Glycyrrhetinic amides and their cytotoxicity

3-<em>O</em>-Acetyl-glycyrrhetinic amides were prepared, and sulforhodamine B assays investigated their cytotoxicity. Their cytotoxicity strongly depended on the substitution pattern of the respective compounds. Thereby, an ethylenediamine-derived compound <strong>2</strong> performed the best, acting mainly by apoptosis. As far as heterocyclic amides are concerned, ring enlargement and the replacement of the distal nitrogen invariably led to a more or less complete loss of cytotoxic activity. Thus, the presence of a carbonyl function (C-30) seems necessary for providing significant cytotoxicity.

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Nanoemulsion Strategy for Ursolic and Oleanic Acids Isolates from Plumeria Obtusa Improves Antioxidant and Cytotoxic Activity in Melanoma Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180111151846 ◽

2018 ◽

Vol 18 (6) ◽

pp. 847-853 ◽

Cited By ~ 5

Author(s):

Helen L. Alvarado ◽

Ana C. Calpena ◽

María L. Garduño-Ramírez ◽

Raúl Ortiz ◽

Consolación Melguizo ◽

...

Keyword(s):

Cytotoxic Activity ◽

Anticancer Agents ◽

Melanoma Cell Line ◽

In Vitro Proliferation ◽

Sulforhodamine B ◽

Transmission Electron ◽

Natural Mixture ◽

Murine Melanoma Cell Line ◽

Potential Tool

Background: Triterpenoids are an important class of natural bioactive products present in many medicinal plants. Objective: The aim of present study is to investigate the antioxidant and anticarcinogenic potential of Oleanolic Acid (OA) and Ursolic Acid (UA) on B16 murine melanoma cell line isolated from Plumeria obtusa, free and loaded in a nanoemulsion (NEm) system. Methods: The nanoemulsion was characterized by dynamic light scattering, transmission electron microscopy. The viscosity was also evaluated. The antioxidant activity was determined by the reduction of 2,2-diphenyl-2- picrylhydrazyl (DPPH) free radical. In vitro proliferation studies were determined using the sulforhodamine-B method. Results: OA/UA natural mixture exhibited high percentage of inhibition of DPPH (86.06% and 85.12%, with and without irradiation). Percentages of inhibition higher than 85% in samples with and without ultraviolet irradiation were recorded when loaded in the NEm system. The natural mixture incorporated into the NEm showed cytotoxic activity from 2.9 µM, whereas the free compounds from 17.4 µM. Conclusion: We conclude that these pentacyclic triterpenes loaded in a NEm system could be considered as a new potential tool for further investigation as anticancer agents.

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Synthesis and Evaluation of Antileishmanial and Cytotoxic Activity of Benzothiopyrane Derivatives

Molecules ◽

10.3390/molecules25040800 ◽

2020 ◽

Vol 25 (4) ◽

pp. 800

Author(s):

Cristian Ortiz ◽

Fernando Echeverri ◽

Sara Robledo ◽

Daniela Lanari ◽

Massimo Curini ◽

...

Keyword(s):

Cytotoxic Activity ◽

Active Compound ◽

Structure Activity Relationship ◽

Selectivity Index ◽

Activity Relationship ◽

Carboxyl Groups ◽

Substitution Pattern ◽

Active Compounds ◽

Intracellular Amastigotes ◽

Structure Activity

In continuation of our efforts to identify promising antileishmanial agents based on the chroman scaffold, we synthesized several substituted 2H-thiochroman derivatives, including thiochromenes, thichromanones and hydrazones substituted in C-2 or C-3 with carbonyl or carboxyl groups. Thirty-two compounds were thus obtained, characterized, and evaluated against intracellular amastigotes of Leishmania (V) panamensis. Twelve compounds were active, with EC50 values lower than 40 µM, but only four compounds displayed the highest antileishmanial activity, with EC50 values below 10 µM; these all compounds possess a good Selectivity Index > 2.6. Although two active compounds were thiochromenes, a clear structure-activity relationship was not detected since each active compound has a different substitution pattern.

