scholarly journals Sulfamide antifolates inhibiting thymidylate synthase: synthesis, enzyme inhibition and cytotoxicity.

2002 ◽  
Vol 49 (2) ◽  
pp. 407-420 ◽  
Author(s):  
Krzysztof Pawełczak ◽  
Maciej Makowski ◽  
Michał Kempny ◽  
Jolanta M Dzik ◽  
Barbara Gołos ◽  
...  
Keyword(s):  
Thymidylate Synthase ◽  
Growth Inhibitor ◽  
Biological Evaluation ◽  
Hymenolepis Diminuta ◽  
Ehrlich Carcinoma ◽  
Thymidylate Synthases ◽  
Glutamic Acid Residue ◽  
Synthase Inhibitor ◽  
New Compounds ◽  
Synthesis And Biological Evaluation

Synthesis and biological evaluation are described of seven new analogues (3-9) of two potent thymidylate synthase inhibitors, 10-propargyl-5,8-dideazafolate (1) and its 2-methyl-2-deamino congener ICI 198583 (2). While the new compunds 3 and 4 were analogues of 1 and 2, respectively, containing a p-aminobenzenesulfonyl residue in place of the p-aminobenzoic acid residue, the remaining 5 new compounds were analogues of 4 with the L-glutamic acid residue replaced by glycine (5), L-valine (6), L-alanine (7), L-phenylglycine (8) or L-norvaline (9). The new analogues were tested as inhibitors of thymidylate synthases isolated from tumour (Ehrlich carcinoma), parasite (Hymenolepis diminuta) and normal tissue (regenerating rat liver) and found to be weaker inhibitors than the parent 10-propargyl-5,8-dideazafolic acid. Selected new analogues, tested as inhibitors of growth of mouse leukemia L 5178Y cells, were less potent than the parent 10-propargyl-5,8-dideazafolic acid. Substitution of the glutamyl residue in compound 4 with L-norvaline (9) resulted in only a 5-fold stronger thymidylate synthase inhibitor, but a 40-fold weaker cell growth inhibitor.

Synthesis and biological evaluation of S-simplexides and other analogues of simplexide

2019 ◽  
Vol 91 (7) ◽  
pp. 1257-1276
Author(s):  
Amélie Roux ◽  
Stefania Loffredo ◽  
Anne Lise Ferrara ◽  
Paul V. Murphy
Keyword(s):  
Natural Killer T Cells ◽  
Conformational Flexibility ◽  
Biological Evaluation ◽  
Immune Homeostasis ◽  
New Compounds ◽  
Stereoselective Syntheses ◽  
Synthesis And Biological Evaluation ◽  
Killer T Cells ◽  
Active Natural

Abstract Simplexides are natural glycolipids isolated from the marine sponge Plakortis simplex, and contain alkyl 4-O-(α-D-glucopyranosyl)-β-D-galactopyranoside. Simplexides can release of cytokines (IL-6) and chemokines (CXCL-8) from human monocytes and cause the expansion of natural killer T-cells (iNKTs) in vitro, with iNKTs contributing to the sustenance of immune homeostasis. Herein, the stereoselective syntheses of S-glycosidic analogues, i.e. S-simplexides, are described. The routes included Lewis acid promoted anomerisation of glycosyl thiols and thioglycolipids, as well as anomeric S-alkylation. Synthesis of O-glycosidic analogues are included. Heptadecanyl O- and S-glycosides as well as the 17-tritriacontyl 4-O-(α-D-glucopyranosyl)-β-D-galactopyranoside, a component of the natural simplexide isolate, all induced IL-6 and CXCL-8 production at both 10 and 30 μg/mL concentrations from PBMCs whereas the two S-simplexides were inactive. It is speculated that the lack of activity for the S-disaccharide analogue could be due to inhibition of cellular α-glucosidase, preventing degradation of the simplex disaccharide to a simpler galactopyranoside, whereas lack of activity for the S-galactolipid analogue could be due to increased conformational flexibility of S-glycosides. On the other hand, simpler unbranched O- and S-glycolipid analogues were active. Natural simplexide, and a synthetic simplexide, the 18-pentatriacontanyl 4-O-(α-D-glucopyranosyl)-β-D-galactopyranoside, were more potent than the new compounds tested.

