Saponins represent important natural derivatives of plant triterpenoids that are secondary plant metabolites. Saponins, also named glycoconjugates, are available both as natural and synthetic products. This review is focused on saponins of the oleanane, ursane, and lupane types of triterpenoids that include several plant triterpenoids displaying various important pharmacological effects. Additional convenient structural modifications of naturally-occurring plant products often result in enhancing the pharmacological effects of the parent natural structures. This is an important objective for all semisynthetic modifications of the reviewed plant products, and it is included in this review paper as well. The period covered by this review (2019-2022) is relatively short, mainly due to the existence of previously published review papers in recent years.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
1,10-Phenanthroline was decorated with triterpenoid-based substituents bearing additional spermine units to form amphiphilic molecules. The synthetic procedure designed for the new phenanthroline-triterpenoid amphiphiles is described in detail. Besides 1,10-phenanthroline, all target structures bear 1,4-disubstituted 1,2,3-triazole rings. The target compounds self-assembled into either helical-like or sheet-like nanostructures, depending on the structure of the target molecule, either based on betulinic acid or oleanolic acid, and on the way of binding spermine subunits to the rest of the molecules. They also proved their ability to coordinate 64Cu(II) ions. Finally, the target compounds showed cytotoxicity that was partly dependent on the formation of nanostructures.
- MeSH
- fenantroliny chemie MeSH
- kyselina olenalová * MeSH
- spermin MeSH
- triazoly MeSH
- triterpeny * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
(1) Background: To compare the effect of selected triterpenoids with their structurally resembling derivatives, designing of the molecular ribbons was targeted to develop compounds with selectivity in their pharmacological effects. (2) Methods: In the synthetic procedures, Huisgen 1,3-dipolar cycloaddition was applied as a key synthetic step for introducing a 1,2,3-triazole ring as a part of a junction unit in the molecular ribbons. (3) Results: The antimicrobial activity, antiviral activity, and cytotoxicity of the prepared compounds were studied. Most of the molecular ribbons showed antimicrobial activity, especially on Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis, with a 50-90% inhibition effect (c = 25 µg·mL-1). No target compound was effective against HSV-1, but 8a displayed activity against HIV-1 (EC50 = 50.6 ± 7.8 µM). Cytotoxicity was tested on several cancer cell lines, and 6d showed cytotoxicity in the malignant melanoma cancer cell line (G-361; IC50 = 20.0 ± 0.6 µM). Physicochemical characteristics of the prepared compounds were investigated, namely a formation of supramolecular gels and a self-assembly potential in general, with positive results achieved with several target compounds. (4) Conclusions: Several compounds of a series of triterpenoid molecular ribbons showed better pharmacological profiles than the parent compounds and displayed certain selectivity in their effects.
- Publikační typ
- časopisecké články MeSH
The subject of this review article refers to the recent achievements in the investigation of pharmacological activity and supramolecular characteristics of betulinic acid and its diverse derivatives, with special focus on their cytotoxic effect, antitumor activity, and antiviral effect, and mostly covers a period 2015-2018. Literature sources published earlier are referred to in required coherences or from historical points of view. Relationships between pharmacological activity and supramolecular characteristics are included if such investigation has been done in the original literature sources. A wide practical applicability of betulinic acid and its derivatives demonstrated in the literature sources is also included in this review article. Several literature sources also focused on in silico calculation of physicochemical and ADME parameters of the developed compounds, and on a comparison between the experimental and calculated data.
Amides of betulinic acid with cystamine were synthesized to investigate their antimicrobial and antitumor activity, and their influence on the cell cycle and cell apoptosis. The former target amide (6) displayed cytotoxicity in CEM cell line after 72 h of treatment (IC50 = 3.0 ± 0.7 μM; TI = 20), and induced apoptosis by caspase-3/7 activation in CEM cells. The latter target amide (9) displayed antimicrobial activity against Streptococcus mutans (MIC 3.125 μM; MBC 3.125 μM) and Bacillus cereus (MIC 25 μM; MBC 25 μM). The achieved results demonstrate enhancing of their biological activity over that of the parent compounds. However, two intermediate compounds (2 and 7) displayed either considerable cytotoxicity (2; 7.5 ± 0.8 μM; TI = 10, against G361) or antimicrobial activity (7; both against Actinomyces odontolycus and Clostridium perfrigens with MIC 12.5 µM and MBC 12.5 µM). The experimental data were compared with the in silico calculated physico-chemical and ADME parameters of the target compounds, including successful intermediates.
- MeSH
- Actinomyces účinky léků MeSH
- amidy chemie farmakologie MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- Bacillus cereus účinky léků MeSH
- Clostridium účinky léků MeSH
- cystamin chemie farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární konformace MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- Streptococcus mutans účinky léků MeSH
- triterpeny chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A series of picolyl amides of betulinic acid (3a-3c and 6a-6c) was prepared and subjected to the cytotoxicity screening tests. Structure-activity relationships studies resulted in finding differences in biological activity in dependence on o-, m- and p-substitution of the pyridine ring in the target amides, when cytotoxicity data of 3a-3c and 6a-6c were obtained and compared. The amides 3b and 3a displayed cytotoxicity (given in the IC50values) in G-361 (0.5 ± 0.1 μM and 2.4 ± 0.0 μM, respectively), MCF7 (1.4 ± 0.1 μM and 2.2 ± 0.2 μM, respectively), HeLa (2.4 ± 0.4 μM and 2.3 ± 0.5 μM, respectively) and CEM (6.5 ± 1.5 μM and 6.9 ± 0.4 μM, respectively) tumor cell lines, and showed weak effect in the normal human fibroblasts (BJ). Selectivity against all tested cancer cells was determined and compared to normal cells with therapeutic index (TI) between 7 and 100 for compounds 3a and 3b. The therapeutic index (TI = 100) was calculated for human malignant melanoma cell line (G-361) versus normal human fibroblasts (BJ). The cytotoxicity of other target amides (3c and 6a-6c) revealed lower effects than 3a and 3b in the tested cancer cell lines.
