Steroid and bioactive molecule conjugates: Improving therapeutic approaches in disease management.

Conjugates of steroids and other natural bioactive molecules (such as amino acids or carbohydrates) have proven promising compounds with diverse biological effects. This literature review summarises the importance of steroid conjugates in a broad spectrum of therapeutic applications. Steroid conjugates exhibit improved pharmacokinetic properties, improved target specificity, and reduced side effects compared to the parent compounds.

Synthesis, Hemolytic Activity, and In Silico Studies of New Bile Acid Dimers Connected with a 1,2,3-Triazole Ring.

The synthesis of bile acid conjugates plays a significant role in pharmacology and organic chemistry. These complex compounds are widely studied due to their potential therapeutic applications (e.g.

Exploring Triazole-Connected Steroid-Pyrimidine Hybrids: Synthesis, Spectroscopic Characterization, and Biological Assessment.

Molecules originating from natural sources are physicochemically and biologically diverse. The conjugation of two active biomolecules has become the foundation for medical and pharmaceutical sciences. An effective synthesis of 11 new steroid-pyrimidine conjugates containing 1,2,3-triazole rings was carried out.

Quasi-Podands with 1,2,3-Triazole Rings from Bile Acid Derivatives: Synthesis, and Spectroscopic and Theoretical Studies.

An innovative approach to producing derivatives of bile acids has been devised, utilizing the principles of "click" chemistry. By employing intermolecular [3 + 2] cycloaddition between the newly developed acyl propiolic esters of bile acids and the azide groups of 1,3,5-tris(azidomethyl)benzene, a novel class of quasi-podands featuring 1,2,3-triazole rings has been synthesized. Identifying and characterizing these six compounds involved comprehensive analysis through spectral techniques (H NMR, C NMR, and FT-IR), mass spectrometry, and the PM5 semiempirical method.

Synthesis and Hemolytic Activity of Bile Acid-Indole Bioconjugates Linked by Triazole.

New formyl and acetyl derivatives of bile acid propargyl esters and their bioconjugates with modified gramine molecules have been obtained using the click chemistry method to study their hemolytic potency. The structures of all compounds were confirmed by spectral (H- and C NMR and FT-IR) analysis and mass spectrometry (ESI-MS) as well as PM5 semiempirical methods. According to the results, the structural modification of formyl and acetyl bile acid derivatives, leading to the formation of new propargyl esters and indole bioconjugates, reduces their hemolytic activity.

Click chemistry as a method for the synthesis of steroid bioconjugates of bile acids derivatives and sterols.

Six steroid conjugates of bile acids and sterol derivatives have been synthesized using the click chemistry method. The azide-alkyne Huisgen cycloaddition of the propionyl ester of lithocholic, deoxycholic and cholic acid with azide derivatives of cholesterol and cholestanol gave new bile acid-sterol conjugates linked with a 1,2,3-triazole ring. Previously, sterols were converted to bromoacetate substituted derivatives by reaction with bromoacetic acid bromide in anhydrous dichloromethane.

Design, synthesis, spectral and theoretical study of new bile acid-sterol conjugates linked via 1,2,3-triazole ring.

New four steroid conjugates have been prepared from bile acids and sterol derivatives using click chemistry method. The azide-alkyne Huisgen cycloaddition (intermolecular 1,3-dipolar cycloaddition) of the propargyl ester of lithocholic, deoxycholic, cholic acid as well as dehydrocholic acids and azide derivatives of cholesterol gave a new bile acid-sterol conjugates linked with a 1,2,3-triazole ring. Previously, bile acids were converted into bromoacetyl substituted derivatives by the reaction of propargyl esters of lithocholic, deoxycholic, cholic with bromoacetic acid bromide in toluene with TEBA and sodium hydride.

Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives.

A series of fifteen indole derivatives substituted at the C-3 position were synthesized and characterized. The antioxidant activity of all derivatives was investigated by three in vitro antioxidant assays, and the derivative with pyrrolidinedithiocarbamate moiety was the most active as a radical scavenger and Fe-Fe reducer. It can be stated that possible hydrogen and electron transfer mechanism is suggested for the quenching of the free radical.

Mass Spectrometry Study of New Polyamine Derivatives of Caffeine.

