scholarly journals Structural Modification of the Macrolide Brefeldin A to Analogues with Enhanced Cytotoxicity against KB Cells

2021 ◽  
Vol 18 (21) ◽  
pp. 44
Author(s):  
Maneekarn Namsa-Aid ◽  
Suthep Wiyakrutta ◽  
Surasak Prachya ◽  
Anucha Namsa-Aid ◽  
Apichart Suksamrarn
Keyword(s):  
Structural Modification ◽  
Parent Compound ◽  
Brefeldin A ◽  
Hydroxyl Group ◽  
Public Health Issue ◽  
Kb Cells ◽  
Lower Toxicity ◽  
Ic50 Value ◽  
Free Hydroxyl ◽  
High Cytotoxicity

The macrolide brefeldin A (BFA, 1) exhibited high cytotoxicity against KB cells. However, it was also toxic against non-cancerous cells. In order to lower toxicity against normal cells while maintaining the cytotoxic potency to the cancer cells, structural modification of this compound was undertaken. Starting from compound 1, the analogues 2-13 were synthesized and evaluated for cytotoxicity against KB cells. The analogue 2 exhibited the most potent cytotoxicity against KB cells, with an IC50 value of 0.034 nM, 67-fold more active than its parent compound 1. It was 41764 and 8235 fold more active than the standard drugs ellipticine and doxorubicin, respectively. The higher cytotoxicity against KB cells and lower toxicity against Vero cells of analogue 2 than those of the parent compound 1 contributed to its exceptionally high selectivity index of 9117. The results suggested that this analogue might be utilized to develop a new candidate for an anticancer drug. HIGHLIGHTS Oral cancer is a major worldwide public health issue and may affect any oral cavity region, including the lips, tongue, mouth and throat The ester analogues (2-13) were the first report of the cytotoxic against human epidermoid carcinoma (KB) cells 7-O-acetyl BFA (2) exhibited the most potent cytotoxicity against KB cells, with an IC50 value of 034 nM, 67-fold more active than its parent compound 1 The essentially structural features for the macrolide of BFA-type to exhibit high cytotoxicity against KB cells are the presence of a free hydroxyl group at the 4-position, a free hydroxyl group or the corresponding ester at the 7-position, and unsaturated functions at the 2- and 10-positions GRAPHICAL ABSTRACT

Combinatorial Synthesis of Novel 9R-Acyloxyquinine Derivatives as Insecticidal Agents

2020 ◽  
Vol 23 (2) ◽  
pp. 111-118
Author(s):  
Zhiping Che ◽  
Jinming Yang ◽  
Di Sun ◽  
Yuee Tian ◽  
Shengming Liu ◽  
...  
Keyword(s):  
Natural Products ◽  
Double Bond ◽  
Insecticidal Activity ◽  
Structural Modification ◽  
Combinatorial Synthesis ◽  
Hydroxyl Group ◽  
Botanical Insecticide ◽  
Mythimna Separata ◽  
Lead Compounds

Background: It is one of the effective ways for pesticide innovation to develop new insecticides from natural products as lead compounds. Quinine, the main alkaloid in the bark of cinchona tree as well as in plants in the same genus, is recognized as a safe and potent botanical insecticide to many insects. The structural modification of quinine into 9R-acyloxyquinine derivatives is a potential approach for the development of novel insecticides, which showed more toxicity than quinine. However, there are no reports on the insecticidal activity of 9Racyloxyquinine derivatives to control Mythimna separata. Methods: Endeavor to discover biorational natural products-based insecticides, 20 novel 9Racyloxyquinine derivatives were prepared and assessed for their insecticidal activity against M. separata in vivo by the leaf-dipping method at 1 mg/mL. Results: Among all the compounds, especially derivatives 5i, 5k and 5t exhibited the best insecticidal activity with final mortality rates of 50.0%, 57.1%, and 53.6%, respectively. Conclusion: Overall, a free 9-hydroxyl group is not a prerequisite for insecticidal activity and C9- substitution is well tolerated; modification of out-ring double-bond is acceptable, and hydrogenation of double-bond enhances insecticidal activity; Quinine ring is essential and open of it is not acceptable. These preliminary results will pave the way for further modification of quinine in the development of potential new insecticides.

scholarly journals Studies on the formation of complex oxidation and condensation products of phenols. Part III. -Rearrangements of oxidation-reduction type in the diquinone group

