Acrylic Acid Derivatives Research Articles

Synthesis of N-Alkyl-3-[2-oxoquinolin-1(2H)-yl]propanoic Acid Derivatives and Related Compounds: Cytotoxicity and EGFR Inhibition of Some Propanamide Derivatives.

A series of 20 new structure-modified quinolin-2-one derivatives were prepared for biological evaluation. This was successfully achieved based on chemoselective reactions of heterocyclic amides with acrylic acid derivatives, which gave 3-[2-oxoquinolin-1-(2H)-yl] propanoic acid derivatives (N-substitution via a unique behavior). The ester was reacted with hydrazine to afford the corresponding hydrazide. Both the corresponding ester and hydrazide were used as building blocks to modify the quinolone structure and give N-hydroxyl propanamides, oxadiazoles, and thiosemicarbazides. The corresponding carboxylic acid and hydrazide were used to prepare several amides: N-alkyl-3-[2-oxoquinolin-1(2H)-yl]propanamides via azide and dicyclohexyl carbodiimide coupling methods. Among derivatives, compound 9e exhibited potent cytotoxicity against MCF-7 cells with an IC50 value of 1.32 μM compared to doxorubicin with an IC50 value of 1.21 μM. Additionally, it caused potent EGFR inhibition by 97% with an IC50 value of 16.89 nM compared to Erlotinib with an IC50 value of 29.8 nM. Finally, the binding mode of compound interactions toward EGFR was highlighted using a molecular docking study; compound 9e exhibited good binding affinity with a binding energy of -17.89 kcal/mol, and it formed H-bond interactions with Met 769 as the key amino acid of interaction. Accordingly, compound 9e may be developed as an EGFR-oriented chemotherapeutic antibreast cancer agent.

Myrcene-itaconate Diels-Alder cycloadducts in the synthesis of photocurable polyesters for the 3D printing of fully biobased resins

Photopolymerization-based 3D printing techniques, such as vat photopolymerization (VP), unfortunately still strongly rely on the use of fossil-based (meth)acrylate monomers for the formulation of photo hardening resins. Because of that many researchers have recently directed their efforts towards the replacement of methacrylic and acrylic acid derivatives with biobased counterparts. Indeed, in this work, we introduce a novel approach for producing sixteen fully biobased resins for VP, based on photocurable polyesters synthesized starting from bio-sourced reagents. Itaconic acid, widely recognized as an effective biobased photocurable monomer, and myrcene, a terpene consisting of two isoprene units, are employed in a Diels-Alder cycloaddition to achieve a co-monomer (My-DMI) for the new photocurable polyesters. By exploring various molecular weights, diols and ratios between itaconate and My-DMI, we synthesized eight different polyesters. By combining these with appropriately designed reactive diluents, we successfully tuned the mechanical properties of the 3D printed materials, ranging from very flexible to extremely rigid, depending on the diol chain length and itaconate contents. Additionally, we provide a detailed evaluation of the biobased content of each formulation according to the OK BIOBASED labelling for plastics, finding biobased content as high as 97 % in most cases.

Design, synthesis, and biological evaluation of (E)-3-(3-methoxy-4-substituted phenyl)-acrylic acid derivatives: Role of compound S17 in regulating lipid accumulation via AMPK activation

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a global public health concern characterized by excessive lipid accumulation in the liver. Ferulic acid (FA), a common foodborne phenolic acid, has been shown to reduce lipid accumulation by activating adenosine monophosphate-activated protein kinase (AMPK) and suppressing the expression of sterol regulatory element-binding protein-1 (SREBP-1). In this study, we synthesized a new class of (E)-3-(3-methoxy-4-substituted phenyl)-acrylic acid derivatives as AMPK activators. Among these derivatives, compound S17 demonstrated a more potent inhibitory effect on lipid accumulation compared to its counterparts. Specifically, S17 notably diminished intracellular triglyceride (TG) levels and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are indicators of liver function. In addition, S17 curtailed intracellular lipid accumulation by activating the AMPK signaling pathway and down-regulating the protein expression of SREBP-1 in free fatty acid (FFA)-induced HepG2 cells. Therefore, findings from this study strongly suggest that compound S17 may serve as a promising therapeutic candidate for the treatment of NAFLD.

