Capsaicin Derivatives Research Articles

Design, Synthesis and Biological Evaluation of Novel Capsaicin Analogues Containing Heterocyclic Fatty Acids

AbstractThere is an urgent need to study safe and biocompatible medicinal compounds which necessitates the discovery of new agents from simple natural starting materials. In this study, eight novel capsaicin derivatives have been synthesized by combination of oxadiazole containing fatty acids with vanillyl amide. All the compounds were characterized by spectral analysis and were examined for their cytotoxicity, antimicrobial, antioxidant and anti‐inflammatory properties. The antioxidant activity of the synthesized derivatives was evaluated by 1,1‐diphenyl‐2‐picryl‐hydrazyl (DPPH) and thiobarbituric acid reactive substances (TBARS) assays. All of the synthesized derivatives have exhibited significant antioxidant activity in comparison to butylated hydroxy toluene (BHT) which is used as a reference antioxidant. The novel capsaicin derivatives with nitro (8 e) and methoxy substituents (8 f, 8 g and 8 h) exhibited the most significant antioxidant activity compared with BHT. In cytotoxicity assay against three cell lines, the derivative with bromo substituent showed excellent activity against B16‐melanoma cancer cell line followed by nitro and methoxy analogs which showed promising activity against HepG2‐ hepato and DU145‐prostate cancer cell lines respectively. In addition, all the derivatives exhibited moderate broad spectrum antibacterial, antifungal and anti‐inflammatory activity.

Synthesis and Antibacterial Activity of Capsaicin Derivatives Containing Phenolic Hydroxyl Groups

AbstractBacterial infections tend to cause a series of cytopathic reactions and have become a major threat to human life. Among them, phenolic compounds are widely used as a natural antibacterial derivative for antifouling and antibacterial applications. In this study, four phenolic hydroxyacrylamide monomers have been successfully prepared using capsaicinoid derivatives as inspiration (named as OHABA, PHABA, AHMA, and AMTHBA, respectively) and the chemical structures were confirmed by FT‐IR, 1H‐NMR, 13C‐NMR. The minimum inhibitory concentration (MIC) assay and plate antibacterial assay were measured to explore the antibacterial properties of the monomer. The results showed that four capsaicin derivatives exhibited antibacterial activity, and the antibacterial properties of the four monomers from strong to weak were PHABA, OHABA, AHMA and AMTHBA. The best antibacterial activity was PHABA (MIC for E. coli: 1.6 mg/mL, bacteriostasis rate: 82.46 %, MIC for S. aureus: 1.6 mg/mL, bacteriostasis rate: 69.58 %). Both the cluster effect of monomers and the spatial distribution of phenolic hydroxyl groups in the structure of derivatives affect the antibacterial properties.

Capsaicin mimic-based antifouling and antibacterial polyester nanofiltration membranes with tunable crosslinked structures

Polyester thin-film composite (PE TFC) nanofiltration membranes based on the interfacial polymerization (IP) of polyols/polyphenols and acyl chloride continue to attract considerable attention for textile wastewater treatment due to their excellent antifouling properties. Herein, N-(5-methyl acrylamide-2,3,4 hydroxy benzyl) acrylamide (AMTHBA), a polyphenol-inspired capsaicin derivative, was first utilized as an aqueous monomer for the preparation of antifouling and antibacterial PE TFC membranes via the IP process. The moderate reactivity of AMTHBA and its unique solubility enabled a rational control of the crosslinking density of PE membranes, allowing the formation of structures from loose to dense through an adjustment of the AMTHBA concentration. The densely crosslinked AM-TMC PE membrane exhibited favorable desalination performance, with a water permeance of 21.8 L m−2 h−1 bar−1 and a Na2SO4 rejection of 83.8 %. The loosely crosslinked AM-TMC PE membrane exhibited excellent dye/salt separation performance, with high dye rejections (e.g., 98.5 % for MB) and low salt rejections (e.g., 4.0 % for NaCl), as well as high water permeance (30.4 L m−2 h−1 bar−1). In contrast, the capsaicin-containing PE TFC membranes also demonstrated markedly enhanced resistance to bacterial growth and organic fouling. These findings indicate that AM-TMC PE membranes present novel avenues for the advancement of task-specific separation membranes.