- MeSH
- amidy chemická syntéza chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- buněčné linie MeSH
- lidé MeSH
- molekulární struktura MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- triterpeny chemická syntéza chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A series of amphiphilic derivatives of (3β,17β)-3-hydroxyandrost-5-ene-17-carboxylic acid (1) with the polyamine spermine and three other diamines, 1,2-diaminoethane, piperazine and cadaverine, were synthesized and their antimicrobial activity and cytotoxicity were investigated. Among the target compounds, several ones showed antimicrobial activity on Gram positive and Gram negative microorganisms. The most active compounds were 20 (Streptococcus mutans CCM 7409, 3.125 µM), 16 (Streptococcus mutans CCM 7409, 12.5 µM) and 10d (Escherichia coli CCM 3954, 12.5 µM). In addition, compounds 5d, 10d, 13 and 20 displayed cytotoxicity on CEM (12.1 ± 2.1 µM, 7.6 ± 1.0 µM, 19.0 ± 0.4 µM and 5.9 ± 0.7 µM, respectively). Two additional compounds displayed medium cytotoxicity on CEM, 5a (34.6 ± 5.2 µM) and 5c (37.7 ± 5.9 µM). The compound 13 and 20 displayed high toxicity also on normal fibroblasts.
- MeSH
- androsteny chemická syntéza chemie farmakologie MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- Escherichia coli účinky léků patogenita MeSH
- kyseliny karboxylové chemická syntéza chemie farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- polyaminy chemická syntéza chemie farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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 J-type aggregates. Variable temperature DOSY-NMR spectral measurement showed non-linear dependence that also suggests self-assembly behavior of the studied systems. Chiral supramolecular structures were formed by self-assembling due to the chirality of the monomeric molecules. Application of aqueous media during self-assembly procedures is an important factor in the development of targeted drug delivery systems.
β-Sitosterol and betulinic acid were used in designing their conjugates with selected polyamines bearing either an amide bond, or an ester and an amide bond simultaneously in the target molecule. The synthesized compounds were subjected to basic cytotoxic and antimicrobial tests. The synthetic protocol is described separately for each of the three series of the target amides, because each series of compounds required a different synthetic approach. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with the tests on normal human fibroblasts. Most of the target compounds (5a-5c, 11a-11c and 16a-16c) showed medium to high cytotoxicity (0.7-7.8 μM), however, in some cases the compounds showed high cytotoxicity even toward normal human fibroblasts (11a-11c). Two compounds of this series (11c and 16c) also displayed antimicrobial activity with high and selective microbe specificity. The compound 11c was potent against Escherichia coli (minimal inhibition concentration (MIC) 6.25 μg mL(-1), i.e. 9.75 nM mL(-1)) and Staphylococcus aureus (MIC 12.5 μg mL(-1), i.e. 19.5 nM mL(-1)), and showed medium activity against Pseudomonas aeruginosa. The compound 16c was highly active against Enterococcus faecalis and S. aureus (both, MIC 3.125 μg mL(-1), i.e. 4.22 nM mL(-1)), both Gram-positive bacteria, however showed only weak activity against E. coli and no activity against P. aeruginosa, both Gram-negative bacteria, which indicates possible microbe specificity of 16c. Comparing β-sitosterol-based series (5a-5c) and betulinic acid series (11a-11c and 16a-16c) of the target compounds, the latter one gave more promising structures. The compounds 11c and 16c showed effects which may be described as multifarious activity (pleiotropic effects).
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- Escherichia coli účinky léků MeSH
- HeLa buňky MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- mikrobiální testy citlivosti MeSH
- polyaminy chemie toxicita MeSH
- Pseudomonas aeruginosa účinky léků MeSH
- sitosteroly chemie farmakologie MeSH
- Staphylococcus aureus účinky léků MeSH
- triterpeny chemie farmakologie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
The current interest of the team has been focused on investigation of novel amides with potential cytotoxicity. The presented series of compounds was synthesized from selected steryl hemiesters and heteroaromatic amines. The synthetic protocol was designed in a simple and economic way, and divided into several general methodologies applicable to the compounds synthesized. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with tests on normal human fibroblasts. Most of the lanosterol-based compounds (3-5 and 7-10) showed medium to good cytotoxicity, while only two derivatives of cholesterol (18 and 19) showed medium cytotoxicity on human T-lymphoblastic leukemia cell line. The compounds 8 and 9 displayed the reasonable cytotoxicity among this series of amides, tested on the cell lines of T-lymphoblastic leukemia [14.5±0.4 μM (8) and 18.5±3.9 μM (9)], breast adenocarcinoma [19.5±2.1 μM (8) and 23.1±4.0 μM (9)] and cervical cancer [24.8±5.3 μM (8) and 29.1±4.7 μM (9)]. Only the compound 8 was adequately less active on normal human fibroblasts (40.4±11.1 μM).
- MeSH
- amidy chemie MeSH
- aminy chemie MeSH
- cholesterol analogy a deriváty chemická syntéza farmakologie MeSH
- cytotoxiny chemická syntéza farmakologie MeSH
- fibroblasty cytologie účinky léků metabolismus MeSH
- lanosterol analogy a deriváty chemická syntéza farmakologie MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemická syntéza farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
