0000000000956807
AUTHOR
Zdeněk Wimmer
Polyamine conjugates of stigmasterol.
Abstract Three new polyamine conjugates with stigmasterol [(3β,22 E )-stigmasta-5,22-dien-3-ol] were synthesized and subjected to basic antimicrobial and cytotoxic tests. The conjugate derived from spermine, (3β,22 E )-stigmasta-5,22-dien-3-yl 4(12-amino-4,9-diaza-dodecylamino)-4-oxobutanoate ( 5c ), displayed considerable antimicrobial activity on Staphylococcus aureus at low concentration (50 μg mL −1 ). The cytotoxic activity was tested on cells of human T-lymfoblastic leukemia (IC 50 = 35.8 ± 10.3 μM ( 5c ) and IC 50 = 35.9 ± 5.7 μM ( 5b )) and normal human fibroblasts (IC 50 = 38.0 ± 2.8 μM ( 5c ) and IC 50 = 45.5 ± 1.9 μM ( 5b )). Conjugate 5a displayed no activity in both tests.
Crystallization, spectral, crystallographical, and thermoanalytical studies of succinobucol polymorphism.
Four different polymorphs, A, C, D, and E, of succinobucol were isolated and characterized by means of solid-state nuclear magnetic resonance spectroscopy, single crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetry, and attenuated total reflection–infrared spectroscopy. From a number of experiments, the same polymorphs (C, D, and E) and an equilibrium phase mixture B consisting of polymorphs C and D were repeatedly gained using different solvents or their mixtures. Although polymorph A was obtained directly from recrystallization only on few occasions, polymorphs C, D, and E proved to be metastable kinetic polymorphs, which slowly transform to a thermod…
Preparation and preliminary biological screening of cholic acid–juvenoid conjugates
Abstract Steroidal compounds have been utilized as carriers and for modification of physico-chemical properties of model biologically active secondary alcohols – juvenoids. Juvenoids are juvenile hormone analogues – environmentally safe insecticides, possessing significant biological activity towards different arthropods groups in focus on insect pest species. Structure modification of juvenoids plays important role to control the rate of liberation and decomposition of juvenoid in digestive system and can also play important role in the mode of action towards selected insect. This study presents an approach to the synthesis of steroidal monomers and dimers carrying one and two molecules of…
Spectral and microscopic study of self-assembly of novel cationic spermine amides of betulinic acid
Supramolecular characteristics of two spermine amides of betulinic acid (1 and 2) were studied by measuring and evaluating their UV-VIS-NIR spectra in aqueous acetonitrile and DOSY-NMR spectra in tetradeuteromethanol, accompanied by atomic force microscopy (AFM) images, scanning electron microscopy (SEM) micrographs, and transmission electron microscopy (TEM) micrographs. Fibrous supramolecular self-assembly of 1 and 2 was observed by AFM images, as well as by the SEM and TEM micrographs. Bathochromic shifts of the absorbance maximum at 870nm to 1015-970nm in the UV-VIS-NIR spectra were observed with increasing water content in the acetonitrile/water systems, indicating formation of fibrous…
Rapid Self-Healing and Thixotropic Organogelation of Amphiphilic Oleanolic Acid–Spermine Conjugates
Natural and abundant plant triterpenoids are attractive starting materials for the synthesis of conformationally rigid and chiral building blocks for functional soft materials. Here, we report the rational design of three oleanolic acid-triazole-spermine conjugates, containing either one or two spermine units in the target molecules, using the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. The resulting amphiphile-like molecules 2 and 3, bearing just one spermine unit in the respective molecules, self-assemble into highly entangled fibrous networks leading to gelation at a concentration as low as 0.5% in alcoholic solvents. Using step-strain rheological measurements, we show ra…
Rapid Self-Healing and Thixotropic Organogelation of Amphiphilic Oleanolic Acid–Spermine Conjugates