A green, facile, and practical preparation of capsaicin derivatives with thiourea structure

Capsaicin derivatives with thiourea structure (CDTS) is highly noteworthy owing to its higher analgesic potency in rodent models and higher agonism in vitro. However, the direct synthesis of CDTS remains t one or more shortcomings. In this study, we present reported a green, facile, and practical synthetic method of capsaicin derivatives with thiourea structure is developed by using an automated synthetic system, leading to a series of capsaicin derivatives with various electronic properties and functionalities in good to excellent yields.

Novel post-functionalized polymer microspheres containing capsaicin as reversed-phase chromatography stationary phase separation for hydrophilic compounds

Here, we created for the first time that highly stable polymer microspheres copolymerized with capsaicin derivative, divinyl benzene, and N-(Hydroxymethyl)acrylamide could be efficient for reversed-phase high-performance liquid chromatography (RP-HPLC) by using a simple “one-pot cooking” method, which had the potential to be produced in large quantities. Then, the spheres were post-functionalized with two different monomers, N-vinyl formamide and 4-acrylomorpholine by double coating, which had ideal mechanical strength and efficiency as stationary phase. In order to reach best separation condition, the effects of buffer concentration, pH, column temperature, and mobile phase polarity on the retention rate were studied. Specifically, the interaction mechanism showed that the stationary phase had hydrophobic and electrostatic interaction with the water-soluble vitamins. It is of significant interest that all columns had excellent precision and accuracy (RSD < 4 %). Taken together, this study played a specific role in promoting the development of a new reverse-phase mode for separating hydrophilic compounds.

Capsaicin derivatives: Synthesis and biological activity

AbstractCapsaicin is the main active ingredient of chili peppers and the most pungent alkaloid. It is reported that capsaicin has many pharmacological effects such as analgesia, anticancer, anti‐inflammatory, antibacterial, and anti‐obesity. However, the application of capsaicin is limited by its adverse side effects, such as stomach irritation, stomach cramps, and burning sensation. In recent years, many capsaicin derivatives have been synthesized and their biological activities have been evaluated. Some capsaicin derivatives have shown promising activities in cells and animal models. Herein, we described the synthesis and biological activity of capsaicin and its derivatives. It is hoped that the insights obtained in this perspective will facilitate the synthesis of a second generation of capsaicin analogs with improved biological activities.

Enhancing biofouling resistance in microfiltration membranes through capsaicin-derivative functionalization.

The primary focal point in the fabrication of microfiltration membranes revolves around mitigating issues of low permeability stemming from the initial design as well as countering biofouling tendencies. This work aimed to address these issues by synthesizing an antibacterial capsaicin derivative (CD), which was then grafted to the poly(vinylidene fluoride-co-chlorotrifluoroethylene)-g-polymethacrylic acid (P(VDF-CTFE)-g-PMAA) matrix polymer, resulting in an antibacterial polymer (PD). Notably, both CD and PD demonstrated low cytotoxicities. Utilizing PD, a microfiltration membrane (MA) was successfully prepared through non-solvent-induced phase inversion. The pore sizes of the MA membrane were mainly concentrated at around 436 nm, while the pure water flux of MA reached an impressive value of 62 ± 0.17 Lm-2 h-1 at 0.01 MPa. MA exhibited remarkable efficacy in eradicating both Gram-negative (E. coli) and Gram-positive bacteria (Bacillus subtilis) from its surface. Compared with M1 prepared from P(VDF-CTFE), MA exhibited a lower flux decay rate (41.00% vs. 76.03%) and a higher flux recovery rate (84.95% vs. 46.54%) after three cycles. Overall, this research represents a significant step towards the development of a microfiltration membrane with inherent stable anti-biofouling capability to enhance filtration.

Synthesis and evaluation of the biological properties of boron-containing and boron-omitted capsaicin derivatives on human cancer cell lines

Boron-containing and boron-omited derivatives based on the structural motif of capsaicin have been synthesized. The vanillyl amide moiety of the parent capsaicin molecule was retained and the boron atom was incorporated into the aliphatic region. All new compounds have been fully characterized using various analytical techniques including multinuclear NMR spectroscopy and elemental analysis. Thereafter, their antiproliferative activity was evaluated on 3 cancer cell lines (HT-29, M21 and MCF7) leading to the selection of compounds 4c and 7c for assessment of their antitumoral activities on HT-29 tumors grafted onto the chorioallantoic membrane of developing chick embryos. The boro-capsaicinoid 4c exhibits good antitumoral activity with a 55% decrease in tumor mass.