1933 ◽  
Vol 143 (848) ◽  
pp. 223-228 ◽  
Keyword(s):  
Hydroxyl Group ◽  
Hydrogen Atoms ◽  
Blue Colour ◽  
Highly Active ◽  
Oxidation Reduction ◽  
Intramolecular Reactions ◽  
Trimethyl Ether ◽  
Free Hydroxyl ◽  
Ethereal Oxygen ◽  
Complex Oxidation

The diquinones have been but little investigated, and as they contain two condensed highly active quinonid systems it is to be anticipated that they should be capable of interesting intramolecular reactions. When heated to 210-215º, 4 : 4'-dimethoxydiquinone is rapidly converted into a red crystalline isomeride (yield, 90%), soluble in alkali with an intense blue colour, and yielding a mono-acetate indicating the occurrence of a free hydroxyl group. Two hydrogen atoms are taken up on reduction, and the phenolic product yields a triacetate and a trimethyl ether. It follows that of the four carbonyl oxygens of 4 : 4'-dimethoxydiquinone, one has been converted into a hydroxyl group, and another which does not exhibit any functional activity, is probably present as ethereal oxygen. These results led to formula (III) as representing the product of rearrangement.

scholarly journals Synthesis and Characterizations of Dipeptide Derivative of Gentamicin

2019 ◽  
Vol 28 (2) ◽  
pp. 73-82
Author(s):  
Oun D. Khudair ◽  
Diar A. Fatih
Keyword(s):  
Acid Chloride ◽  
Solution Method ◽  
Hydroxyl Group ◽  
Hydroxyl Groups ◽  
Free Hydroxyl ◽  
Ester Linkage ◽  
Amine Groups ◽  
Conventional Solution ◽  
Dipeptide Derivative

Abstract       The target derivative are gentamicin linked with L-Val- L-Ala by an ester linkage. These were synthesized by esterification method, which included the reaction of -OH hydroxyl group on (carbon No.5) of gentamicin with the acid chloride of the corresponding dipeptide, The preparation of new derivative of gentamicin involved protected the primary & secondary amine groups of Gentamicin, by Ethylchloroformate (ECF) to give N-carbomethoxy Gentamicin which was used for further chemical synthesis involving the free hydroxyl groups. Then prepared dipeptide (L-Val- L-Ala) by conventional solution method in present DCC & HoBt then reacted with thionyl chloride to prepared acid chloride of dipeptides, then after, linked by ester linkage to N-protection gentamicin in present pyridine as base, finally deportation the amino group of synthesized compound by using TFAA in present anisole. The characterization of the titled compounds were performed utilizing FTIR spectroscopy, CHNS elemental analysis, and by measurements of their physical properties.  

scholarly journals Terpenoids from the Deep-Sea-Derived Fungus Penicillium thomii YPGA3 and Their Bioactivities

Marine Drugs ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 164 ◽  
Author(s):  
Zhongbin Cheng ◽  
Wan Liu ◽  
Runzhu Fan ◽  
Shouye Han ◽  
Yuanli Li ◽  
...  
Keyword(s):  
Deep Sea ◽  
Chemical Study ◽  
Positive Control ◽  
Hydroxyl Group ◽  
Etoac Extract ◽  
The Third ◽  
Ic50 Value ◽  
Ic50 Values ◽  
New Compounds ◽  
First Time

A chemical study of the ethyl acetate (EtOAc) extract from the deep-sea-derived fungus Penicillium thomii YPGA3 led to the isolation of a new austalide meroterpenoid (1) and seven known analogues (2−8), two new labdane-type diterpenoids (9 and 10) and a known derivative (11). The structures of new compounds 1, 9, and 10 were determined by comprehensive analyses via nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data. The absolute configurations of 1, 9, and 10 were determined by comparisons of experimental electronic circular dichroism (ECD) with the calculated ECD spectra. Compound 1 represented the third example of austalides bearing a hydroxyl group at C-5 instead of the conserved methoxy in other known analogues. To our knowledge, diterpenoids belonging to the labdane-type were discovered from species of Penicillium for the first time. Compound 1 showed cytotoxicity toward MDA-MB-468 cells with an IC50 value of 38.9 μM. Compounds 2 and 11 exhibited inhibition against α-glucosidase with IC50 values of 910 and 525 μM, respectively, being more active than the positive control acarbose (1.33 mM).