scholarly journals Synthesis and Biological Evaluation of New N-Acyl-α-amino Ketones and 1,3-Oxazoles Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5019
Author(s):  
Theodora-Venera Apostol ◽  
Luminita Gabriela Marutescu ◽  
Constantin Draghici ◽  
Laura-Ileana Socea ◽  
Octavian Tudorel Olaru ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Large Family ◽  
Biological Evaluation ◽  
Reversed Phase ◽  
Bioactive Substances ◽  
Nmr Data ◽  
In Silico Studies ◽  
Ft Ir ◽  
New Compounds ◽  
Synthesis And Biological Evaluation

In order to develop novel bioactive substances with potent activities, some new valine-derived compounds incorporating a 4-(phenylsulfonyl)phenyl fragment, namely, acyclic precursors from N-acyl-α-amino acids and N-acyl-α-amino ketones classes, and heterocycles from the large family of 1,3-oxazole-based compounds, were synthesized. The structures of the new compounds were established using elemental analysis and spectral (UV-Vis, FT-IR, MS, NMR) data, and their purity was checked by reversed-phase HPLC. The newly synthesized compounds were evaluated for their antimicrobial and antibiofilm activities, for toxicity on D. magna, and by in silico studies regarding their potential mechanism of action and toxicity. The 2-aza-3-isopropyl-1-[4-(phenylsulfonyl)phenyl]-1,4-butanedione 4b bearing a p-tolyl group in 4-position exhibited the best antibacterial activity against the planktonic growth of both Gram-positive and Gram-negative strains, while the N-acyl-α-amino acid 2 and 1,3-oxazol-5(4H)-one 3 inhibited the Enterococcus faecium biofilms. Despite not all newly synthesized compounds showing significant biological activity, the general scaffold allows several future optimizations for obtaining better novel antimicrobial agents by the introduction of various substituents on the phenyl moiety at position 5 of the 1,3-oxazole nucleus.

scholarly journals Synthesis and Biological Evaluation of the Novel Growth Inhibitor Streptol Glucoside, Isolated from an Obligate Plant Symbiont

2019 ◽  
Vol 25 (7) ◽  
pp. 1722-1726 ◽  
Author(s):  
Chien-Chi Hsiao ◽  
Simon Sieber ◽  
Antri Georgiou ◽  
Aurélien Bailly ◽  
Despina Emmanouilidou ◽  
...  
Keyword(s):  
Growth Inhibitor ◽  
Biological Evaluation ◽  
The Novel ◽  
Plant Symbiont ◽  
Synthesis And Biological Evaluation

ChemInform Abstract: Antitumor Agents. Synthesis and Biological Evaluation of New Compounds Related to Podophyllotoxin, Containing the 2,3-Dihydro-1,4-benzodioxin System.

ChemInform ◽  
2010 ◽  
Vol 32 (42) ◽  
pp. no-no
Author(s):  
Alfons Sergi Capilla ◽  
Isabel Sanchez ◽  
Daniel H. Caignard ◽  
Pierre Renard ◽  
Maria Dolors Pujol
Keyword(s):  
Antitumor Agents ◽  
Biological Evaluation ◽  
New Compounds ◽  
Synthesis And Biological Evaluation

Solvent-free microwave-assisted synthesis and biological evaluation of 2,2-dimethylchroman-4-one based benzofurans

2016 ◽  
Vol 22 (6) ◽  
Author(s):  
Dongamanti Ashok ◽  
Rayagiri Suneel Kumar ◽  
Devulapally Mohan Gandhi ◽  
Madderla Sarasija ◽  
Anireddy Jayashree ◽  
...  
Keyword(s):  
Microwave Irradiation ◽  
Biological Evaluation ◽  
Solvent Free ◽  
Microwave Assisted Synthesis ◽  
Microwave Assisted ◽  
New Compounds ◽  
Synthesis And Biological Evaluation

AbstractA series of novel chroman-4-one fused benzofurans were synthesized by cyclization of the corresponding chalcones under microwave irradiation. All new compounds were characterized by IR,

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