Natural and abundant plant triterpenoids are attractive starting materials for the synthesis of conformationally rigid and chiral building blocks for functional soft materials. Here, we report the rational design of three oleanolic acid–triazole–spermine conjugates, containing either one or two spermine units in the target molecules, using the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. The resulting amphiphile-like molecules 2 and 3, bearing just one spermine unit in the respective molecules, self-assemble into highly entangled fibrous networks leading to gelation at a concentration as low as 0.5% in alcoholic solvents. Using step-strain rheological measurements, we show ra…
Steroid-based gelators of A(LS)2 type: Tuning gel properties by metal coordination
By utilizing up-to-date knowledge about gelators, we designed and synthesized a novel low-molecular-weight gelator bearing a pyridine-2,6-dicarboxylic acid moiety and two cholesteryl glycinate units. In order to demonstrate the ingenuity of our design, we prepared a series of structurally related compounds and studied their gelation properties. Based on the results, we determined structural features of the gelator molecules which were important for successful gel formation. We showed that the properties of the gel systems (transparency, morphology, etc.) can be tuned by coordination with different metal ions, as well as by changing the solvent. Gelators, and their gels and xerogels were stu…
Antioxidative succinobucol–sterol conjugates: Crystal structures and pseudosymmetry in the crystals
Abstract An extensive study to attach succinobucol to sterols has provided conjugates which comprise two pharmaceutically important compounds into one entity where the components are expected to have a synergistic effect. The motivation to design these novel conjugates was the need to broaden the armamentarium of current agents used in the treatment of atherosclerotic diseases and type 2 diabetes. In desire for detailed information of these compounds in solid state, which also have an influence to their physiological activity, systematic crystallization experiments were performed and as a result, X-ray quality single crystals were obtained from four succinobucol–sterol conjugates. All of th…
Glycosidic juvenogens: derivatives bearing alpha,beta-unsaturated ester functionalities.
Abstract A series of the protected alkyl glycosides 5a / 5b – 12a / 12b was synthesized from the parent isomeric alcohols (insect juvenile hormone bioanalogs; juvenoids), 4-[4′-(2″-hydroxycyclohexyl)methylphenoxy]-3-methyl-but-2-enoic acid ethyl ester ( 1a / 1b – 4a / 4b ; racemic structures) and ( 1a – 4a ; enantiopure structures). Cadmium carbonate was used as a promoter of this Koenigs–Knorr reaction, and the products were obtained in 82–92% yields. Deprotection of the carbohydrate functionality of 5a / 5b – 12a / 12b was carefully performed using ethanolysis in the presence of zinc acetate, due to the presence of another ester functionality in the aglycone part of the molecule of protec…
Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability
Synthesis, detailed structural characterization (X-ray, NMR, MS, IR, elemental analysis), and studies of toxicity, antioxidant activity and bioavailability of unique potent anti-atherosclerotic succinobucol-steroid conjugates are reported. The conjugates consist of, on one side, the therapeutically important drug succinobucol ([4-{2,6-di-tert-butyl-4-[(1-{[3-tert-butyl-4-hydroxy-5-(propan-2-yl)phenyl]sulfanyl}ethyl)sulfanyl]phenoxy}-4-oxo-butanoic acid]) possessing an antioxidant and anti-inflammatory activity, and on the other side, plant stanol/sterols (stigmastanol, β-sitosterol and stigmasterol) possessing an ability to lower the blood cholesterol level. A cholesterol-succinobucol prodr…
Design, synthesis and stimuli responsive gelation of novel stigmasterol-amino acid conjugates.
Abstract An efficient synthesis of three novel stigmasterol-amino acid (glycine, l -leucine and l -phenylalanine) conjugates as stimuli responsive gelators is reported. The gelation properties of the prepared compounds were investigated in a variety of organic as well as aqueous solvents. The most striking finding of our investigation was that the hydrochloride salts of the prepared conjugates acted as gelators, whereas the neutral conjugates were either non-gelators or formed only a weak gel in anisole. The hydrochloride salts of stigmasteryl glycinate and l -leucinate form gels in n-alcohols (n = 4–10) and in ethane-1,2-diol, and that of stigmasteryl l -phenylalaninate forms gels in aroma…