Cobalt-Catalyzed Enantioselective Hydroboration of α-Substituted Acrylates.

Even though metal-catalyzed enantioselective hydroborations of alkenes have attracted enormous attention, few preparatively useful reactions of α-alkyl acrylic acid derivatives are known, and most use rhodium catalysts. No examples of asymmetric hydroboration of the corresponding α-arylacrylic acid esters are known. In our continuing efforts to search for new applications of earth-abundant cobalt catalysts for broadly applicable organic transformations, we have identified 2-(2-diarylphosphinophenyl)oxazoline ligands and mild reaction conditions for efficient and highly regio- and enantioselective hydroboration of α-alkyl- and α-aryl- acrylates, giving β-borylated propionates. Since the C-B bonds in these compounds can be readily replaced by C-O, C-N, and C-C bonds, these intermediates could serve as valuable chiral synthons, some from feedstock carbon sources, for the synthesis of propionate-bearing motifs including polyketides and related molecules. Two-step syntheses of "Roche" ester from methyl methacrylate (79%; er 99:1), arguably the most widely used chiral fragment in polyketide synthesis, and tropic acid esters (∼80% yield; er ∼93:7), which are potential intermediates for several medicinally important classes of compounds, illustrate the power of the new methods. Mechanistic studies confirm the requirement of a cationic Co(I) species [(L)Co]+as the viable catalyst in these reactions and rule out the possibility of a [L]Co-H-initiated route, which has been well-established in related hydroborations of other classes of alkenes. A mechanism involving an oxidative migration of a boryl group to the β-carbon of an η4-coordinated acrylate-cobalt complex is proposed as a plausible route.

Exploiting 3-Oxidopyraziniums toward Diazabicyclo[3.2.1]octanes and Their Conversion into Diazabicyclo[2.2.2]octanes and Tricyclic Lactone-Lactams.

3-Oxidopyraziniums are azomethine ylides derived from 2(1H)-pyrazinones that can undergo 1,3-dipolar cycloadditions with acrylate and acrylic acid derivatives. The cycloaddition of 1-(4-methoxybenzyl)-5,6-dimethyl-3-oxidopyrazinium with methyl and tert-butyl acrylate and with methyl crotonate afforded a 3,8-diazabicyclo[3.2.1]octane in 51-73% yield together with traces of the 2,5-diazabicyclo[2.2.2]octane. In contrast, cycloaddition of this 3-oxidopyrazinium with methyl 2-phenyl acrylate provided the [2.2.2] product in 40% yield. Herein, we show that the 2,5-diazabicyclo[2.2.2]octanes were formed from the [3.2.1] compounds via a Wagner-Meerwein rearrangement. Remarkably, when acrylic acid and 2-phenylacrylic acid were employed as dipolarophiles, novel tricyclic fused lactone-lactam systems were obtained in 71% and 50% yields, respectively. The formation of these tricyclic compounds can be rationalized via the mechanism described above followed by lactonization of the 2,5-diazabicyclo[2.2.2]octane.

A quadruple-stimuli responsive supramolecular hydrogel constructed from a poly(acrylic acid) derivative and β-cyclodextrin dimer.

The fabrication of stimulus-responsive supramolecular hydrogels as smart materials has attracted much attention in recent years. However, the multi-stimuli responsiveness often requires complicated chemical synthesis and rational molecular design. Herein, a quadruple-stimuli responsive supramolecular hydrogel was designed through the host-guest interaction between a β-CD dimer and a methoxy-azobenzene (mAzo) and ferrocene (Fc) grafted poly(acrylic acid) derivative, as well as through the electrostatic interaction of negatively charged carboxyl side groups. Owing to the dynamic properties of the host-guest and electrostatic interactions, reversible sol-gel transition can be triggered by various stimuli, including temperature, light irradiations, pH changes and chemical redox reagents. As a result, the release of rhodamine B loaded in the hydrogel can be accelerated by green light irradiation, oxidizing agents and low pH, demonstrating potential applications in biomedical materials.

Synthesis and antiproliferative activity of 2-oxo-3-phenylquinoxaline derivatives and related compounds against colon cancer.

