical shaped NPs were obtained. Cytotoxic activity of free compounds 1, 1a, 1b, 1c, and 1d and encapsulated in polymeric NPs (NPs1, NPs1a, NPs1b, NPs1c and NPs1d) were evaluated against the pancreatic cancer cell line MiaPaCa-2. The obtained results demonstrated that NPs1a and NPs1b exhibited optimal cytotoxicity, and an even higher improvement of the cytotoxic efficacy was exhibited with the encapsulation of 1a. Based on these results, NPs1a were proposed as promising anticancer agent candidates. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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1868 KiB

Open AccessArticle

Chemical Synthesis of Sulfated Yeast (Saccharomyces cerevisiae) Glucans and Their In Vivo Antioxidant Activity

by Hua Zhang, Jing Zhang, Ziluan Fan, Xintao Zhou, Lin Geng, Zhenyu Wang, Joe M. Regenstein and Zhiqiang Xia

Molecules 2017, 22(8), 1266; https://doi.org/10.3390/molecules22081266 - 28 Jul 2017

Cited by 7 | Viewed by 4754

Abstract

The effects of sulfation of yeast glucans was optimized using response surface methodology. The degree of sulfation was evaluated from 0.11 to 0.75 using ion-chromatography. The structural characteristics of SYG (sulfation of yeast glucans) with a DS = 0.75 were determined using high-performance [...] Read more.

The effects of sulfation of yeast glucans was optimized using response surface methodology. The degree of sulfation was evaluated from 0.11 to 0.75 using ion-chromatography. The structural characteristics of SYG (sulfation of yeast glucans) with a DS = 0.75 were determined using high-performance liquid chromatography/gel-permeation chromatography and finally by Fourier transform infrared spectrometry. The SYG had lower viscosity and greater solubility than the native yeast glucans, suggesting that the conformation of the SYG had significantly changed. The results also showed that SYG had a significantly greater antioxidant activity in vivo compared to native yeast glucans. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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5844 KiB

Open AccessArticle

Enhanced Antibacterial Activity of Ent-Labdane Derivatives of Salvic Acid (7α-Hydroxy-8(17)-ent-Labden-15-Oic Acid): Effect of Lipophilicity and the Hydrogen Bonding Role in Bacterial Membrane Interaction

by Javier Echeverría, Alejandro Urzúa, Loreto Sanhueza and Marcela Wilkens

Molecules 2017, 22(7), 1039; https://doi.org/10.3390/molecules22071039 - 23 Jun 2017

Cited by 15 | Viewed by 5213

Abstract

In the present study, the antibacterial activity of several ent-labdane derivatives of salvic acid (7α-hydroxy-8(17)-ent-labden-15-oic acid) was evaluated in vitro against the Gram-negative bacterium Escherichia coli and the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus. For all of the [...] Read more.

In the present study, the antibacterial activity of several ent-labdane derivatives of salvic acid (7α-hydroxy-8(17)-ent-labden-15-oic acid) was evaluated in vitro against the Gram-negative bacterium Escherichia coli and the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus. For all of the compounds, the antibacterial activity was expressed as the minimum inhibitory concentration (MIC) in liquid media and minimum inhibitory amount (MIA) in solid media. Structure activity relationships (SAR) were employed to correlate the effect of the calculated lipophilicity parameters (logP_ow) on the inhibitory activity. Employing a phospholipidic bilayer (POPG) as a bacterial membrane model, ent-labdane-membrane interactions were simulated utilizing docking studies. The results indicate that (i) the presence of a carboxylic acid in the C-15 position, which acted as a hydrogen-bond donor (HBD), was essential for the antibacterial activity of the ent-labdanes; (ii) an increase in the length of the acylated chain at the C-7 position improved the antibacterial activity until an optimum length of five carbon atoms was reached; (iii) an increase in the length of the acylated chain by more than five carbon atoms resulted in a dramatic decrease in activity, which completely disappeared in acyl chains of more than nine carbon atoms; and (iv) the structural factors described above, including one HBD at C-15 and a hexanoyloxi moiety at C-7, had a good fit to a specific lipophilic range and antibacterial activity. The lipophilicity parameter has a predictive characteristic feature on the antibacterial activity of this class of compounds, to be considered in the design of new biologically active molecules. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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498 KiB

Open AccessArticle

Synthesis and Bioactivity Characterization of Scutellarein Sulfonated Derivative

by Ting Gu, Yue Zhong, Yu-Ting Lu, Ying Sun, Ze-Xi Dong, Wen-Yu Wu, Zhi-Hao Shi, Nian-Guang Li, Xin Xue, Fang Fang, He-Min Li and Yu-Ping Tang

Molecules 2017, 22(6), 1028; https://doi.org/10.3390/molecules22061028 - 21 Jun 2017

Cited by 6 | Viewed by 4641

Abstract

Scutellarin (1) has been widely used to treat acute cerebral infarction in clinic, but poor aqueous solubility decreases its bioavailability. Interestingly, scutellarin (1) could be metabolized into scutellarein (2) in vivo. In this study, a sulfonic group [...] Read more.

