Synthesis and exploration of anticancer potential of spirocyclic 1,2,3-triazoline and aziridine derivatives of natural eudesmanolide isoalantolactone.

Eudesmane-type sesquiterpene lactone isoalantolactone 1 is of great interest due to its availability, biological activity and synthetic application. Respective series of original spirocyclic (11S,5') (1,2,3-triazoline-eudesma-4,15-enolides) and (11S)-aziridine-eudesma-4,15-enolides were efficiently synthesized via a chemoselective 1,3-dipolar cycloaddition reaction of organic azides to the exocyclic double bond of the lactone ring of isoalantolactone or 13E-(aryl)isoalantolactones by heating in DMF or toluene. The thermal reactions of isoalantolactone with benzyl azide, 2-azidoethanol, or n-butyl azide in 2-methoxyethanol afforded 13-(alkyamino)isoalantolactones formed as a mixture of (Z) and (E)-isomers.

Antiviral Activity of (1,9a)-1-[(1,2,3-Triazol-1-yl)methyl]octahydro-1-quinolizines from the Alkaloid Lupinine.

Influenza is a disease of significant morbidity and mortality. The number of anti-influenza drugs is small; many of them stimulate the appearance of resistant strains. This article presents the results of assessing the antiviral activity of 1,2,3-triazole-containing derivatives of alkaloid lupinine for their ability to suppress the reproduction of orthomyxoviruses (influenza viruses: A/Vladivostok/2/09 (H1N1) and A/Almaty/8/98 (H3N2)).

Synthesis and anticancer evaluation of new lupane triterpenoid derivatives containing various substituent at the 2 or 3 position.

Betulonic acid benzyl ester 1 has been subjected to a series of structural modifications for the purpose of new triterpenoid synthesis and evaluating for anticancer activity. The one-pot two step synthesis of 2α-(aminomethyl)betulinic acid benzyl ester derivatives 3a-f (yield 46-69 %) was achieved by the Mannich reaction of compound 1 with methyleneiminium salts, generated in situ from N,N-disubstituted bis(amino)methanes 2a-f by the action of acetyl chloride in dichloromethane, and subsequent reduction of aminomethylation products with sodium borohydride. Minor 2β-(aminomethyl) triterpenoids 4c,d,f were also isolated (yield 6-15 %).

Biological effects and phytochemical study of the underground part of Iris scariosa Willd. ex Link extract: A new source of bioactive constituents.

The expected toxicity and resistance of chemotherapeutic agents necessitate and encourage for the use of natural chemotherapeutic sources of plant origin in the clinical stage of cancer therapy. Plants of the genus Iris (Iridaceae) used by local populations for the treatment of cancer, bacterial and viral infections. In this study, an ethanol extract of rhizomes of I.

Hepatotropic activity of a betulonic acid based compound.

Using the model of cyclophosphamide (CP)-induced immunosuppression in C57BL/6 mice, the hepatotropic effects of a conjugate of betulonic acid with 9-(4-methylpiperazin-1-ylmethyl)-2-(1,2,3-triazolyl) oreozelone (BABC) have been studied. In the liver of treated animals the expression of genes for cytochromes (CYP 1A1, CYP 1A2, CYP 3A44, CYP 2B10, CYP 2C29, CYP 17A1), PPARA, and cytokines (TNF-α, IL-1β, IL-12α, IL-10) and the relative levels of NF-κB p65, GST-π, and NAT-1 proteins were determined. On day six after administration of the compound and CP to animals a significant (3.

Synthesis, Pharmacological Evaluation, and Molecular Modeling of Lappaconitine-1,5-Benzodiazepine Hybrids.

Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, have long interested scientists due to their medicinal uses and infamous toxicity which has limited the clinical application of the native compound. Alkaloid lappaconitine extracted from various and species has displayed extensive bioactivities and active ongoing research to reduce its adverse effects. A convenient route to construct hybrid molecules containing diterpenoid alkaloid lappaconitine and 3-1,5-benzodiazepine fragments was proposed.

Inhibition of Acetylcholinesterase by Novel Lupinine Derivatives.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment due in part to a severe loss of cholinergic neurons in specific brain areas. AD is the most common type of dementia in the aging population. Although several acetylcholinesterase (AChE) inhibitors are currently available, their performance sometimes yields unexpected results.