We have designed 17 new 2-oxo-3-phenylquinoxalines via the chemoselective Michael reaction of 3-phenylquinoxalin-2(1H)-one with acrylic acid derivatives. The ester, ethyl 3-(2-oxo-3-phenylquinoxalin-1(2H)-yl)propanoate, was reacted with hydroxylamine and hydrazine to produce N-hydroxy-3-(2-oxo-3-phenylquinoxalin-1(2H)-yl)propanamide and hydrazide, respectively. Further modifications were made through reactions with isothiocyanates and azide coupling with amines, yielding thiosemicarbazides and N-alkyl derivatives. Molecular docking studies identified compound 7j as the most potent binder, fitting well into the active site, with the phenyl ring occupying the S1 pocket and the amino acid chain positioned in the S2 pocket. The synthesized compounds (2a, 4, 7a, 7g, 7d, 7h, 7e, 7b, 7c, 7f, and 7j) were evaluated for their anti-cancer activity on colorectal cancer (HCT-116) cells. Compounds 2a and 7j showed significant reductions in cell viability, with IC50 values of 28.85 ± 3.26 μg mL-1 and 26.75 ± 3.50 μg mL-1, respectively. Image analysis of HCT-116 cells treated with 60 μg mL-1 of compound 7j for 48 hours revealed notable morphological changes in both nuclei and cells. The number of cells reduced from 447 in the control to 238 in the treated group, with a corresponding reduction in the area covered by cells from 41.9% to 17.6%. Nuclear disintegration and chromatin fragmentation were observed, confirming apoptosis. These results highlight the potent cytotoxic effect of compound 7j.

Monte Carlo optimization based QSAR modeling of the cytotoxicity of acrylic acid-based dental monomers

Acrylic acid derivatives are extensively utilized as initial monomers in dental materials. Nevertheless, these substances exhibit cytotoxicity towards different cell types, a phenomenon that must be reduced in future materials. The primary objective of this research is to establish a QSAR model for the prediction of cytotoxic effects and to identify molecular fragments and descriptors with mechanistic interpretations that play a role in cytotoxic effects. The Monte Carlo optimization technique was employed QSAR models that are not reliant on conformation. These models utilized both molecular graph-based and SMILESbased descriptors. By employing a variety of statistical methodologies, an assessment of the predictive capabilities and resilience of the established QSAR models was achieved. The demonstrated numerical values used for their validation underscore the strong suitability of these QSAR models. The Monte Carlo optimization technique effectively identified molecular fragments represented in QSAR modeling through the use of SMILES notation, elucidating their impact on cytotoxicity, both positively and negatively. Given that the majority of molecular databases adhere to this molecular structure conformation, the featured QSAR models can serve as a rapid and precise screening tool for novel dental monomers.

Enantioselective hydrogenation of acrylic acids

Enantioselective hydrogenation of acrylic acid derivatives provides a straightforward access to optically active molecules of biological interest such as Naproxen or Ibuprofen as lead molecules. Initially performed with rhodium and ruthenium catalysts, this reaction has successively seen the appearance of efficient iridium catalysts and more recently catalysts based on non-noble metals. A huge variety of chiral ligands has been introduced, leading to productive and selective metal/ligand associations. The present review provides a chronological report of the advances that have been done during the last fifty years for the preparation of optically active acids via enantioselective hydrogenation of prochiral α,β-unsaturated acids.

Low‐Volatile Binder Enables Thermal Shock‐Resistant Thin‐Film Cathodes for Thermal Batteries

Manufacturing thin‐film components is crucial for achieving high‐efficiency and high‐power thermal batteries (TBs). However, developing binders with low‐gas production at the operating temperature range of TBs (400–550 °C) has proven to be a significant challenge. Here, we report the use of acrylic acid derivative terpolymer (LA136D) as a low‐volatile binder for thin‐film cathode fabrication and studied the chain scission and chemical bond‐breaking mechanisms in pyrolysis. It is shown LA136D defers to random‐chain scission and cross‐linking chain scission mechanisms, which gifts it with a low proportion of volatile products (ψ, ψ = 39.2 wt%) at even up to 550 °C, well below those of the conventional PVDF (77.6 wt%) and SBR (99.2 wt%) binders. Surprisingly, LA136D contributes to constructing a thermal shock‐resistant cathode due to the step‐by‐step bond‐breaking process. This is beneficial for the overall performance of TBs. In discharging test, the thin‐film cathodes exhibited a remarkable 440% reduction in polarization and 300% enhancement in the utilization efficiency of cathode materials, while with just a slight increase of 0.05 MPa in gas pressure compared with traditional “thick‐film” cathode. Our work highlights the potential of LA136D as a low‐volatile binder for thin‐film cathodes and shows the feasibility of manufacturing high‐efficiency and high‐power TBs through polymer molecule engineering.

