The development of stimuli-responsive drug delivery systems enables targeted delivery and environment-controlled drug release, thereby minimizing off-target effects and systemic toxicity. We prepared and studied tailor-made dual-responsive systems (thermo- and pH-) based on synthetic diblock copolymers consisting of a fully hydrophilic block of poly[N-(1,3-dihydroxypropyl)methacrylamide] (poly(DHPMA)) and a thermoresponsive block of poly[N-(2,2-dimethyl-1,3-dioxan-5-yl)methacrylamide] (poly(DHPMA-acetal)) as drug delivery and smart stimuli-responsive materials. The copolymers were designed for eventual medical application to be fully soluble in aqueous solutions at 25 °C. However, they form well-defined nanoparticles with hydrodynamic diameters of 50-800 nm when heated above the transition temperature of 27-31 °C. This temperature range is carefully tailored to align with the human body's physiological conditions. The formation of the nanoparticles and their subsequent decomposition was studied using dynamic light scattering (DLS), transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and nuclear magnetic resonance (NMR). 1H NMR studies confirmed that after approximately 20 h of incubation at pH 5, which closely mimics tumor microenvironment, approximately 40% of the acetal groups were hydrolyzed, and the thermoresponsive behavior of the copolymers was lost. This smart polymer response led to disintegration of the supramolecular structures, possibly releasing the therapeutic cargo. By tuning the transition temperature to the values relevant for medical applications, we ensure precise and effective drug release. In addition, our systems did not exhibit any cytotoxicity against any of the three cell lines. Our findings underscore the immense potential of these nanoparticles as eventual advanced drug delivery systems, especially for cancer therapy.

• Klíčová slova
• RAFT polymerization, drug delivery systems, pH-sensitive polymers, self-assembling block copolymers, thermoresponsive polymers,
• MeSH
• biokompatibilní materiály * chemie   chemická syntéza   farmakologie   MeSH
• doxorubicin * farmakologie   chemie   MeSH
• koncentrace vodíkových iontů MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• nanočástice * chemie   MeSH
• polymery * chemie   MeSH
• povrchové vlastnosti MeSH
• protinádorová antibiotika * farmakologie   chemie   MeSH
• screeningové testy protinádorových léčiv MeSH
• teplota MeSH
• testování materiálů MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biokompatibilní materiály * MeSH
• doxorubicin * MeSH
• polymery * MeSH
• protinádorová antibiotika * MeSH

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.

• Klíčová slova
• glycoconjugate, lupane, oleanane, pharmacological effects, saponin, ursane,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

This review comprehensively describes the recent advances in the synthesis and pharmacological evaluation of steroid polyamines squalamine, trodusquemine, ceragenins, claramine, and their diverse analogs and derivatives, with a special focus on their complete synthesis from cholic acids, as well as an antibacterial and antiviral, neuroprotective, antiangiogenic, antitumor, antiobesity and weight-loss activity, antiatherogenic, regenerative, and anxiolytic properties. Trodusquemine is the most-studied small-molecule allosteric PTP1B inhibitor. The discovery of squalamine as the first representative of a previously unknown class of natural antibiotics of animal origin stimulated extensive research of terpenoids (especially triterpenoids) comprising polyamine fragments. During the last decade, this new class of biologically active semisynthetic natural product derivatives demonstrated the possibility to form supramolecular networks, which opens up many possibilities for the use of such structures for drug delivery systems in serum or other body fluids.