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Unconventional Rose Odorants: Serendipitous Discovery and Unique Olfactory Properties of 2,2-Bis(prenyl)-3-oxobutyronitrile and Its Derivatives

Synthesis ◽

10.1055/s-0037-1610199 ◽

2018 ◽

Vol 50 (22) ◽

pp. 4490-4500

Author(s):

Nicole Hauser ◽

Philip Kraft ◽

Erick Carreira

Keyword(s):

Ethyl Cyanoacetate ◽

Olfactory Receptors ◽

Underlying Structure ◽

Final Conclusion ◽

Substitution Pattern ◽

Bifunctional Compounds ◽

Odor Thresholds ◽

Direct Derivatization ◽

Derivatives Of ◽

Carbonyl Function

2,2-Bis(3-methylbut-2-enyl)-3-oxobutanenitrile [2,2-bis(prenyl)-3-oxobutyronitrile], an unusual bifunctional nitrile odorant with a fruity rosy, green odor was found to exhibit surprising differences in its detection thresholds (0.25 ng/L air for hyperosmics; 19 ng/L air for hyposmics) and perceived odor characters. To investigate this remarkable phenomenon, 13 derivatives of 2,2-bis(3-methylbut-2-enyl)-3-oxobutanenitrile were synthesized by either monoalkylation of 3-oxo-2-phenylbutanenitrile, or by dialkylation of sodium 1-cyano-2-oxopropan-1-ide or methyl or ethyl cyanoacetate, or by direct derivatization of 2,2-bis(3-methylbut-2-enyl)-3-oxobutanenitrile via its vinyl triflate and Negishi cross coupling. These systematic permutations of the substitution pattern allowed some insight to be gained into the underlying structure–odor relationships and the construction of a simple olfactophore model, albeit no final conclusion could be drawn as to whether the nitrile or carbonyl function acts as the prime osmophore of the bifunctional compounds. Depending on slight genetic variations and the corresponding differences in the receptor morphology both can engage in H-bond interactions with the olfactory receptors, which might explain the observed largely diverging sensitivities. Methyl 2-cyano-2,2-bis(3-methylbut-2-enyl)acetate with a uniform odor threshold of 0.38 ng/L air turned out to be the most interesting floral, rosy odorant of this study, followed by 3-methyl-2,2-bis(3-methylbut-2-enyl)but-3-enenitrile with only a nitrile function and varying odor thresholds (0.40 ng/L air vs. 125 ng/L air).

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Synthesis and cytotoxic activity of novel steroidal derivatives containing a [1,2,4]triazolo[1,5-a]pyrimidine ring

Journal of Chemical Research ◽

10.3184/174751917x14967701767003 ◽

2017 ◽

Vol 41 (7) ◽

pp. 413-415 ◽

Cited By ~ 2

Author(s):

Ning-Juan Fan ◽

Yuan-feng Li ◽

Shuang Liang ◽

Jiang-Jiang Tang

Keyword(s):

Cytotoxic Activity ◽

Antiproliferative Activity ◽

Pyrimidine Ring ◽

Pyrimidine Derivatives ◽

Dimethyl Oxalate ◽

Sulforhodamine B ◽

Steroidal Derivatives ◽

Mcf 7

The synthesis of steroidal derivatives containing [1,2,4]triazolo[1,5- a]pyrimidine derived from progesterone is described. The Claisen condensations of Δ1,4-pregnadien-3,20-dione and 4-chloro-Δ1,4-pregnadien-3,20-dione with dimethyl oxalate afforded 21-methoxalylpregn-1,4-diene-3,20-dione and 4-chloro-21-methoxalylpregn-1,4-diene-3,20-dione, respectively. Furthermore, the reactions of these compounds with 3-amino-1,2,4-triazole yielded the corresponding [1,2,4]triazolo[1,5- a]pyrimidine derivatives. The newly synthesised compounds were evaluated in vitro by means of sulforhodamine B assays for antiproliferative activity against HeLa and MCF-7 cells.

