Assessing the inhibitory effects of some secondary amines, thioureas and 1,3-dimethyluracil conjugates of (-)-cytisine and thermopsine on the RNA-dependent RNA polymerase of SARS-CoV-1 and SARS-CoV-2.

SARS-CoV-2 causes COVID-19, with symptoms ranging from mild to severe, including pneumonia and death. This beta coronavirus has a 30-kilobase RNA genome and shares about 80 % of its nucleotide sequence with SARS-CoV-1. The replication/transcription complex, essential for viral RNA synthesis, includes RNA-dependent RNA polymerase (RdRp, nsp12) enhanced by nsp7 and nsp8.

Inhibition of dengue viruses by N-methylcytisine thio derivatives through targeting viral envelope protein and NS2B-NS3 protease.

Dengue virus (DENV) is a significant global health threat, causing millions of cases worldwide each year. Developing antiviral drugs for DENV has been a challenging endeavor. Our previous study identified anti-DENV properties of two (-)-cytisine derivatives contained substitutions within the 2-pyridone core from a pool of 19 (-)-cytisine derivatives.

Synthesis and cytotoxic activity of some (+)-salsolidine derivatives.

On the basis of typical for secondary amino group reactions a number of derivatives of alkaloid (+)-salsolidine was synthesised. Cytotoxic properties of obtained compounds towards the HEK293, A549, MCF-7 and SH-SY5Y cell lines have been evaluated. As a result of the screening, the hit compound - 2-(chloroacetyl)-6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline () was identified, that inhibited the metabolic activity of A-549, MCF-7 and SH-SY5Y tumour cell lines with the IC values of 3.

Synthesis and antiviral evaluation of cytisine derivatives against dengue virus types 1 and 2.

Dengue virus (DENV) causes about 50-100 million cases per year worldwide. However, there is still a big challenge in developing antiviral drugs against DENV infection. Some derivatives of alkaloid (-)-cytisine, like other alkaloid analogs, have been proposed for their antiviral potential.

Thionation of quinolizidine alkaloids and their derivatives via Lawesson's reagent.

Direct thionation of quinolizidine alkaloids (-)-cytisine, methylcytisine, thermopsine and some of their carbonyl derivatives was realized. It was established that carrying out of the reaction in the boiling toluene with 0.5 eq.

Antiviral activity of amides and carboxamides of quinolizidine alkaloid (-)-cytisine against human influenza virus A (H1N1) and parainfluenza virus type 3.

Novel derivatives of quinolizidine alkaloid ()-cytisine were synthesised. ADME properties, cytotoxicity against HEK293 cells and activity against viruses of influenza A/California/07/09(H1N1)pdm09 virus (IAV) and human parainfluenza virus type 3 (HPIV3) were evaluated. It was shown, that 9-carboxamides of methylcytisine (with phenyl and allyl urea's fragments) are most active compounds against IAV probably due to predicted peculiarity of their interactions with the 4R7B active site of IAV neuraminidase.

Variation of spacer type and topology of phenyl moiety in 2-pyridone core of 4-oxo-3--methylcytisine; effect of synthesized compounds on rat's behavior in conditioned passive avoidance reflex (CPAR) test.

Novel derivatives of 4-oxo-3-methylcytisine with phenyl moiety bonded to starting molecule through various spacers were obtained from the 9-amino, -halo, -formyl and 11-halo precursors by reductive alkylation of amines, generation of amide, as well as thio- and carboxamide functions, cross-coupling reactions, aldehyde condensation and reduction of unsaturated 'C-C' bonds. Ability of synthesized compounds to influence the learning and memory was preliminary assessed in conditioned passive avoidance reflex (CPAR) test in rats. It was shown, that derivatives with phenyl group at 11 carbon atom influence the learning and memory in CPAR test more effectively than other compounds.

Direct formylation of 2-pyridone core of 3--methylcytisine via Duff reaction; synthesis of 9-enyl, 9-ynyl and 9-imino derivatives.

The first direct synthesis of 3--methyl-9-formylcytisine via electrophylic formylation is described. It is established, that Vilsmeier-Haack and Gatterman variants of this reaction are unsuccessful in the case with 3-substituted (-)-cytisine derivatives, but Duff procedure (with hexamethylenetetramine in trifluoroacetic acid) gives a possibility to obtain the target pseudo aromatic aldehyde with the 69% yield. Convenient precursors for [4 + 2]- or [3 + 2]-cycloaddition reactions are obtained by means of condensation of synthesized 3--methyl-9-formylcytisine with acetone, nitromethane and phosphorous ylides with yields from 70 to 87%.

Nootropic Activity of a Novel (-)-Cytisine Derivative (3aR,4S,8S,12R, 12aS,12bR)-10-Methyl-2-Phenyloctahydro-1H-4,12a-Etheno-8,12-Methanopyrrolo[3',4':3,4]Pyrido[1,2-a] [1,5]Diazocine-1,3,5(4H)-Trione.

We performed screening of nootropic properties of 10 new derivatives of quinolizidine alkaloid (-)-cytisine. Compounds with β-endo stereochemistry were more active than α-endo-isomers. Under stress conditions (3aR,4S,8S,12R,12aS,12bR)-10-methyl-2-phenyloctahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3',4':3,4]pyrido[1,2-a] [1,5]diazocine-1,3,5(4H)-trione enhanced memory and had a positive effect on cognitive functions of rats.

Anti-Inflammatory Activity of Novel 12-N-methylcytisine Derivatives.

Background And Objectives: Neurodegenerative diseases and inflammation are always linked to each other; therefore the elaboration of new chemical compounds, which interact with pharmacological targets involved into these two processes, can become one of ways of correction of these types of human CNS pathology. In the field of this problem the anti-inflammatory activity of ten 3-amino derivatives of quinolizidine alkaloid (.)-cytisine (the data about nootropic activity of these compounds are outlined by us previously) was studied by using in vivo, in vitro and in silico approaches.

Aza-Michael reaction of 12-N-carboxamide of (-)-cytisine under high pressure conditions.

The first example of aza-Michael reaction of 12-N-carboxamide of quinolizidine alkaloid (-)-cytisine with α,β-unsaturated ketones, dimethyl acetylenedicarboxylate and β-nitrostyrene under high pressure condition has been described. It has been shown that the [4+2]-cycloaddition takes place in the case with N-phenylmaleimide.