Efficient oxidative dearomatisations of substituted phenols using hypervalent iodine (iii) reagents and antiprotozoal evaluation of the resulting cyclohexadienones against T. b. rhodesiense and P. falciparum Strain NF54

Quinones and quinols are secondary metabolites of higher plants that are associated with many biological activities. The oxidative dearomatization of phenols induced by hypervalent iodine(III) reagents has proven to be a very useful synthetic approach for the preparation of these compounds, which are also widely used in organic synthesis and medicinal chemistry. Starting from several substituted phenols and naphthols, a series of cyclohexadienone and naphthoquinone derivatives were synthesized using different hypervalent iodine(III) reagents and evaluated for their in vitro antiprotozoal activity. Antiprotozoal activity was assessed against Plasmodium falciparum NF54 and Trypanosoma brucei rhodesiense STIB900. Cytotoxicity of all compounds towards L6 cells was evaluated and the respective selectivity indices (SI) were calculated. We found that benzyl naphthoquinone 5c was the most active and selective molecule against T. brucei rhodesiense (IC50 = 0.08 muM, SI = 275). Furthermore, the antiprotozoal assays revealed no specific effects. In addition, some key physicochemical parameters of the synthesised compounds were calculated

Benzyl- and dibenzyl tetrahydropyridinylidene ammonium salts with antiplasmodial and antitrypanosomal activity

Several 1-benzyl and 1,3-dibenzyl derivatives of tetrahydropyridinylidene salts with differing electron withdrawing substituents at the aromatic residues have been prepared. In addition, the amine moiety in position 4 was varied. The new compounds were investigated for their antiplasmodial and antitrypanosomal activities as well as for their cytotoxicity. They were characterized using FT-IR, HRMS and NMR spectroscopy. Structure-activity relationships including reported compounds are discussed. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s)

New derivatives of the multi-stage active Malaria Box compound MMV030666 and their antiplasmodial potencies

MMV's Malaria Box compound MMV030666 shows multi-stage activity against various strains of Plasmodium falciparum and lacks resistance development. To evaluate the importance of its diarylether partial structure, diarylthioethers and diphenylamines with varying substitution patterns were prepared. A number of evident structure-activity relationships were revealed. Physicochemical and pharmacokinetic parameters were determined experimentally (passive permeability) or calculated. Compared to the lead compound a diarylthioether was more active and less cytotoxic resulting in an excellent selectivity index of 850. In addition, pharmacokinetic and physicochemical parameters were improved

Synthesis and structure-activity relationships of new 2-phenoxybenzamides with antiplasmodial activity

The 2-phenoxybenzamide 1 from theMedicines for Malaria Venture Malaria Box Project has shown promising multi-stage activity against different strains of P. falciparum. It was successfully synthesized via a retrosynthetic approach. Subsequently, twenty-one new derivatives were prepared and tested for their in vitro activity against blood stages of the NF54 strain of P. falciparum. Several insights into structure-activity relationships were revealed. The antiplasmodial activity and cytotoxicity of compounds strongly depended on the substitution pattern of the anilino partial structure as well as on the size of substituents. The diaryl ether partial structure had further impacts on the activity. Additionally, several physicochemical and pharmacokinetic parameters were calculated (log P, log D7.4 and ligand efficiency) or determined experimentally (passive permeability and CYP3A4 inhibition). The tertbutyl- 4-{4-[2-(4-fluorophenoxy)-3-(trifluoromethyl)benzamido]phenyl}piperazine-1-carboxylate possesses high antiplasmodial activity against P. falciparum NF54 (PfNF54 IC50 = 0.2690 M) and very low cytotoxicity (L-6 cells IC50 = 124.0 M) resulting in an excellent selectivity index of 460. Compared to the lead structure 1 the antiplasmodial activity was improved as well as the physicochemical and some pharmacokinetic parameters

Unexpected ring‑opening of 2,3‑dihydropyridines

The reaction of 2,3-dihydropyridines with sulfonyl halides surprisingly yielded open chain dienes with sulfonylimine structure. The products were specific out of several possible isomers and, therefore, a separation of isomers was not necessary. All new compounds were characterized using FT-IR spectroscopy, HRMS, and NMR spectroscopy. A bicyclic by-product from the reaction of a 2,3-dihydropyridine with mesyl chloride was isolated and its structure elucidated using a single X-ray crystal analysis. Some biological activities, like antimicrobial and cytotoxic properties were investigated

Die in situ-Adsorption als neuer Weg im downstream processing makromolekularer Bioprodukte

SIGLEAvailable from TIB Hannover: F04B816 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekArbeitsgemeinschaft Industrieller Forschungsvereinigungen 'Otto von Guericke' e.V. (AIF), Koeln (Germany)DEGerman