Total synthesis and biological evaluation of oscillatoxin D, E, and F

2021 ◽  
Author(s):  
Yusuke Araki ◽  
Yusuke Hanaki ◽  
Masaki Kita ◽  
Koutaro Hayakawa ◽  
Kazuhiro Irie ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Cell Line ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Marine Cyanobacteria ◽  
Methyl Group ◽  
Synthetic Strategy ◽  
Target Molecules ◽  
Synthesis And Biological Evaluation

Abstract Oscillatoxins (OTXs) and aplysiatoxins (ATXs) are biosynthetically related polyketides produced by marine cyanobacteria. We previously developed a synthetic route to phenolic O-methyl analogs of OTX-D and 30-methyl-OTX-D during collective synthesis of these natural products. According to our synthetic strategy, we achieved total synthesis of OTX-D, 30-methyl-OTX-D, OTX-E, and OTX-F by deprotecting the O-methyl group in an earlier intermediate, and determined their biological activities. Although OTX-D and 30-methyl-OTX-D have been reported to show anti-leukemic activity against L1210 cell line, we found that their cytotoxicity in vitro against this cell line is relatively weak (IC50: 29–52 μM). In contrast, OTX-F demonstrated cell line-selective anti-proliferative activity against DMS-114 lung cancer cells, which implies that OTXs target as yet unknown target molecules as part of this unique activity.

scholarly journals Xylochemical Synthesis and Biological Evaluation of Shancigusin C and Bletistrin G

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3224
Author(s):  
Leander Geske ◽  
Ulrich Kauhl ◽  
Mohamed E. M. Saeed ◽  
Anja Schüffler ◽  
Eckhard Thines ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Aromatic Substitution ◽  
Substitution Reactions ◽  
Total Syntheses ◽  
Wittig Olefination ◽  
Starting Point ◽  
Perkin Reaction ◽  
Synthesis And Biological Evaluation

The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regioselective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.

Biological Evaluation of Some Selected Cyclic Imides: Mitochondrial Effects and in vitro Cytotoxicity

2004 ◽  
Vol 59 (9-10) ◽  
pp. 663-672 ◽  
Author(s):  
Silvia Regina Tozado Prado ◽  
Valdir Cechinel-Filho ◽  
Fátima Campos Buzzi ◽  
Rogério Corrêa ◽  
Silvia Maria Correia Suter Cadena ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Cell Viability ◽  
Cell Line ◽  
Biological Activities ◽  
General Structure ◽  
Peritoneal Macrophages ◽  
Biological Evaluation ◽  
Rat Liver Mitochondria ◽  
Cyclic Imides

Abstract Cyclic imides such as succinimides, maleimides, glutarimides, phthalimides and their derivatives contain an imide ring and a general structure -CO-N(R)-CO- that confers hydrophobicity and neutral characteristic. A diversity of biological activities and pharmaceutical uses have been attributed to them, such as antibacterial, antifungal, antinociceptive, anticonvulsant, antitumor. In spite of these activities, much of their action mechanisms at molecular and cellular levels remain to be elucidated. We now show the effects of several related cyclic imides: maleimides (S2, S2.1, S2.2, S3), glutarimides (S4, S5, S6), 4-aminoantipyrine derivatives (L1, F1, AL1, F1.14, F1.2) and sulfonated succinimides (RO1, FA, FE, FD, MC, DMC) on isolated rat liver mitochondria, B16-F10 melanoma cell line, peritoneal macrophages and different bacterial streams. The effects on mitochondrial respiratory parameters, cell viability and antibacterial activity were also evaluated. The results indicated that S3, S5 and S6 caused an increased oxygen consumption in the presence of ADP (state III) or its absence (state IV), while all other compounds decreased those parameters at different degrees of inhibition. All the compounds decreased the respiratory control coefficient (RCC). Loss of cell viability of peritoneal macrophages and the B16- F10 cell line was observed, L1 and S2.1 being more effective. S1, S2, S3, L1 and F1 compounds showed antibacterial activity at experimental concentrations.

scholarly journals Synthesis and Biological Evaluation of S-, O- and Se-Containing Dispirooxindoles

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7645
Author(s):  
Maksim Kukushkin ◽  
Vladimir Novotortsev ◽  
Vadim Filatov ◽  
Yan Ivanenkov ◽  
Dmitry Skvortsov ◽  
...  
Keyword(s):  
Cell Line ◽  
Computational Study ◽  
Cycloaddition Reaction ◽  
Biological Evaluation ◽  
Azomethine Ylide ◽  
Prostate Cell ◽  
In Silico Study ◽  
P53 Activation ◽  
Synthesis And Biological Evaluation

A series of novel S-, O- and Se-containing dispirooxindole derivatives has been synthesized using 1,3-dipolar cycloaddition reaction of azomethine ylide generated from isatines and sarcosine at the double C=C bond of 5-indolidene-2-chalcogen-imidazolones (chalcogen was oxygen, sulfur or selenium). The cytotoxicity of these dispiro derivatives was evaluated in vitro using different tumor cell lines. Several molecules have demonstrated a considerable cytotoxicity against the panel and showed good selectivity towards colorectal carcinoma HCT116 p53+/+ over HCT116 p53−/− cells. In particular, good results have been obtained for LNCaP prostate cell line. The performed in silico study has revealed MDM2/p53 interaction as one of the possible targets for the synthesized molecules. However, in contrast to selectivity revealed during the cell-based evaluation and the results obtained in computational study, no significant p53 activation using a reporter construction in p53wt A549 cell line was observed in a relevant concentration range.

