scholarly journals Synthesis and Biological Activities of the Optical Isomers of ( .+-. )-4-Amino-5-chloro-2-ethoxy-N-((4-(4-fluorobenzyl)-2-morpholinyl)methyl)benzamide (Mosapride).

1994 ◽  
Vol 42 (4) ◽  
pp. 877-882 ◽  
Author(s):  
Toshiya MORIE ◽  
Shiro KATO ◽  
Hiroshi HARADA ◽  
Naoyuki YOSHIDA ◽  
Jun-ichi MATSUMOTO
Keyword(s):  
Biological Activities ◽  
Optical Isomers

Chiral Forms of 4-(2',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic Acid (Flobufen) and Its Metabolite.Synthesis and Basic Biological Properties

1997 ◽  
Vol 62 (3) ◽  
pp. 498-509 ◽  
Author(s):  
Miroslav Kuchař ◽  
Marie Poppová ◽  
Antonín Jandera ◽  
Vladimíra Panajotovová ◽  
Hana Zůnová ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Biological Activities ◽  
Biological Properties ◽  
Optical Isomers ◽  
Clinical Testing ◽  
Chemical Parameters ◽  
Physico Chemical ◽  
Oxobutanoic Acid

4-(2',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (1, flobufen) is subjected to clinical testing in the treatment of rheumatoid arthritis. Owing to the occurrence of a centre of chirality, the compound exists in two enantiomers, and its major human metabolite, viz. 4-(2',4'-difluorobiphenyl-4-yl)-4-hydroxy-2-methylbutanoic acid isolated in the lactone form (2), possesses two chiral centres, making possible the existence of four stereoisomers. All of the optical isomers of the substances 1 and 2 were prepared. For flobufen (1), the racemate was separated into the stereoisomers by using the salts 3 with R-(+)- or S-(-)-1-phenylethylamine. The pairs of stereoisomers of 2, obtained by reduction of R-(+)-flobufen or the S-(-)-enantiomer, were separated by column chromatography. The physico-chemical parameters of the optical isomers were determined and some biological activities were evaluated in both in vitro and in vivo models.

scholarly journals Multidrug Resistance Modulation Activity of Silybin Derivatives and Their Anti-Inflammatory Potential

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 455 ◽  
Author(s):  
Simona Dobiasová ◽  
Kateřina Řehořová ◽  
Denisa Kučerová ◽  
David Biedermann ◽  
Kristýna Káňová ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Biological Activities ◽  
Biologically Active ◽  
Cancer Drug ◽  
Optical Isomers ◽  
Dependent Manner ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Dose Dependent

Silybin is considered to be the main biologically active component of silymarin. Its oxidized derivative 2,3-dehydrosilybin typically occurs in silymarin in small, but non-negligible amounts (up to 3%). Here, we investigated in detail complex biological activities of silybin and 2,3-dehydrosilybin optical isomers. Antioxidant activities of pure stereomers A and B of silybin and 2,3-dehydrosilybin, as well as their racemic mixtures, were investigated by using oxygen radical absorption capacity (ORAC) and cellular antioxidant activity (CAA) assay. All substances efficiently reduced nitric oxide production and cytokines (TNF-α, IL-6) release in a dose-dependent manner. Multidrug resistance (MDR) modulating potential was evaluated as inhibition of P-glycoprotein (P-gp) ATPase activity and regulation of ATP-binding cassette (ABC) protein expression. All the tested compounds showed strong dose-dependent inhibition of P-gp pump. Moreover, 2,3-dehydrosilybin A (30 µM) displayed the strongest sensitization of doxorubicin-resistant ovarian carcinoma. Despite these significant effects, silybin B was the only compound acting directly upon P-gp in vitro and also downregulating the expression of respective MDR genes. This compound altered the expression of P-glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1) and breast cancer resistance protein (BCRP, ABCG2). 2,3-Dehydrosilybin AB exhibited the most effective inhibition of acetylcholinesterase activity. We can clearly postulate that silybin derivatives could serve well as modulators of a cancer drug-resistant phenotype.

The Role of Chirality in the Activity of Photosystem II Herbicides

1987 ◽  
Vol 42 (6) ◽  
pp. 663-669 ◽  
Author(s):  
Gary Gardner ◽  
James R. Sanborn
Keyword(s):  
Photosystem Ii ◽  
Biological Activities ◽  
Critical Role ◽  
Optically Active ◽  
Chiral Discrimination ◽  
In Vitro Assays ◽  
Optical Isomers ◽  
Steric Factors

Although significant differences in activity between optical isomers have been recognized in many types of pesticides, the role of stereoselectivity has not been fully characterized for one of the most important classes of commercial herbicides, those that inhibit photosynthetic electron transport. This report describes experiments in which optically active α-methylbenzylamine or sec-butylamine was used as starting material for the synthesis of optically active triazine and urea herbicides. The biological activities of the compounds were determined in two in vitro chloroplast assays - competition for specifically bound [14C]atrazine and inhibition of photosystem II-medi- ated dye reduction - as well as in whole plant phytotoxicity. In both in vitro assays the (-)-isomer of the N-a-methylbenzyl triazine was about 15-fold more active than the (+)-isomer, and the racemate fell in between and was of about the same potency as atrazine. The same relative activities were also seen for in vivo phytotoxicity. The a-methylbenzyl urea derivatives were much less herbicidally active, but the in vitro assays were able to discriminate between the optical isomers. In both assays, the (-)-isomer of the urea was much more active than the (+)-isomer, with the racemate intermediate. Steric factors play a critical role in the degree of this chiral discrimination, since in both the corresponding triazines and ureas, the optically active molecules synthesized from the enantiomers of 2-butylamine showed only slight differences in activity. Saturation of the phenyl ring of the a-methylbenzyl triazines resulted in molecules which still showed substantial differences in activity related to chirality, further supporting the importance of steric factors, rather than electronic, in this chiral discrimination.

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