scholarly journals Cytotoxic Sesquiterpenoids from the Stem Bark of Aglaia harmsiana (Meliaceae)

2020 ◽  
Vol 20 (6) ◽  
pp. 1448
Author(s):  
Hersa Milawati ◽  
Winda Sukmawati ◽  
Desi Harneti ◽  
Rani Maharani ◽  
Nurlelasari Nurlelasari ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Stem Bark ◽  
Hydroxyl Group ◽  
Breast Cancer Cell Lines ◽  
Spectroscopy Analysis ◽  
Chemical Structures ◽  
Ic50 Value ◽  
First Time ◽  
Mass Spectroscopy Analysis ◽  
Mcf 7

Three aromadendrane-type sesquiterpenoids, spathulenol (1), 4β,10α-dihydroxyaromadendrane (2), and 4α,10α-dihydroxyaromadendrane (3) were isolated from the stem bark of Aglaia harmsiana (Meliaceae). Compound 3 was isolated for the first time from Aglaia genus. The chemical structures of isolated compounds were elucidated by various spectroscopic methods, including one and two-dimensional NMR, as well as mass spectroscopy analysis. These sesquiterpenoids 1-3 were evaluated for their cytotoxic activity against MCF-7 breast cancer cell lines. The IC50 value of compound 1-3 were 31.65 ± 0.1, 8.41 ± 0.04 and 2.80 ± 0.02 µM, respectively. Among the aromadendrane-type sesquiterpenoids, compounds 2 and 3, which do not have a double bond, showed higher activity than compound 1. Whereas, compound 3 showed the strongest activity indicate that α configuration of hydroxyl group increases the cytotoxic activity.

Gas-chromatographic method for acetaminophen (N-acetyl-p-aminophenol) based on sequential alkylation.

1976 ◽  
Vol 22 (6) ◽  
pp. 879-883 ◽  
Author(s):  
W A Dechtiaruk ◽  
G F Johnson ◽  
H M Solomon
Keyword(s):  
Serum Concentration ◽  
Chromatographic Method ◽  
Parent Compound ◽  
Internal Standard ◽  
Amide Group ◽  
Phenolic Hydroxyl ◽  
Hydroxyl Group ◽  
Methyl Derivative ◽  
Chromatographic Procedure ◽  
Gas Chromatographic Method

Abstract A gas-chromatographic procedure for acetaminophen is described in which the drug is chromatographed as the O-heptyl-N-methyl derivative. This derivative is prepared by a sequential alkylation procedure in which the phenolic hydroxyl group of the parent compound is alkylated off-column with heptyl iodide and the amide group is derivatized on-column by reaction with trimethylanilinium hydroxide. The internal standard, N-propionyl-p-aminophenol, is subjected to the same derivatization procedure. This gas-chromatographic procedure correlates well with conventional colorimetric and spectrophotometric procedures for acetaminophen and is more sensitive. Within-run precision (CV) was 2.0% at a serum concentration of 10.0 mg/liter (n = 10) and between-run precision was 4.0% over a period of eight months. This method is particularly applicable to studies of the pharmacokinetics of acetaminophen.

scholarly journals Improvement of Naturally Derived Food Colorant Performance with Efficient Pyranoanthocyanin Formation from Sambucus nigra Anthocyanins Using Caffeic Acid and Heat

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5998
Author(s):  
Nicole Straathof ◽  
M. Monica Giusti
Keyword(s):  
Caffeic Acid ◽  
Hydroxyl Group ◽  
Effect Of Temperature ◽  
Red Wines ◽  
Plant Pigments ◽  
Sambucus Nigra ◽  
Molar Ratios ◽  
Free Hydroxyl ◽  
Compositional Changes ◽  
C 50