Synthesis and Biological Evaluation of Polyfluoroalkylated Antipyrines and their Isomeric O-Methylpyrazoles

2019 ◽  
Vol 15 (5) ◽  
pp. 521-536 ◽  
Author(s):  
Natalya Agafonova ◽  
Evgeny Shchegolkov ◽  
Yanina Burgart ◽  
Victor Saloutin ◽  
Alexandra Trefilova ◽  
...  
Keyword(s):  
Biological Activities ◽  
Biological Evaluation ◽  
Antipyretic Activity ◽  
Starting Point ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
Synthesis And Biological Evaluation ◽  
Cox 1

Background: Formally belonging to the non-steroidal anti-inflammatory drug class pyrazolones have long been used in medical practices. Objective: Our goal is to synthesize N-methylated 1-aryl-3-polyfluoroalkylpyrazolones as fluorinated analogs of antipyrine, their isomeric O-methylated derivatives resembling celecoxib structure and evaluate biological activities of obtained compounds. Methods: In vitro (permeability) and in vivo (anti-inflammatory and analgesic activities, acute toxicity, hyperalgesia, antipyretic activity, “open field” test) experiments. To suggest the mechanism of biological activity, molecular docking of the synthesized compounds was carried out into the tyrosine site of COX-1/2. Conclusion: The trifluoromethyl antipyrine represents a valuable starting point in design of the lead series for discovery new antipyretic analgesics with anti-inflammatory properties.

scholarly journals Synthesis and Biological Evaluation of New Substituted 3-[4-(Phenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one Derivatives asα-Glucosidase Inhibitors

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Yu-ling Wang ◽  
Ting-jian Zhang ◽  
Jing-wei Liang ◽  
Fan-hao Meng ◽  
Shao-jie Wang
Keyword(s):  
Inhibitory Activity ◽  
Methoxy Group ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Glucosidase Inhibitors ◽  
Further Development ◽  
Synthesis And Biological Evaluation

A series of new substituted 3-[4-(phenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one derivatives bearing groups methoxy,tert-butyl, and atoms of halogens at thepara-position of the A-ring were synthesized andin vitrobiological activities were evaluated as nonsugarα-glucosidase inhibitors. Most of the test compounds demonstrated significantα-glucosidase inhibitory activity relative to that of Acarbose (IC50= 29.26 μM). Thepara-substitution with a methoxy group or halogens could notably increase the potency. Compounds17,18, and23, with IC50values of 0.025 μM, 0.014 μM, and 0.018 μM, respectively, may be of significance for the further development of new nonsugarα-glucosidase inhibitors.

scholarly journals Total Synthesis Endeavors and Their Contributions to Science and Society:A Personal Account

CCS Chemistry ◽  
2019 ◽  
pp. 3-37 ◽  
Author(s):  
K. C. Nicolaou ◽  
Stephan Rigol ◽  
Ruocheng Yu
Keyword(s):  
Total Synthesis ◽  
Organic Synthesis ◽  
Materials Science ◽  
Biological Evaluation ◽  
Synthetic Methods ◽  
Design Synthesis ◽  
Current State ◽  
Target Molecules ◽  
The 19Th Century ◽  
Synthesis And Biological Evaluation

The advent of organic synthesis in the 19th century, serendipitous as it was, set in motion a revolution in science that continues to evolve into increasing levels of sophistication and to expand into new domains of science and technology for the benefits of science and society. Its evolution was always driven by the challenges posed by natural products, whose structures were becoming increasingly complex and diverse. In response to these challenges, synthetic organic chemists were prompted to sharpen their art to reach their target molecules, whose structures were often confirmed only after their synthesis in the laboratory through the art and science of total synthesis. The latter became the “locomotive” and the “flagship” of organic synthesis, for through this practice novel synthetic methods were discovered and invented, and also tested for their generality, applicability, and scope with regard to molecular complexity and diversity. The purpose of total synthesis has also evolved over the years to include aspects beyond the synthesis of the molecule and confirmation of its structure. In this article, we briefly review the evolution of total synthesis in terms of its power and reach and demonstrate its current state of the art that combines fundamentals with translational aspects through examples from our laboratories. The highlighted examples reflect the newly emerged paradigm of the discipline that includes—in addition to the total synthesis of the target molecule—structural elucidations, method discovery and development, design, synthesis, and biological evaluation of analogues for biology and medicine, and training of young students, preparing them for academic and industrial careers in the various disciplines that require knowledge and skills to practice the central science of chemical synthesis. Such disciplines include chemical biology, drug discovery and development, materials science and nanotechnology, and other endeavors whose fundamentals depend and rely on the structure of the molecule and its synthesis.