Hybrid Electrically Conductive Hydrogels with Local Nerve Growth Factor Release Facilitate Peripheral Nerve Regeneration.

It is challenging to treat peripheral nerve injury (PNI) clinically. As the gold standard for peripheral nerve repair, autologous nerve grafting remains a critical limitation, including tissue availability, donor-site morbidity, immune rejection, etc. Recently, conductive hydrogels (CHs) have shown potential applications in neural bioengineering due to their good conductivity, biocompatibility, and low immunogenicity. Herein, a hybrid electrically conductive hydrogel composed of acrylic acid derivatives, gelatin, and heparin with sustained nerve growth factor (NGF) release property was developed. The rat sciatic nerve injury (SNI) model (10 mm long segment defect) was used to investigate the efficacy of these hydrogel conduits in facilitating peripheral nerve repair. The results showed that the hydrogel conduits had excellent conductivity, mechanical properties, and biocompatibility. In addition, NGF immobilized in the hydrogel conduits had good sustained release characteristics. Finally, functional recovery and electrophysiological evaluations, together with histological analysis, indicated that the hydrogel conduits immobilizing NGF had superior effects on motor recovery, axon growth, and remyelination, thereby significantly accelerating the repairing of the sciatic nerve. This study demonstrated that hybrid electrically conductive hydrogels with local NGF release could be effectively used for PNI repair.

ANTIMICROBIAL ACTIVITY OF PROTON SALTS OF 3-(SULFAMOYLPHENYLCARBAMOYL)ACRYLIC ACID DERIVATIVES WITH AMINOPYRIDINE DERIVATIVES

Ten proton transfer salts (9-18) were synthesized from the reaction of 2-aminopyridine (1), 2-amino-3/4/5/6-methylpyridines (2-5) and 3-aminomethylpyridine (6) with (E)-3-(3/4-sulfamoylphenylcarbamoyl)acrylic acid (7 and 8), respectively. Bacillus subtilis (wild culture), Candida albicans (ATCC 14053) (yeast), Enterococcus faecalis (ATCC 29212) (Gram positive), Escherichia coli (ATCC 25922), Listeria monocytogenes (ATCC 7644), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (NRRL B-767) (Gram negative) bacterial microorganisms have been tested against the antimicrobial evaluation of compounds (1–18). Vancomycin, Cefepime, Levofloxacin and the antifungal substance Fluconazole were used as antibacterial reference compounds for comparing the MIC values of 1-18. Compounds 1, 3-6, 8-13, 15, 17 and 18 for E. faecalis, 5 for B. subtilis, 1, 3-12, 15, 17 and 18 for S. aureus, 3, 9, 10, 13, 15 and 17 for L. monocytogenes, 16 for E. Coli and 4 for P. aeruginosa the best effect are observed. Proton transfer salts {9, 14, 15 and 17} were showed higher effect than Fluconazole while other compounds (except compounds 2 and 4) had similar effects with Fluconazole. The compounds 2 and 4 showed less activity than Fluconazole.

Antioxidant and Hypolipidemic Activities of Cinnamic Acid Derivatives.