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Synthesis, Cyclization, and Cytotoxic Activity of 2,3-Secolupane Triterpenoids With an Ethylketone Fragment

Natural Product Communications ◽

10.1177/1934578x19878919 ◽

2019 ◽

Vol 14 (10) ◽

pp. 1934578X1987891

Author(s):

Anastasia V. Konysheva ◽

Daria V. Eroshenko ◽

Victoria V. Grishko

Keyword(s):

Double Bond ◽

Antitumor Activity ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Diphenyl Tetrazolium Bromide ◽

C 30

3-Ethyl substituted triterpenoids with a fragmented and 5-membered A ring were synthesized from the lupane ketoxime via the Beckmann reaction and intramolecular oxonitrile cyclization, respectively. Transformations of the triterpenic isopropylidene fragment with the formation of C(30) and C(20) modified derivatives were performed by either allylic C(30) oxidation or ozonolytic cleavage of the C(20)-C(29) double bond. Antitumor activity of the synthesized compounds was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,3-diphenyl-tetrazolium bromide test against 7 human cancer cell lines. Methyl 1-cyano-3-ethyl-3-oxo-2,3-seco-2-norlup-20(29)-en-30-al-28-oate (4), methyl 3-[1-bromoethyl]-1-cyano-3-oxo-2,3-seco-2-norlup-20(29)-en-30-al-28-oate (6), and methyl 1-cyano-3-ethyl-2-norlup-1(3),20(29)-dien-30-al-28-oate (9) were selected as compounds with highest cytotoxicity (IC50 1.38-15.91 μM).

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HREM interface studies in SiC-whisker-reinforced Al2O3 and Si3N4 ceramics

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100105734 ◽

1988 ◽

Vol 46 ◽

pp. 734-735

Author(s):

W. Braue ◽

R.W. Carpenter ◽

D.J. Smith

Keyword(s):

Analytical Data ◽

Base Material ◽

High Strength ◽

Ceramic Composites ◽

Good Thermal Stability ◽

All Ceramic ◽

Sic Whiskers ◽

Base Composite ◽

C 30 ◽

Si3n4 Ceramics

Whisker and fiber reinforcement has been established as an effective toughening concept for monolithic structural ceramics to overcome limited fracture toughness and brittleness. SiC whiskers in particular combine both high strength and elastic moduli with good thermal stability and are compatible with most oxide and nonoxide matrices. As the major toughening mechanisms - crack branching, deflection and bridging - in SiC whiskenreinforced Al2O3 and Si3N41 are critically dependent on interface properties, a detailed TEM investigation was conducted on whisker/matrix interfaces in these all-ceramic- composites.In this study we present HREM images obtained at 400 kV from β-SiC/α-Al2O3 and β-SiC/β-Si3N4 interfaces, as well as preliminary analytical data. The Al2O3- base composite was hotpressed at 1830 °C/60 MPa in vacuum and the Si3N4-base material at 1725 °C/30 MPa in argon atmosphere, respectively, adding a total of 6 vt.% (Y2O3 + Al2O3) to the latter to promote densification.

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Investigating the functional link between TMEM165 and SPCA1

Biochemical Journal ◽

10.1042/bcj20190488 ◽

2019 ◽

Vol 476 (21) ◽

pp. 3281-3293 ◽

Cited By ~ 2

Author(s):

Elodie Lebredonchel ◽

Marine Houdou ◽

Hans-Heinrich Hoffmann ◽

Kateryna Kondratska ◽

Marie-Ange Krzewinski ◽

...

Keyword(s):

Subcellular Localization ◽

Complete Loss ◽

Protein Family ◽

Uncharacterized Protein ◽

Functional Link ◽

P Type

TMEM165 was highlighted in 2012 as the first member of the Uncharacterized Protein Family 0016 (UPF0016) related to human glycosylation diseases. Defects in TMEM165 are associated with strong Golgi glycosylation abnormalities. Our previous work has shown that TMEM165 rapidly degrades with supraphysiological manganese supplementation. In this paper, we establish a functional link between TMEM165 and SPCA1, the Golgi Ca2+/Mn2+ P-type ATPase pump. A nearly complete loss of TMEM165 was observed in SPCA1-deficient Hap1 cells. We demonstrate that TMEM165 was constitutively degraded in lysosomes in the absence of SPCA1. Complementation studies showed that TMEM165 abundance was directly dependent on SPCA1's function and more specifically its capacity to pump Mn2+ from the cytosol into the Golgi lumen. Among SPCA1 mutants that differentially impair Mn2+ and Ca2+ transport, only the Q747A mutant that favors Mn2+ pumping rescues the abundance and Golgi subcellular localization of TMEM165. Interestingly, the overexpression of SERCA2b also rescues the expression of TMEM165. Finally, this paper highlights that TMEM165 expression is linked to the function of SPCA1.

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