• Klíčová slova
• angiogenesis, antibiotic, ceragenine, claramine, diabetes, obesity, squalamine, triterpenoids, trodusquemine,
• MeSH
• antiinfekční látky chemická syntéza   chemie   farmakologie   MeSH
• biologické přípravky chemie   farmakologie   MeSH
• cholestanoly chemie   MeSH
• cholestany chemie   MeSH
• inhibitory angiogeneze chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• neuroprotektivní látky chemická syntéza   chemie   farmakologie   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• spermin analogy a deriváty   chemie   MeSH
• steroidy chemická syntéza   chemie   farmakologie   MeSH
• triterpeny chemická syntéza   chemie   farmakologie   MeSH
• vodní organismy chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• 3-N-1(spermine)-7, 24-dihydroxy-5-cholestane 24-sulfate MeSH Prohlížeč
• antiinfekční látky MeSH
• biologické přípravky MeSH
• ceragenins MeSH Prohlížeč
• cholestanoly MeSH
• cholestany MeSH
• claramine MeSH Prohlížeč
• inhibitory angiogeneze MeSH
• neuroprotektivní látky MeSH
• protinádorové látky MeSH
• spermin MeSH
• squalamine MeSH Prohlížeč
• steroidy MeSH
• triterpeny MeSH

Pentacyclic triterpenes are important representatives of natural products that exhibit a wide variety of biological activities. These activities suggest that these compounds may represent potential medicines for the treatment of cancer and viral, bacterial, or protozoal infections. Naturally occurring triterpenes usually have several drawbacks, such as limited activity and insufficient solubility and bioavailability; therefore, they need to be modified to obtain compounds suitable for drug development. Modifications can be achieved either by methods of standard organic synthesis or with the use of biocatalysts, such as enzymes or enzyme systems within living organisms. In most cases, these modifications result in the preparation of esters, amides, saponins, or sugar conjugates. Notably, while standard organic synthesis has been heavily used and developed, the use of the latter methodology has been rather limited, but it appears that biocatalysis has recently sparked considerably wider interest within the scientific community. Among triterpenes, derivatives of lupane play important roles. This review therefore summarizes the natural occurrence and sources of lupane triterpenoids, their biosynthesis, and semisynthetic methods that may be used for the production of betulinic acid from abundant and inexpensive betulin. Most importantly, this article compares chemical transformations of lupane triterpenoids with analogous reactions performed by biocatalysts and highlights a large space for the future development of biocatalysis in this field. The results of this study may serve as a summary of the current state of research and demonstrate the potential of the method in future applications.

• Klíčová slova
• betulin, betulinic acid, biocatalysis, biotransformation, enzyme, extraction, lupane, lupeol, prodrugs, synthesis,
• MeSH
• biokatalýza * MeSH
• hydrolýza MeSH
• objevování léků MeSH
• oxidace-redukce MeSH
• triterpeny chemická syntéza   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• lupane MeSH Prohlížeč
• triterpeny MeSH

The target diosgenin-betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate 7 showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC50 = 6.5 ± 1.1 µM), in contrast to the conjugate 8 showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition, 5 showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates 3 and 4 showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds.

• Klíčová slova
• ADME parameters, Huisgen copper(I)-catalyzed 1,3-dipolar cycloaddition, adaptogen, betulinic acid, catalytic hydrogenation, conjugate, cytotoxicity, diosgenin,
• MeSH
• cykloadiční reakce MeSH
• diosgenin chemie   MeSH
• hydrogenace MeSH
• katalýza MeSH
• kyselina betulinová MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• palladium chemie   MeSH
• pentacyklické triterpeny chemie   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• screeningové testy protinádorových léčiv MeSH
• tlak MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• diosgenin MeSH
• kyselina betulinová MeSH
• palladium MeSH
• pentacyklické triterpeny MeSH
• protinádorové látky 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.

• Klíčová slova
• ADME parameters, antitumor activity, antiviral activity, betulinic acid, cytotoxicity, physicochemical parameters, structural modification, supramolecular self-assembly,
• MeSH
• chemické jevy * MeSH
• fytonutrienty chemie   izolace a purifikace   farmakologie   MeSH
• kyselina betulinová MeSH
• lidé MeSH
• pentacyklické triterpeny MeSH
• triterpeny chemie   izolace a purifikace   farmakologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fytonutrienty MeSH
• kyselina betulinová MeSH
• pentacyklické triterpeny MeSH
• triterpeny MeSH