Oxidative stress and hyperlipidemia are important factors for the initiation and progression of various cell degenerative pathological conditions, including cardiovascular and neurological diseases. A series of cinnamic acid-derived acids, such as ferulic acid, sinapic acid, 3,4-dimethoxycinnamic acid, p-coumaric acid, and (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid, were esterified or amidated with various moieties, bearing different biological activities, and evaluated. The antioxidant and radical scavenging abilities of the compounds via inhibition of rat hepatic microsomal membrane lipid peroxidation, as well as their interaction with the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), were assessed. Further, their hypolipidemic activity in vivo was tested. The majority of the obtained compounds demonstrated considerable radical scavenging and antioxidant action, with a parallel decrease in Triton-induced hyperlipidemia in rats. The (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid derivative with morpholine and 4-methylpiperidine (compounds 4 and 13, respectively) significantly decreased triglycerides and total cholesterol in the plasma of hyperlipidemic rats, with an antioxidant capacity similar to that of the antioxidant Trolox. The compounds were designed to exhibit antioxidant and hypolipidemic pharmacological actions, and this succeeded for the majority of them. Thus, such agents may be of interest in conditions and diseases implicating oxidative stress and dyslipidemia.

STUDY OF THE COMPOSITION OF AUXILARY SUBSTANCES WHICH ARE BEEN RESPONSIBLE FOR CONDUCT OF PROLONGED (MODIFIED) ACTION OF MEDICINES

Abstract. 
 Introduction. Realization of action of medicines, including prolonged and modified, depends on composition of auxiliary substances in a medicinal form.
 Aim. Study of the composition of auxilary substances which are been responsible for conduct of prolonged (modified) action of medicines.
 Methods. Content analysis, system analysis, documental analysis.
 Results. Hydrophilic and inert components are prevailing among auxiliary substances of prolonged (modified) solid oral medicinal products (SOMP) presented in the State Register of Ukraine. Hydrophobic substances and substances, soluble at the defined values of рН, are being in less. Auxiliary substances of prolonged (modified) SOMP are presented by the derivatives of Cellulose, Ethyleneglycol, Acrylic acid, Pyrrolidone, Alginic acid, inorganics and wax-like components. Gummi and hydrocarbons are also being in the composition of prolonged SOMP.
 Conclusion. The nomenclature of auxiliary substances that are in the composition of prolonged (modified) SOMP has differences. Certain ratios of auxiliary components in the composition of SOMP are providing adjusting of time of release of medicinal substance from medicinal form.

DFT and In-silico Investigations, along with In-vitro Antitumor and Antimicrobial Assessments of Pharmacological Molecules.

Molecules bearing an active methylene bridge are one of the most fruitful and remarkable precursors that have been incorporated into the synthetic strategy of an assortment of bioactive compounds. The reactive methylene derivatives have been endowed with multiple reactions, which target biological and medicinal applications and result from their structural diversity and discrete reactivity. The present report endeavors to synthesize, characterize, and in-vitro evaluate several novel propanoic acids, coumarin, and pyrazole derivatives as antimicrobial and antiproliferative agents. The in-silico molecular docking, physicochemical, pharmacokinetic/ADMET, bioactivity, and drug-likeness predictions were conducted for all the synthesized compounds. The highest docking score is -9.9 and -8.3 kcal/mol, respectively, for compound 9 (azocoumarin) and 13 (acrylic acid derivative) with the target proteins E. coli topoisomerase II, DNA gyrase subunit B and PI3K p110α domain, respectively. Moreover, this study predicts the synthesized molecules that may inhibit the novel COVID-19, obtained through virtual screenings only, where compounds 9, 13, 14, 17, and 19 came to the limelight with good docking scores i.e., more than -8 Kcal/mol. Safety profiling of the most potent compound 9 was utilized against normal cell lines and the hemolytic effect on RBCs. The in-silico ADMET studies of the synthesized compounds revealed moderate to good -likeness, high gastro intestinal (GI) absorption, and inhibiting the Cytochrome CYP2C19 and CYP2C9 and all the derivatives possess non-cancerous nature. The in-vitro screening demonstrated that several of the novel molecules are promising drug candidates. The density functional theory (DFT) theoretical calculations were performed to calculate the energy levels of the FMOs and their energy gaps, dipolemoment, andmolecular electrostatic potential. Such parameters, along with the physicochemical parameters, could be a good tool to confirm biological activity.