Design, Synthesis and Assay of Novel Methylxanthine-Alkynylmethylamine Derivatives as Acetylcholinesterase Inhibitors.

Xanthine derivatives have been a great area of interest for the development of potent bioactive agents. Thirty-eight methylxanthine derivatives as acetylcholinesterase inhibitors (AChE) were designed and synthesized. Suzuki-Miyaura cross-coupling reactions of 8-chlorocaffeine with aryl(hetaryl)boronic acids, the CuAAC reaction of 8-ethynylcaffeine with several azides, and the copper(I) catalyzed one-pot three-component reaction (A-coupling) of 8-ethynylcaffeine, 1-(prop-2-ynyl)-, or 7-(prop-2-ynyl)-dimethylxanthines with formaldehyde and secondary amines were the main approaches for the synthesis of substituted methylxanthine derivatives (yield 53-96%).

Radiological biomarkers of brain gliomas.

The most important objective of modern neuroimaging is comparison of data on genotype and phenotype of brain gliomas. Radiogenomics as a new branch of science is devoted to searching for such relationships based on MRI and PET/CT parameters. The 2021 WHO classification of tumors of the central nervous system poses the most important tasks for physicians in assessment of biological behavior of tumors and their response to combined treatment.

Synthesis of fully functionalized spirostanic 1,2,3-triazoles by the three component reaction of diosgenin azides with acetophenones and aryl aldehydes and their biological evaluation as antiproliferative agents.

Diosgenin is of significant interest due to its biological activity and synthetic application. In this study, we report the synthesis of a series of spirostanic 1,4,5-trisubstituted 1,2,3-triazoles by the three component reaction of (25R)-6-azidospirostan-3,5-diols with acetophenones and aryl aldehydes. The one-pot two step synthesis proceeds through the in situ formation of (E)-chalcones and copper catalyzed reaction with organic azides in DMF medium.

Conjugates of Lupane Triterpenoids with Arylpyrimidines: Synthesis and Anti-inflammatory Activity.

Semisynthetic triterpenoid betulonic acid is of significant interest due to its biological activity and synthetic application. In this study, we report the synthesis of hybrid compounds, containing betulonic acid carboxamide and arylpyrimidine fragments. A total of 15 conjugates were prepared using the cyclocondensation reaction of new terpenoid alkynyl ketones with amidinium salts.

An Approach toward 17-Arylsubstituted Marginatafuran-Type Isospongian Diterpenoids via a Palladium-Catalyzed Heck-Suzuki Cascade Reaction of 16-Bromolambertianic Acid.

Isospongian diterpenes are a small but growing family of natural tetracyclic secondary metabolites isolated from marine organisms, primarily sponges and nudibranchs. A palladium-catalyzed domino Heck-Suzuki reaction sequence for the synthesis of the tetracyclic skeleton of marginatafuran-type isospongian diterpenoids with a wide variety of substituents in the C-17 position is reported. The proposed approach was based on selective transformations of the accessible plant diterpenoid lambertianic acid and includes an intramolecular Heck reaction of 16-bromolambertianic and arylation of the palladium intermediate with arylboronic acid.

Synthesis of Anti-Inflammatory Spirostene-Pyrazole Conjugates by a Consecutive Multicomponent Reaction of Diosgenin with Oxalyl Chloride, Arylalkynes and Hydrazines or Hydrazones.

Steroid sapogenin diosgenin is of significant interest due to its biological activity and synthetic application. A consecutive one-pot reaction of diosgenin, oxalyl chloride, arylacetylenes, and phenylhydrazine give rise to steroidal 1,3,5-trisubstituted pyrazoles (isolated yield 46-60%) when the Stephens-Castro reaction and heterocyclization steps were carried out by heating in benzene. When the cyclization step of alkyndione with phenylhydrazine was performed in 2-methoxyethanol at room temperature, steroidal α,β-alkynyl ()- and ()-hydrazones were isolated along with 1,3,5-trisubstituted pyrazole and the isomeric 2,3,5-trisubstituted pyrazole.

Phase 3 trial of coronavir (favipiravir) in patients with mild to moderate COVID-19.