Preparation of acrylic metal salt resin containing capsaicin derivative structure and study of anti-fouling properties

Modifications of acrylic resins with environmentally friendly compounds often solve the problems of marine fouling. In this work, capsaicin derivatives-modified acrylic acid resins were successfully synthesized via free radical polymerization and condensation reactions of monomeric acrylic acid, capsaicin derivatives, metal salts and benzoic acid and structurally characterized by infrared spectroscopy and nuclear magnetism. The physicochemical properties of the synthesized resin coatings were tested with a rotary viscometer, gel permeation chromatography, video optical contact angle measurements and a laser confocal tester. The self-polishing and antifouling properties of the resins were investigated with dynamic simulation experiments, algae inhibitions, bacterial inhibition experiments and real sea antifouling experiments. By comparing with the acrylic resin without capsaicin derivatives, the acrylic resin with added capsaicin derivatives had good antifouling performance, and the optimal content was 2.5 %. In summary, the capsaicin derivative-modified acrylic metal salt resins have good self-polishing properties and antifouling properties.

A highly antifouling and eco-friendly hydrogel coating based on capsaicin derivative -functionalized polymer

Antifouling hydrogels have received extensive attention in the field of marine antifouling due to their excellent hydrophilicity and environmental friendliness. However, the antifouling applications of traditional hydrogels are limited by their poor antibacterial properties, and capsaicin derivatives, as nontoxic and environmentally friendly antifoulants, can be used to improve the antibacterial properties of hydrogels. From the perspective of practical application, hydrogels were obtained by crosslinking the copolymer of the capsaicin derivative N,N'-((4,5,6-trihydroxy-1,3-phenylene) bis (methylene)) diacrylamide (TPA), lipophilic monomers and hydrophilic monomers. This hydrogel exhibited anti-protein performance due to its hydrophilicity, and the capsaicin derivative caused the hydrogel coating to exhibit excellent algae inhibition performance (the minimum adhesion density of diatoms on the surface of the hydrogel coating was less than 440 cells/mm2), better algae anti-adhesion abilities than hydrogel reported in the other paper, and antibacterial effects (the antibacterial rate was more than 95%). After 73 d of panel testing in a real marine environment, there was still a good antifouling effect in the hydrogel coating. Hence, the antifouling performance was improved significantly by capsaicin derivative (TPA)-functionalized hydrogel coating. A new strategy is provided in this study for the preparation of hydrogels with superior marine antifouling properties.

Antifouling improvement in Pb2+ ion selective electrodes by using an environmentally friendly capsaicin derivative

Biofouling is a critical issue for ion selective electrodes (ISE) in complex aqueous systems, seriously compromising the analytical performance of the electrodes (i.e., stability, sensitivity, and lifetime). Herein, an antifouling solid lead ion selective electrode (GC/PANI-PFOA/Pb2+-PISM) was successfully prepared by adding propyl 2-(acrylamidomethyl)-3,4,5-trihydroxy benzoate (PAMTB), an environmentally friendly capsaicin derivative, into the ion-selective membrane (ISM). The presence of PAMTB caused no loss in the detection performance of GC/PANI-PFOA/Pb2+-PISM (e.g., detection limit (1.9×10-7M), response slope (28.5±0.8mV/decade), the response time (20s), stability (8.6±2.9 μV/s), selectivity and no water layer), whilst imparting an excellent antifouling effect with an antibacterial rate of 98.1% when the content of PAMTB in the ISM was 2.5wt%. Further, GC/PANI-PFOA/Pb2+-PISM maintained stable antifouling properties, excellent potential response, and stability even after soaking in a high-concentration bacterial suspension for 7 days.

Synthesis of Hydrophobically Associating Polymers with Natural Product Structures by a One‐Pot Method – Comparison of Ethanol Treatment and Freeze‐Drying

