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 (1H NMR, 13C NMR, and FT-IR), mass spectrometry, and the PM5 semiempirical method. The synthesized compounds' pharmacotherapeutic potential has been evaluated, employing the Prediction of Activity Spectra for Substances (PASS) methodology. Additionally, molecular docking was performed for all molecules.

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 (1H- and 13C 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. According to molecular docking studies, the tested ligands are highly likely to exhibit a similar affinity, as native ligands, for the active sites of specific protein domains (PDB IDs: 2Q85 and 5V5Z). The obtained results may be helpful for the development of selective bile acid bioconjugates as effective antibacterial, antifungal, or antioxidant agents.

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. These compounds were then converted to azide derivatives using sodium azide. The propiolic esters of lithocholic, deoxycholic and cholic acids were obtained by reaction with propiolic acid in the presence of p-toluenesulfonic acid. Additionally, two of these steroids: methyl 3α-propynoyloxy-12α-acetoxy-5ß-cholane-24-oate and methyl 3α-propynoyloxy-7 α,12α-diacetoxy-5ß-cholane-24-oate were also obtained and characterized for the first time. All conjugates were obtained in good yields using an efficient synthesis method. The structures of all conjugates and the four substrates were confirmed by spectral (1H- and 13C NMR, FT-IR) analysis, mass spectrometry (ESI-MS), and PM5 semiempirical methods. The pharmacotherapeutic potential of the synthesized compounds was estimated based on the in silico Prediction of Activity Spectra for Substances (PASS) method. The cytotoxicity of the compounds was in vitro evaluated in a hemolytic assay using human erythrocytes as a cell model. The in silico and in vitro study results indicate that the selected compound possesses an interesting biological activity and can be considered as potential drug design agent. Additionally, molecular docking was performed for the selected conjugate.

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. All conjugates were obtained in good yields using an efficient synthesis method. The structures of all products were confirmed by spectral (1H- and 13C NMR, and FT-IR) analysis, mass spectrometry (ESI-MS), as well as PM5 semiempirical methods. Estimation of the pharmacotherapeutic potential has been accomplished for the synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS).

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, 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 3ß-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. Estimation of the pharmacotherapeutic potential has been accomplished for synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS).

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. Estimation of the pharmacotherapeutic potential has been accomplished for synthesized compounds on the basis of Prediction of Activity Spectra for Substances (PASS).

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).

A novel synthetic approach to (20R)- and (20S)-21-hydroxy steroids. Synthesis of a marine sterol 21-hydroxycholesterol.

A short and efficient synthesis of steroid synthons, di(tert-butyldimethylsilyl) ethers of 3,21-dihydroxy-24-nor-chol-5-en-23-al (8 and 10) and of ethyl 3,21-dihydroxy-25-homo-chola-5,23-dien-25-oate (9 and 11), having natural (20R) and unnatural (20S) configuration from 3ß-(tert-butyldimethylsilyloxy)-14α,20ξ-card-5-enolide (2) is reported. Further elongation of the side chain of these synthons provides a new method for the synthesis of (20R) and (20S)-21-hydroxy steroids. The utility of the method was exemplified by the synthesis of a natural marine sterol - 21-hydroxycholesterol (18).

Two isomeric cucurbitane derivatives.

Two isomeric cucurbitane derivatives, 3beta,7alpha,11beta-triacetoxycucurbit-5(10)-ene, (I), and 3beta,7alpha,11beta-triacetoxy-5alpha-cucurbit-1(10)-ene, (II), both C(36)H(58)O(6), have their single endocyclic C=C double bonds in different positions. This results in differences in the conformation of the four-ring system, which is close to a half-chair/half-chair/chair/half-chair arrangement in (I) and to a half-chair/twist-boat/boat/half-chair arrangement in (II). The orientation of some of the substituents is also different; the 3beta-acetoxy group is in an equatorial position in (I) but in an axial position in (II), while the 11beta-acetoxy group occupies an axial position in (I) and an equatorial position in (II). The asymmetric unit of (I) contains two symmetry-independent molecules which do not differ significantly, being related by a pseudo-twofold axis of symmetry. In both structures, the aliphatic chain fragments are disordered and the disorder persists at lower temperatures.