Scutellarin (1) has been widely used to treat acute cerebral infarction in clinic, but poor aqueous solubility decreases its bioavailability. Interestingly, scutellarin (1) could be metabolized into scutellarein (2) in vivo. In this study, a sulfonic group was introduced at position C-8 of scutellarein (2) to enhance the aqueous solubility of the obtained derivative (3). DPPH (1,1-diphenyl-2-picrylhydrazyl)-radical scavenging ability and antithrombic activity were also conducted to determine its bioactivity. The result showed that scutellarein derivate (3) could be a better agent for ischemic cerebrovascular disease treatment. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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2176 KiB

Open AccessArticle

Enhanced Production of Gypenoside LXXV Using a Novel Ginsenoside-Transforming β-Glucosidase from Ginseng-Cultivating Soil Bacteria and Its Anti-Cancer Property

by Chang-Hao Cui, Da Jung Kim, Suk-Chae Jung, Sun-Chang Kim and Wan-Taek Im

Molecules 2017, 22(5), 844; https://doi.org/10.3390/molecules22050844 - 19 May 2017

Cited by 38 | Viewed by 6607

Abstract

Minor ginsenosides, such as compound K, Rg₃(S), which can be produced by deglycosylation of ginsenosides Rb₁, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb [...] Read more.

Minor ginsenosides, such as compound K, Rg₃(S), which can be produced by deglycosylation of ginsenosides Rb₁, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb₁, is still unknown due to the rarity of its content in plants. Here, we cloned and characterized a novel ginsenoside-transforming β-glucosidase (BglG167b) derived from Microbacterium sp. Gsoil 167 which can efficiently hydrolyze gypenoside XVII into gypenoside LXXV, and applied it to the production of gypenoside LXXV at the gram-scale with high specificity. In addition, the anti-cancer activity of gypenoside LXXV was investigated against three cancer cell lines (HeLa, B16, and MDA-MB231) in vitro. Gypenoside LXXV significantly reduced cell viability, displaying an enhanced anti-cancer effect compared to gypenoside XVII and Rb₁. Taken together, this enzymatic method would be useful in the preparation of gypenoside LXXV for the functional food and pharmaceutical industries. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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2703 KiB

Open AccessArticle

AlCl₃·6H₂O-Catalyzed Friedel-Crafts Alkylation of Indoles by the para-Quinone Methide Moiety of Celastrol

by Yi Zhu, Ziwen Chen, Zhenfei Huang, Siwei Yan, Zhuoer Li, Hu Zhou, Xiaokun Zhang, Ying Su and Zhiping Zeng

Molecules 2017, 22(5), 742; https://doi.org/10.3390/molecules22050742 - 16 May 2017

Cited by 8 | Viewed by 8340

Abstract

A classical Friedel-Crafts alkylation of different indoles catalyzed by AlCl₃·6H₂O has been developed for a well-known important natural product, celastrol, resulting in a series of derivatives for further biological evaluation. The catalyst loading was reduced to 5 mol %, [...] Read more.

A classical Friedel-Crafts alkylation of different indoles catalyzed by AlCl₃·6H₂O has been developed for a well-known important natural product, celastrol, resulting in a series of derivatives for further biological evaluation. The catalyst loading was reduced to 5 mol %, the reaction proceeds at ambient temperature and reaction time is only 3 h. The product yields range from 20% to 99%. A reaction mechanism is also proposed, based on our experiment results. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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1495 KiB

Open AccessArticle

The Functional Characterization of a Site-Specific Apigenin 4′-O-methyltransferase Synthesized by the Liverwort Species Plagiochasma appendiculatum

by Hui Liu, Rui-Xue Xu, Shuai Gao and Ai-Xia Cheng

Molecules 2017, 22(5), 759; https://doi.org/10.3390/molecules22050759 - 7 May 2017

Cited by 26 | Viewed by 6376

Abstract

Apigenin, a widely distributed flavone, exhibits excellent antioxidant, anti-inflammatory, and antitumor properties. In addition, the methylation of apigenin is generally considered to result in better absorption and greatly increased bioavailability. Here, four putative Class II methyltransferase genes were identified from the transcriptome sequences [...] Read more.