AbstractPolyacrylamide‐based hydrophobically associating polymers (HAPAM) containing capsaicin derivatives and itaconic acid with acrylamide (AM) and methacrylic acid (MAA) as the main bodies, and N‐vinylpyrrolidone (NVP) as the functional monomer are prepared by a one‐pot synthesis of the soap‐free emulsion polymerization process. The structure is characterized by fourier transform infrared (FTIR) and 1H nuclear magnetic resonance (1H NMR), and thermal gravimetric analyzer (TGA) explores thermal stability. For achieving proper purification, excellent preservation and convenient transportation of the polymer and to advance its practical engineering applications, two different treatments, namely ethanol washout and freeze‐drying, are carried out and compared. The surface morphology observation manifests that the freeze‐drying products (DHPAM) better protect the three‐dimensional cross‐linked network structure formed by various supramolecular forces such as hydrophobic association, electrostatic and hydrogen bonding inside the polymer than the ethanol washout products (EHPAM), which well explains why DHPAM has lower critical association concentration (CAC), greater resistance to high temperature and high salt, and better corrosion inhibition performance than EHPAM. It is significant for strengthening the application of polymers in related fields, especially oil and gas extraction.

Preparation of highly permeable and selective nanofiltration membranes with antifouling properties by introducing the capsaicin derivative into polyamide thin selective layer by bidirectional interfacial polymerization

A novel thin film composite (TFC) nanofiltration (NF) membrane was prepared by introducing the capsaicin derivative AMTHBA into polyamide (PA) layer by bidirectional interfacial polymerization. Ultrathin, smooth and defect-free PA layers can be prepared by bidirectional interface polymerization. Meanwhile, the surface properties of NF membranes were precisely regulated by adjusting the concentration of AMTHBA in an aqueous solution. As a result, the AMTHBA-PAR/PAF/PS membrane displayed superior permeance owing to its hydrophilic and negatively charged surface. The optimized NF membrane exhibited an ultrahigh permeance of 128.95 L m−2 h−1 (almost two-fold higher permeance than that of the nanofiltration membrane prepared by traditional interfacial polymerization), together with a steady efficiency above 98.43% for rejection of Na2SO4. In addition, the AMTHBA-PAR/PAF/PS membrane exhibited excellent antifouling performance and therefore has broad application prospects in the field of water treatment.

Experimental and theoretical investigations on the inhibition of mild steel corrosion by capsaicin derivatives in hydrochloric acid

The protective properties of two capsaicin derivatives named N,N'-((4‑hydroxy-2,5,6-trimethyl-1,3-phenylene)bis(methylene))diacrylamide and N,N'-((5‑chloro-2,4-dihydroxy-1,3-phenylene)bis(methylene))diacrylamide in hydrochloric acid for mild steel were investigated. Electrochemical experiments showed that the inhibition efficiency of the two capsaicin derivatives as mixed inhibitors reached 96.24% and 93.71% at 0.3 g/L, respectively. Surface observations show that the capsaicin derivatives adhere firmly to the mild steel by forming a barrier. These two inhibitors fit the Langmuir adsorption isotherm and mixed adsorption type. The computational studies (DFT and MD) provide excellent support for the experimental results of both inhibitors.

Membrane-Active Nonivamide Derivatives as Effective Broad-Spectrum Antimicrobials: Rational Design, Synthesis, and Biological Evaluation.

Antibiotic resistance is emerging as a "global public health concern". To address the growing epidemic of multidrug-resistant pathogens, the development of novel antimicrobials is urgently needed. In this study, by biomimicking cationic antibacterial peptides, we designed and synthesized a series of new membrane-active nonivamide and capsaicin derivatives as peptidomimetic antimicrobials. Through modulating charge/hydrophobicity balance and rationalizing structure-activity relationships of these peptidomimetics, compound 51 was identified as the lead compound. Compound 51 exhibited potent antibacterial activity against both Gram-positive bacteria (MICs = 0.39-0.78 μg/mL) and Gram-negative bacteria (MICs = 1.56-6.25 μg/mL), with low hemolytic activity and low cytotoxicity. Compound 51 displayed a faster bactericidal action through a membrane-disruptive mechanism and avoided bacterial resistance development. Furthermore, compound 51 significantly reduced the microbial burden in a murine model of keratitis infected by Staphylococcus aureus or Pseudomonas aeruginosa. Hence, this design strategy can provide a promising and effective solution to overcome antibiotic resistance.

1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549).