Synthesis of New Dehydrodieugenol Derivatives via Olefin Cross Metathesis and In Vitro Evaluation of Their Trypanocidal Activity

Ruthenium-catalyzed cross metathesis using biseugenol (1) with electron-deficient olefins methyl (2a) and ethyl (2b) acrylates, acrylic acid (2c), acrylonitrile (2d), and methyl methacrylate (2e) derivatives have been conducted to afford respective derivatives 3a–3e with good yields and excellent conversion rates. Activity of prepared compounds against trypomastigote and amastigote forms of Trypanosoma cruzi and mammalian cytotoxicity have been evaluated. The results obtained indicate that the IC50 values for amastigotes of compounds 3b and 3d are quite similar to those of biseugenol (1), but unlike this compound, they show reduced toxicities with SI values similar to those of the standard drug benznidazol.

CORRELATION OF THE COMPONENT COMPOSITION OF HUMIC ACIDS OF PELOIDS WITH THEIR POLYMODAL ACTION

Relevance. The source of humic substances and the method of isolation determines their structure, the specificity of binding of individual fragments, the degree of condensation and conjugation, molecular weights and other characteristics. Humic acids of peloids have a high pharmacological activity due to the presence of various functionals in their composition, which, along with a high molecular weight, allows them to be attributed to the group of polyelectrolytes and determines the universality of the effect. The aim of the work was to identify the components of humic acid hydrolysate of low-mineralized silt sulfide mud to substantiate their polymodal action. Material and methods. The object of the study was a solution obtained by extraction into hexane, products of acid hydrolysis of humic acids. The obtained samples were studied using the following methods: chromatography-mass spectrometry (GC-MS) on an Agilent 7890 A chromatograph, IR spectroscopy on a Perkin-Elmer System - 2000 spectrophotometer, elemental quantitative analysis on a Vario EL analyzer. Results. GC-MS analysis of humic acid hydrolysis products showed the presence of acidic components in the sample and includes both low- and high-molecular fatty monobasic and dibasic acids of saturated unsaturated type. The presence of phenolic derivatives of acrylic acid in the composition causes the inhibitory effect of HA on cell proliferation. The neutral fraction is represented by high-molecular alcohols of natural origin. Conclusion. Thus, the above components of the hydrolysate justify the currently established and potentially possible effects of humic acids of peloids.

Infrared Spectroscopy of Polymers X: Polyacrylates

Acrylate polymers are derivatives of acrylic acid, but contain a plethora of different functional groups and are best discussed by themselves. In this column, we study the spectrum of an important polymer, polymethyl methacrylate (PMMA), which is otherwise known as plexiglass, and is found in windows, car parts, and paint. We then study the spectra of PMMA mixtures and copolymers in detail.

Design, synthesis and antiproliferative screening of newly synthesized acrylate derivatives as potential anticancer agents.

A new series of acrylic acid and acrylate ester derivatives as modified analogs of tubulin polymerization inhibitors were designed and synthesized. The antiproliferative activity of the constructed molecules was investigated against MCF-7 breast carcinoma cells using CA-4 as positive molecule. Methyl acrylate ester 6e emerged as the most potent cytotoxic agent against MCF-7 cells, with an IC50 value of 2.57 ± 0.16 μM. Also, methyl acrylate ester molecule 6e showed good β-tubulin polymerization inhibition activity. Cellular cycle analysis showed that compound 6e can arrest MCF-7 cells at the G2/M phase. In addition, this compound produced a significant increase in apoptotic power as compared to control untreated MCF-7 cells. Furthermore, the effect of acrylate ester 6e on the gene expression levels of p53, Bax and Bcl-2 was investigated. This molecule increased the expression levels of both p53 and Bax, and decreased the gene expression level of Bcl-2 as compared to control untreated MCF-7 carcinoma cells.

Development of an α'-hydroxy enone for the aminocatalytic asymmetric formal conjugate addition of aldehydes to acrylates, vinyl ketones and acrolein.

Aminocatalytic asymmetric conjugate addition of aldehydes to Michael acceptors is a well established C-C bond forming methodology. However, various acrylic-type acceptors, including acrylic acid derivatives and acrolein, remain reluctant. Here we demonstrate that the internal H-bonding self-activation in α'-hydroxy enones allows them to react smoothly with enolizable aldehydes using commercially available aminocatalysts to afford adducts in good yields and high enantioselectivity. Straightforward conversion of the ketol moiety of these adducts into aldehyde, ketone and carboxylic acid functionalities offers an indirect, unified entry to products derived from acrolein, alkyl-vinyl ketones and acrylates, respectively.