Apigenin, a widely distributed flavone, exhibits excellent antioxidant, anti-inflammatory, and antitumor properties. In addition, the methylation of apigenin is generally considered to result in better absorption and greatly increased bioavailability. Here, four putative Class II methyltransferase genes were identified from the transcriptome sequences generated from the liverwort species Plagiochasma appendiculatum. Each was heterologously expressed as a His-fusion protein in Escherichia coli and their methylation activity against apigenin was tested. One of the four Class II OMT enzymes named 4′-O-methyltransferase (Pa4′OMT) was shown to react effectively with apigenin, catalyzing its conversion to acacetin. Besides the favorite substrate apigenin, the recombinant PaF4′OMT was shown to catalyze luteolin, naringenin, kaempferol, quercetin, genistein, scutellarein, and genkwanin to the corresponding 4′-methylation products. In vivo feeding experiments indicated that PaF4′OMT could convert apigenin to acacetin efficiently in E. coli and approximately 88.8 µM (25.2 mg/L) of product was synthesized when 100 µM of apigenin was supplemented. This is the first time that a Class II plant O-methyltransferase has been characterized in liverworts. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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Review

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13079 KiB

Open AccessReview

Chalcone Derivatives: Promising Starting Points for Drug Design

by Marcelo N. Gomes, Eugene N. Muratov, Maristela Pereira, Josana C. Peixoto, Lucimar P. Rosseto, Pedro V. L. Cravo, Carolina H. Andrade and Bruno J. Neves

Molecules 2017, 22(8), 1210; https://doi.org/10.3390/molecules22081210 - 25 Jul 2017

Cited by 299 | Viewed by 25433

Abstract

Medicinal chemists continue to be fascinated by chalcone derivatives because of their simple chemistry, ease of hydrogen atom manipulation, straightforward synthesis, and a variety of promising biological activities. However, chalcones have still not garnered deserved attention, especially considering their high potential as chemical [...] Read more.

Medicinal chemists continue to be fascinated by chalcone derivatives because of their simple chemistry, ease of hydrogen atom manipulation, straightforward synthesis, and a variety of promising biological activities. However, chalcones have still not garnered deserved attention, especially considering their high potential as chemical sources for designing and developing new effective drugs. In this review, we summarize current methodological developments towards the design and synthesis of new chalcone derivatives and state-of-the-art medicinal chemistry strategies (bioisosterism, molecular hybridization, and pro-drug design). We also highlight the applicability of computer-assisted drug design approaches to chalcones and address how this may contribute to optimizing research outputs and lead to more successful and cost-effective drug discovery endeavors. Lastly, we present successful examples of the use of chalcones and suggest possible solutions to existing limitations. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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4357 KiB

Open AccessReview

An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents

by Bing Xu, Gao-Rong Wu, Xin-Yu Zhang, Meng-Meng Yan, Rui Zhao, Nan-Nan Xue, Kang Fang, Hui Wang, Meng Chen, Wen-Bo Guo, Peng-Long Wang and Hai-Min Lei

Molecules 2017, 22(6), 924; https://doi.org/10.3390/molecules22060924 - 2 Jun 2017

Cited by 48 | Viewed by 7288

Abstract

Glycyrrhetinic Acid (GA), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and [...] Read more.

Glycyrrhetinic Acid (GA), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and oleanolic acid, it could trigger apoptosis in tumor cells and it can be obtained easily and cheaply, which has stimulated scientific interest in using GA as a scaffold to synthesize new antitumor agents. The structural modifications of GA reported in recent decades can be divided into four groups, which include structural modifications on ring-A, ring-C, ring-E and multiple ring modifications. The lack of a comprehensive and recent review on this topic prompted us to gather more new information. This overview is dedicated to summarizing and updating the structural modification of GA to improve its antitumor activity published between 2005 and 2016. We reviewed a total of 210 GA derivatives that we encountered and compiled the most active GA derivatives along with their activity profile in different series. Furthermore, the structure activity relationships of these derivatives are briefly discussed. The included information is expected to be of benefit to further studies of structural modifications of GA to enhance its antitumor activity. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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3633 KiB

Open AccessReview

Synthesis and Structural Modification of Marine Natural Products

by Juan Zhang, Hua Zhang, Luis Alexandre Muehlmann, Cheng-Shi Jiang and Yue-Wei Guo

Molecules 2017, 22(6), 882; https://doi.org/10.3390/molecules22060882 - 26 May 2017

Cited by 5 | Viewed by 6012

Abstract

In the last decades, marine natural products (MNPs), have attracted extensive interest from both chemists and pharmacologists due to their chemical and bioactive diversities. This special issue, collecting total synthesis and structural modification of six different type of bioactive MNPs, is expected to [...] Read more.

In the last decades, marine natural products (MNPs), have attracted extensive interest from both chemists and pharmacologists due to their chemical and bioactive diversities. This special issue, collecting total synthesis and structural modification of six different type of bioactive MNPs, is expected to inspire and attract more research effects invested into MNP research. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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