The interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles as well as cytisine and salsoline alkaloids were presented in this paper. It was shown that the reaction resulted in ...one one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction was affected by the presence of a base and an order in which reagents were added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity was carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking demonstrated that the compounds had insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increased the affinity of these substrates for target proteins selected.
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. Thus, research is ongoing to find potentially therapeutic AChE inhibitory agents, both from natural and synthetic sources. Here, we synthesized 13 new lupinine triazole derivatives and evaluated them, along with 50 commercial lupinine-based esters of different carboxylic acids, for AChE inhibitory activity. The triazole derivative
1
,9a
)-1-((4-(4-(benzyloxy)-3-methoxyphenyl)-1
-1,2,3-triazol-1-yl)methyl)octahydro-2
-quinolizine) exhibited the most potent AChE inhibitory activity among all 63 lupinine derivatives, and kinetic analysis demonstrated that compound
was a mixed-type AChE inhibitor. Molecular docking studies were performed to visualize interaction between this triazole derivative and AChE. In addition, a structure-activity relationship (SAR) model developed using linear discriminant analysis (LDA) of 11 SwissADME descriptors from the 50 lupinine esters revealed 5 key physicochemical features that allowed us to distinguish active versus non-active compounds. Thus, this SAR model could be applied for design of more potent lupinine ester-based AChE inhibitors.
A series of N-acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested for antimicrobial, antifungal, ...antiviral and analgesic activity. The most pronounced antibacterial activity was shown by the compounds with isoxazole fragments, while the adamantane derivatives showed the greatest antiviral effect. It was found that the majority of anabasine derivatives showed significant analgesic activity, reducing the pain response of animals to the irritating effect of acetic acid. The presence of a high level of antimicrobial and antiviral activity in newly synthesized compounds makes it possible to consider them promising for further study of their pharmacological properties.
An efficient method of producing quinine derivatives via reaction of acylation with 4,5-dichloroisothiazole-3-, 5-arylisoxazole-3-, adamantane- and hydrochlorides of pyridine-3- and ...pyridine-4-carbonyl chlorides was developed. All synthesized compounds were tested for antiviral, antimicrobial and analgesic activity. The most pronounced antibacterial activity was shown by the compounds
,
,
and
with isoxazole and pyridine fragments. It was found that most of the tested compounds showed significant analgesic activity reducing the pain response of animals to the irritating effect of acetic acid.
This article has studied the synthesis of a new derivative of the known alkaloid cytisine contained in the seeds of plants of Cytisus laburnum L. and Thermopsis lanceolata R.Br., both of the ...Lugiminosae family. The new compound has been obtained from two biologically active compounds, such as isoxazole and cytisine. It has been demonstrated that the reaction led to the single-stage method under very mild conditions to obtain 4-(3,5-dimethyl-1,2-oxazol-4-yl)sulfonylcytisine. This class of compounds is promising for obtaining the new biologically active compounds. This article has examined, in detail, a structure with using the
H and
C NMR and two-dimensional NMR spectroscopy of COSY (
H-
H), HMQC (
H-
C) and HMBC (
H-
C). As a result, the homo- and heteronuclear spin-spin couplings should be established. The X-ray diffraction analysis has determined the spatial structure of a new derivative based on the cytisine alkaloid. Thus, its hemorheological activity has been studied.
Modification of the quinolizine backbone of the alkaloid lupinine was carried out by introducing substituted 1,2,3-triazole. When NaN
3
acts upon the product of the reaction of lupinine with ...methanesulfonyl chloride, lupinyl azide is formed which in the reaction with terminal alkynes in the presence of aqueous CuSO
4
and sodium ascorbate forms the corresponding (1
S
,9a
R
)-1-(1,2,3-triazol-1-yl)-methyloctahydro-1
H
-quinolizines with various substituents at the C-4 position of the triazole ring. The structures of lupinine methanesulfonate and 1-(1,2,3-triazol-1-yl)methyloctahydroquinolizines were confirmed by X-ray structural analysis. 1-(1,2,3-Triazol-1-yl)methyloctahydroquinolizines containing a hydroxymethyl or 2-hydroxypropan-2-yl substituent at the C-4 position of the triazole ring exhibit pronounced analgesic activity.
A series of N-acyl derivatives of anabasine and cytisine were prepared, to discover novel, natural product-based medicinal agents. All synthesized compounds were tested for antimicrobial, antifungal, ...antiviral and analgesic activity. The most pronounced antibacterial activity was shown by the compounds with isoxazole fragments, while the adamantane derivatives showed the greatest antiviral effect. It was found that the majority of anabasine derivatives showed significant analgesic activity, reducing the pain response of animals to the irritating effect of acetic acid. The presence of a high level of antimicrobial and antiviral activity in newly synthesized compounds makes it possible to consider them promising for further study of their pharmacological properties.
Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor activity, in ...combination with the commonly used five anticancer drugs, namely cyclophosphane, fluorouracil, etoposide, cisplatin, ribomustine with different mechanisms of action, was investigated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting C6 rat glioma model cells.
There has been presented data on the synthesis of monoamides and cyclic imides which are derivatives of isonicotinic acid hydrazide. Cyclic anhydrides of carboxylic acids (succinic, maleic and ...phthalic) easily react with the hydrazide of isonicotinic acid with cycle opening, forming isonicotinoylhydrazide of dicarboxylic acids, and under more severe conditions the latter are transformed into cyclic acid imides. The structures of the synthesized compounds were studied using 1H- and 13C-NMR spectroscopy, as well as data from twodimensional COSY (1H-1H) and HMQC (1H-13C) spectra. The values of chemical shifts, multiplicity and integral intensity of 1H and 13C signals in one-dimensional NMR spectra were determined. Homo- and heteronuclear interactions confirming the structure of the studied compounds were established using spectra in the COSY (1H-1H) and HMQC (1H-13C) formats. In the approximation of the density functional B3LYP with a base set of 6-31G(d), the enthalpy of the reactions ΔHr in the absence and in the presence of a solvent — isopropanol (self-consistent reaction field method) were calculated quantum-chemically
•Crystal structures of the methanol solvate of 3 and the crystalline hydrate of 5 were analyzed.•Molecules of 3 and 5 mainly stabilized by intermolecular hydrogen bonds more than 95 %.•5 contains two ...independent molecules of 5 with different orientation of ethyl groups in dimethylamine fragment.•5, 9 and 10 showed moderately pronounced activity in the test with the B. subtilis culture.•9 and 10 characterized as the most efficient agents against B. subtilis culture.
The condensation reaction of 4- and 2-hydroxybenzoic acid hydrazides with substituted benzaldehydes led to the formation of a series of hydrazones. The synthesis of hydrazones was carried out successfully in good yields. The structure of compounds was proved by spectral methods. The crystal structures of the methanol solvate of the (E)-N’-4-(diethylamino)-benzylidene-4-hydroxybenzohydrazide and the crystalline hydrate of the (E)-N’-(2‑hydroxy-4-diethylamino)-benzylidene-4-hydroxybenzohydrazide were described with attention to conformational features and hydrogen bonding. The antimicrobial and antiradical activity of hydrazones was studied using molecular docking and in vitro assays.
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