The mass spectrometric fragmentations of ten new 8-alkylaminocaffeine derivatives were investigated. The fragmentation pathways of new polyamine derivatives of caffeine on the basis of low and high-resolution electron ionization (EI) mass spectra were discussed. In the case of new compounds, classical fragmentation of purine skeleton related to the elimination of a neutral molecule CH3N(1)C(2)O from a molecular ion was not observed.

Synthesis, Structure, Surface and Antimicrobial Properties of New Oligomeric Quaternary Ammonium Salts with Aromatic Spacers.

New dimeric, trimeric and tetrameric quaternary ammonium salts were accomplished by reaction of tertiary alkyldimethyl amines with appropriate bromomethylbenzene derivatives. A series of new cationic surfactants contain different alkyl chain lengths (C4-C18), aromatic spacers and different numbers of quaternary nitrogen atoms. The structure of the products was confirmed by spectral analysis (FT-IR, ¹H-NMR, C-NMR and 2D-NMR), mass spectroscopy (ESI-MS), elemental analysis, as well as PM5 semiempirical methods.

Haemolytic activity of formyl- and acetyl-derivatives of bile acids and their gramine salts.

Bile acids (lithocholic: LCA, deoxycholic: DCA and cholic: CA) and their formyl- and acetyl-derivatives can be used as starting material in chemical synthesis of compounds with different biological activity strongly depended on their chemical structures. Our previous studies showed that biological activity of bile acids salts with gramine toward human erythrocytes was significantly different from the activity of bile acids alone. Moreover, gramine effectively modified the membrane perturbing activity of other steroids.

Quaternary Alkylammonium Conjugates of Steroids: Synthesis, Molecular Structure, and Biological Studies.

The methods of synthesis as well as physical, spectroscopic (¹H-NMR, 13C-NMR, and FT-IR, ESI-MS), and biological properties of quaternary and dimeric quaternary alkylammonium conjugates of steroids are presented. The results were contrasted with theoretical calculations (PM5 methods) and potential pharmacological properties (PASS). Alkylammonium sterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.

Spectroscopic methods and theoretical studies of bromoacetyl substituted derivatives of bile acids.

The structure of seven bromoacetic substituted derivatives of bile acids are characterized by 1H MMR, 13C NMR, 2D NMR, FT-IR and mass spectrometry (ESI-MS) as well as PM5 semiempirical and B3LYP ab initio methods. Estimation of the pharmacotherapeutic potential has been accomplished for the synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS).

Synthesis, spectroscopy, theoretical and biological studies of new gramine-steroids salts and conjugates.

New gramine connections with bile acids (lithocholic, deoxycholic, cholic) and sterols (cholesterol, cholestanol) were synthesized. The structures of products were confirmed by spectral (NMR, FT-IR) analysis, mass spectrometry (ESI-MS) as well as PM5 semiempirical methods. Unexpectedly, the products of the reaction of gramine with cholesterol and cholestanol were symmetrical compounds consisting of two molecules of sterols connected by N(CH3)2 group.

Synthesis, spectroscopic and theoretical studies of new dimeric quaternary alkylammonium conjugates of sterols.

New dimeric quaternary alkylammonium conjugates of sterols were obtained by two step reactions of ergosterol, cholesterol and cholestanol with bromoacetic acid bromide, followed by bimolecular nucleophilic substitution with N,N,N',N'-tetramethyl-1,3-propanediamine, N,N,N',N'',N''-pentamethyldiethylenetriamine and 3,3'-iminobis- (N,N-dimethylpropylamine). The product structures were confirmed by spectral (1H-NMR, 13C-NMR, FT-IR) analysis, mass spectrometry (ESI-MS) and PM5 semiempirical methods. Additionally in silico studies have been conducted for the synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS).

Synthesis, spectroscopic and theoretical studies of new quaternary N,N-dimethyl-3-phthalimidopropylammonium conjugates of sterols and bile acids.