Consumers and regulations encourage the use of naturally derived food colorants. Anthocyanins (ACN), plant pigments, are unstable in foods. In aged red wines, ACN with a free hydroxyl group at C-5 condenses to form pyranoanthocyanins (PACN), which are more stable but form inefficiently. This study attempted to produce PACN efficiently using high cofactor concentration and heat. Elderberry anthocyanins were semi-purified and caffeic acid (CA) was dissolved in 15% ethanol and diluted with a buffer to achieve ACN:CA molar ratios of 1:50, 1:100, 1:150, and 1:200, then incubated at 65 °C for 5 days. The effect of temperature was tested using ACN samples incubated with or without CA at 25 °C, 50 °C, and 75 °C for 7 days. Compositional changes were monitored using uHPLC-PDA-MS/MS. Higher CA levels seemed to protect pigment integrity, with ACN:CA 1:150 ratio showing the highest tinctorial strength after 48 h. PACN content growth was fastest between 24 and 48 h for all ACN:CA ratios and after 120 h, all ACN had degraded or converted to PACN. PACN formed faster at higher temperatures, reaching ~90% PACN in 24 h and ~100% PACN in 48 h at 75 °C. These results suggest that PACN can form efficiently from elderberry ACN and CA if heated to produce more stable pigments.

Structural modification of zolpidem led to potent antimicrobial activity in imidazo[1,2-a]pyridine/pyrimidine-1,2,3-triazoles

2019 ◽  
Vol 43 (41) ◽  
pp. 16281-16299 ◽  
Author(s):  
Rajkumar Reddyrajula ◽  
Udaya Kumar Dalimba
Keyword(s):  
Antimicrobial Activity ◽  
Structural Modification ◽  
Parent Compound ◽  
Antitubercular Activity ◽  
Structural Modifications

New imidazo[1,2-a]pyridine/pyrimidine-1,2,3-triazoles (IPTs) designed by specific structural modifications of zolpidem exhibited superior antitubercular activity than the parent compound.

Growth Inhibitory Properties of Synthetic Chalcones

2020 ◽  
Vol 16 (6) ◽  
pp. 892-899
Author(s):  
Gajanan D. Kottapalle ◽  
Nagesh J. Deshmukh ◽  
Avinash T. Shinde
Keyword(s):  
Antibacterial Activity ◽  
Condensation Reaction ◽  
Aromatic Aldehydes ◽  
Hydroxyl Group ◽  
Diffusion Method ◽  
Bacillus Species ◽  
Interesting Insight ◽  
Growth Inhibitory ◽  
Free Hydroxyl ◽  
Target Molecules

Background: In the present study, chalcones were synthesized from 2-hydroxy-1- acetonaphthone and substituted aromatic aldehydes were synthesized by Claisen Schmidt condensation reaction using potassium hydroxide as a base. The synthesized chalcones were purified by recrystallization from ethanol and evaluated for antibacterial activity by well diffusion method. The antibacterial activity was evaluated against Bacillus licheniformis, Bacillus species, Escherichia coli and Staphylococcus aureus using Ciprofloxacin as a standard. Methods: The target molecules were prepared by reacting 2-hydroxy-1-acetonaphthone and various substituted aromatic aldehyde in the presence of suitable condensing agents. The structure of synthesized compounds was confirmed on the basis of elemental analysis, IR, 1H NMR and 13C NMR spectral data. These synthesized compounds were also screened for antibacterial activity. Results: In the present study, free hydroxyl group in position 2 or 4 of aldehyde ring of synthesized chalcones appears to be a very important requirement in increasing the activity (2-5 and 8-13). When the hydroxyl group in position 4 is alkylated (14, 15), the chalcones become less active. When more complex substituent is present on the aldehyde ring (6, 7) there is a decrease in the activity. Conclusion: Newly synthesized chalcones (1-15) show good and moderate antibacterial activity. We believe that the new hydroxy substituted (in aldehyde ring) chalcones (2-5 and 8-13) reported in this work may provide an interesting insight for further optimization.

Investigations into the decomposition of aminoacyl-substituted monosaccharide scaffolds from a drug discovery library

2015 ◽  
Vol 13 (13) ◽  
pp. 4070-4079 ◽  
Author(s):  
Q. Q. He ◽  
N. Wimmer ◽  
G. Verquin ◽  
W. Meutermans ◽  
V. Ferro
Keyword(s):  
Drug Discovery ◽  
Acyl Transfer ◽  
Hydroxyl Group ◽  
Side Chain ◽  
Free Hydroxyl ◽  
Acidic Conditions

Decomposition of aminoacyl-substituted d-galactoside scaffolds under acidic conditions is dependent on the length of the side chain and is accelerated by the presence of a free hydroxyl group at C-6. In the latter case, evidence is provided that the reaction occurs via an N- to O-acyl transfer.

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