Favipiravir has demonstrated efficacy against the SARS-CoV-2 virus in several preliminary studies. This study aimed to evaluate the efficacy and safety of favipiravir for treatment of mild to moderate COVID-19 in outpatients and hospitalized patients. We conducted an open-label, randomized, active-controlled trial of a generic form of favipiravir in patients with COVID-19 confirmed by PCR-test.

[Lessons learnt from 101 hemispheric pediatric epilepsy surgeries part ii: pitfalls and complications].

Objective: To evaluate the spectrum of pitfalls and complications after hemisherotomy basing on a retrospective study of a large consecutive pediatric cohort of patients from a single institution.

Material And Methods: One hundred and one patients (med. age - 43 months) with refractory seizures underwent hemispherotomy.

[Lessons learnt from 101 hemispherotomies in children with symptomatic epilepsy. Part I: seizure outcome].

Objective: To evaluate variables that may predict the outcome after hemispherotomy basing on a retrospective study of a large consecutive pediatric cohort of patients from a single institution.

Material And Methods: One hundred and one patients with refractory seizures and variable decline in development (=78) underwent hemispherotomy (med. age - 43 months, med.

Multiple hippocampal transections for mesial temporal lobe epilepsy.

Background: The purpose of this study was to evaluate the effectiveness of multiple hippocampal transections (MHT) in the treatment of drug-resistant mesial temporal lobe epilepsy.

Methods: Six patients underwent MHT at Burdenko Neurosurgery Center in 2018. The age of the patients varied from 18 to 43 years.

[Anaplastic astrocytoma and anaplastic oligodendroglioma of the brain: current state of the problem].

This review is devoted to the problem of anaplastic cerebral gliomas. The authors consider classification, neuroimaging of these tumors including comparison of magnetic resonance imaging and positron emission tomography data. Clinical manifestations of anaplastic gliomas, issues of their histological and molecular genetic classification are discussed.

Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo.

Calcium chelidonate [Ca(ChA)(HO)] was obtained by semi-synthesis using natural chelidonic acid. The structure of the molecular complex was determined by X-ray diffraction analysis. The asymmetric unit of [Ca(ChA)(HO)] includes chelidonic acid coordinated through three oxygen atoms, and three water ligands.

Design and linkage optimization of ursane-thalidomide-based PROTACs and identification of their targeted-degradation properties to MDM2 protein.

Ursolic acid (UA) is an accessible triterpenoid, widely applied in the design and synthesis of antitumor compounds. However, the mechanism of its anti-tumor effect is still unclear. To verify the molecular mechanism of its biological activity, based on the bifunctional activity of ubiquitination and subsequent proteasomal degradation of the target protein of the proteolysis-targeting chimeras (PROTACs) strategy, here we report the design, synthesis and cellular activity of six UA PROTAC hydrochloride compounds 1A-1F, in which UA acts as the binding ligand of the PROTAC and is linked to thalidomide (E3 ligand) through a series of synthetic linkers.

[Intracellular pH measurement in glioblastoma cells: the possibilities of phosphorus-31 MR spectroscopy].

Objective: To analyze intracellular pH measurement with phosphorus-31 MR spectroscopy in glioblastoma cells and to compare these data with intracellular pH in healthy volunteers.

Material And Methods: There were 10 patients aged 41 - 67 years with supratentorial glioblastomas. Intracellular pH in glioblastoma cells was compared with pH in healthy persons.

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency.

Convenient and efficient routes to construct hybrid molecules containing diterpene alkaloid lappaconitine and pyrimidine fragments are reported. One route takes place via first converting of lappaconitine to 1-ethynyl-lappaconitine, followed by the Sonogashira cross-coupling-cyclocondensation sequences. The other involves the palladium-catalyzed carbonylative Sonogashira reaction of 5'-iodolappaconitine with aryl acetylene and Mo (CO) as the CO source in acetonitrile and subsequent cyclocondensation reaction of the generated alkynone with amidines.

[Surgical treatment of epilepsy in children with focal cortical dysplasia].

Objective: Surgery is the first-line treatment option in children with FCD and refractory epilepsy, but the rate of success and patient numbers who became free of seizures vary widely from series to series.

Study Aims: To elicit variables affecting the outcome and predicting achievement of the long-term seizure-free status.

Material And Methods: One hundred sixty-nine children with cortical dysplasia and DR-epilepsy underwent surgery Preoperative evaluation included prolonged video-EEG and MRI (in all patients) and neuropsychological testing when possible.