New quaternary 3-phthalimidopropylammonium conjugates of steroids were obtained by reaction of sterols (ergosterol, cholesterol, cholestanol) and bile acids (lithocholic, deoxycholic, cholic) with bromoacetic acid bromide to give sterol 3β-bromoacetates and bile acid 3α-bromoacetates, respectively. These intermediates were subjected to nuclephilic substitution with N,N-dimethyl-3-phthalimidopropylamine to give the final quaternary ammonium salts. The structures of products were confirmed by spectral (1H-NMR, 13C-NMR, and FT-IR) analysis, mass spectrometry (ESI-MS, MALDI) as well as PM5 semiempirical methods and B3LYP ab initio methods.

Synthesis, spectroscopic and theoretical studies of new quasi-podands from bile acid derivatives linked by 1,2,3-triazole rings.

A novel method for the synthesis of bile acid derivatives has been developed using "click chemistry". Intermolecular 1,3-dipolar cycloaddition of the propargyl ester of bile acids and azide groups of 1,3,5-tris(azidomethyl)benzene gave a new quasi-podands with 1,2,3-triazole rings. The structures of the products were confirmed by spectral (1H-NMR, 13C-NMR, and FT-IR) analysis, mass spectrometry and PM5 semiempirical methods.

Mass spectrometry of bis-quinolizidine alkaloids: unexpected dimerization in electron ionization mass spectrometry.

The electron-ionization mass spectra of dimers of bis-quinolizidine alkaloids: a-isosparteine, 2-methylsparteine, 17-hydroxylupanine, lupanine N-oxide and 2,17-dimethylsparteine are discussed and general fragmentation routes of their molecular cations are proposed. Dimers structures are also studied using PM5 methods. The recognition of the fragmentation pathways and relative abundances of the ions obtained will provide important information, useful for the identification of similar dimeric compounds.

Synthesis, spectroscopic and semiempirical studies of new quaternary alkylammonium conjugates of sterols.

New quaternary alkylammonium conjugates of steroids were obtained by two step reaction of sterols (ergosterol, cholesterol, dihydrocholesterol) with bromoacetic acid bromide, followed by bimolecular nucleophilic substitution with a long chain tertiary alkylamine. The structures of products were confirmed by spectral (1H-NMR, 13C-NMR, and FT-IR) analysis, mass spectrometry and PM5 semiempirical methods. The pharmacotherapeutic potential of synthesized compounds has been estimated on the basis of Prediction of Activity Spectra for Substances (PASS).

Thio Analogs of Pyrimidine Bases: Synthesis, Spectroscopic Study, and In Silico Biological Activity Evaluation of New 2-o-(m- and p-)Chlorobenzylthio-6-Methyl-5-Piperidino-(Morpholino-)Methyluracils.

Six new 2-o-(m- and p-)chlorobenzylthio-6-methyl-5-piperidino-(or morpholino-) methyluracils have been prepared. The structures of these compounds were confirmed by spectroscopic (FT-IR, UV-Vis, (1)H NMR, (13)C NMR, and HMBC) and elemental analyses. Estimation of pharmacotherapeutic potential has been made for synthesized compounds on the basis of prediction of activity spectra for substances (PASS).

Differentiation of the isomeric o-(m- and p-)nitro-(chloro- and bromo-)benzyl-2,4-(and 2,1-) disubstituted 2-thiocytosinium halides by electron impact ionisation and fast atom bombardment mass spectrometry.

Electron ionisation (EI) and fast atom bombardment (FAB) mass spectral fragmentations of nine 2,4-(and 2,1-) disubstituted o-(m- and p-)nitro-(chloro- and bromo-)-2-thiocytosinium halides are investigated. Fragmentation pathways, whose elucidation is assisted by accurate mass measurements and metastable transitions [EI-mass spectrometry (MS)], as well as FAB/collision-induced dissociation (CID) mass spectra measurements are discussed. The correlations between the abundances of the (C(11)H(10)N(4)SO(2))(+) 1-3; (C(11)H(10)N(3)SCl)(+) 4-6 and (C(11)H(10)N(3)SBr)(+) 7-9 ions and the selected fragment ions (EI- MS), as well as (C(18)H(16)N(5)SO(4))(+) 1-3; (C(18)H(16)N(3)SCl(2))(+) 4-6 and (C(18)H(16)N(3)SBr(2))(+) 7-9 ions and the selected ions (C(7)H(6)NO(2))(+) 1-3; (C(7)H(6)Cl)(+) 4-6; (C(7)H(6)Br)(+) 7-9 (FAB-MS) are discussed.