scholarly journals Bis-thiobarbiturates as Promising Xanthine Oxidase Inhibitors: Synthesis and Biological Evaluation

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1443
Author(s):  
João L. Serrano ◽  
Diana Lopes ◽  
Melani J. A. Reis ◽  
Renato E. F. Boto ◽  
Samuel Silvestre ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Biological Activities ◽  
Chemical Change ◽  
Biological Evaluation ◽  
Reference Drug ◽  
Xanthine Oxidase Inhibitors ◽  
Low Cytotoxicity ◽  
Synthesis And Biological Evaluation ◽  
Better Than

Xanthine oxidase (XO) is the enzyme responsible for the conversion of endogenous purines into uric acid. Therefore, this enzyme has been associated with pathological conditions caused by hyperuricemia, such as the disease commonly known as gout. Barbiturates and their congeners thiobarbiturates represent a class of heterocyclic drugs capable of influencing neurotransmission. However, in recent years a very large group of potential pharmaceutical and medicinal applications have been related to their structure. This great diversity of biological activities is directly linked to the enormous opportunities found for chemical change off the back of these findings. With this in mind, sixteen bis-thiobarbiturates were synthesized in moderate to excellent reactional yields, and their antioxidant, anti-proliferative, and XO inhibitory activity were evaluated. In general, all bis-thiobarbiturates present a good antioxidant performance and an excellent ability to inhibit XO at a concentration of 30 µM, eight of them are superior to those observed with the reference drug allopurinol (Allo), nevertheless they were not as effective as febuxostat. The most powerful bis-thiobarbiturate within this set showed in vitro IC50 of 1.79 μM, which was about ten-fold better than Allo inhibition, together with suitable low cytotoxicity. In silico molecular properties such as drug-likeness, pharmacokinetics, and toxicity of this promising barbiturate were also analyzed and herein discussed.

scholarly journals Design, Synthesis, and Biological Evaluation of Novel 6H-Benzo[c]chromen-6-one Derivatives as Potential Phosphodiesterase II Inhibitors

2021 ◽  
Vol 22 (11) ◽  
pp. 5680
Author(s):  
Long Tang ◽  
Jianchun Jiang ◽  
Guoqiang Song ◽  
Yajing Wang ◽  
Ziheng Zhuang ◽  
...  
Keyword(s):  
Ellagic Acid ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Cognitive Enhancer ◽  
Cell Level ◽  
Design Synthesis ◽  
Comparable Activity ◽  
Inhibitory Potential ◽  
Synthesis And Biological Evaluation

Urolithins (hydroxylated 6H-benzo[c]chromen-6-ones) are the main bioavailable metabolites of ellagic acid (EA), which was shown to be a cognitive enhancer in the treatment of neurodegenerative diseases. As part of this research, a series of alkoxylated 6H-benzo[c]chromen-6-one derivatives were designed and synthesized. Furthermore, their biological activities were evaluated as potential PDE2 inhibitors, and the alkoxylated 6H-benzo[c]chromen-6-one derivative 1f was found to have the optimal inhibitory potential (IC50: 3.67 ± 0.47 μM). It also exhibited comparable activity in comparison to that of BAY 60-7550 in vitro cell level studies.

The Synthesis and Biological Evaluation of Indolactam Alkaloids

Synthesis ◽  
2019 ◽  
Vol 51 (23) ◽  
pp. 4443-4451
Author(s):  
Manuel Mendoza ◽  
Ryan Eom ◽  
Celeste Salas ◽  
Jeremy Haynes-Smith ◽  
Kelvin L. Billingsley
Keyword(s):  
Cellular Response ◽  
Large Scale ◽  
Biological Evaluation ◽  
Scale Production ◽  
Synthetic Strategy ◽  
Kinase C ◽  
Large Scale Production ◽  
Lactam Ring ◽  
Synthesis And Biological Evaluation

In this work, we execute a general synthetic strategy to access novel indolactam alkaloids, which are agonists of protein kinase C. This protocol allowed for the most efficient reported syntheses of indolactam V (ILV) stereoisomers, while also affording the large-scale production of natural product (–)-ILV. Structure–activity studies were conducted with these compounds to elucidate the elements necessary to promote PKC-mediated cellular response. EC50 measurements in leukemia and lymphoma cell lines, as well as molecular docking analyses with the PKCδ C1B domain, provided the foundation for these studies. A distinct correlation between in vitro activity and the conformation of the macrocyclic lactam ring was discovered, which can guide design efforts for therapeutics that target the PKC regulatory domain.

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