A series of novel 1,2,3-triazole derivatives of capsaicin and its structural isomer (new natural product hybrid capsaicinoid) were synthesized by exploiting one-/two-point modification of capsaicin without altering the amide linkage (neck). The newly synthesized compounds were screened for their antiproliferative activity against an NCI panel of 60 cancer cell lines at a single dose of 10 μM. Most of the compounds have demonstrated reduced growth between 55 and 95%, whereas capsaicin (10) has shown reduced growth between 0 and 24%. Compounds showing more than 50% growth inhibition were further evaluated for the IC50 value. Among the cell lines tested, lung cancer cell lines (A549, NCI-H460) were found to be more susceptible toward most of the synthesized compounds. Compounds 14g and 14j demonstrated good antiproliferative activity in NCI-H460 with IC50 values of 6.65 and 5.55 μM, respectively, while compounds 18b, 18c, 18f, and 18m demonstrated potential antiproliferative activity in A549 cell lines with IC50 values ranging between 2.9 and 10.5 μM. Among the compounds, compound 18f was found to demonstrate the best activity with an IC50 value of 2.91 μM against A549. Furthermore, 18f induces cell cycle arrest at the S-phase and disrupts the mitochondrial membrane potential, reducing cell migration potential by inducing cellular apoptosis and higher ROS generation along with a decrease in mitochondrial membrane potential in addition to surface and nuclear morphological alterations such as a reduction in the number and shrinkage of cells coupled with nuclear blabbing indicating the sign of apoptosis of A549 non-small cell lung cancer cell lines. Compound 18f has emerged as a lead molecule and may serve as a template for further discovery of capsaicinoid scaffolds.

Synthesis and fouling resistance of capsaicin derivatives containing amide groups

Natural capsaicin extracted from pungent plants can impede marine organisms and achieve antifouling effects, and it will not kill marine fouling organisms. Its derivatives inherit the good antifouling effects and toxicity. When it is introduced into an antifouling system, capsaicin can meet the environmental requirements of antifouling coatings. Using N-hydroxymethyl phthalimide and aromatic compounds as raw materials, six new active structural derivatives containing capsaicin were synthesized by the Friedel craft alkylation reaction, and their structures were determined by IR, NMR and MS. The antibacterial and algal inhibitory properties of the compound were tested, and the results revealed it had certain inhibitory effects on Marine bacteria and algae, with strong antibacterial and algal inhibitory properties observed of products D, E and F. The minimum inhibitory concentration was 0.1875 mg/mL, and the highest antibacterial rate of 3 mg/mL was 93.05%. The highest algae inhibition rate on the seventh day was 88.34%, the toxicity was low, and the toxicity grade was low. The compound as an antifouling agent added to marine antifouling coatings shows a good antifouling effect, thus laying a good foundation for research on environmentally friendly antifouling coatings.

Synthesis, Antibacterial and Insecticidal Activities of Novel Capsaicin Derivatives Containing a Sulfonic Acid Esters Moiety.

In order to develop an efficient and broad-spectrum bactericide, a series of novel capsaicin derivatives containing a sulfonic acid esters moiety was synthesized. The structure of these compounds were confirmed by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrum (HRMS). The results of the bioactivities revealed that some target compounds exhibited remarkable antibacterial activity. Compound 3b exhibited the highest activities against Pseudomonas syringae pv. actinidiae (Psa), Xanthomonas oryzae pv. oryzae (Xoo), and Xanthomonas axonopodis pv. citri (Xac), and the values were 86, 54, and 92% at 50 μg/ml, respectively, which were higher than were for thiodiazole copper (87, 34, and 77%) and bismerthiazol (87, 37 and 75%). Although some compounds also showed certain activity against Spodoptera frugiperda, it was weaker than the positive controls monosultap and mulfoxaflor. Thus, the bioassay results recommend that these newly designed and synthesized scaffolds should be used as a bactericide lead compound rather than an insecticide lead compound.

Dependable Performance of Thin Film Composite Nanofiltration Membrane Tailored by Capsaicin-Derived Self-Polymer.

To address trade-off and membrane-fouling challenges during the development of nanofiltration membranes, a thin-film composite membrane was prepared on the basis of interfacial polymerization regulated by adjusting the capsaicin-derived self-polymer poly N-(2-hydroxy-5-(methylthio) benzyl) acrylamide (PHMTBA) on the polysulfone substrate in this study. Through the self-polymerization of the monomer HMTBA with varied contents, microwave-assisted technology was employed to develop a variety of PHMTBAs. It was discovered that PHMTBA is involved in the interfacial polymerization process. Piperazine and PHMTBA competed for the reaction with trimesoyl chloride, resulting in a flatter and looser membrane surface. The PHMTBA-modified membrane presented a typical double-layer structure: a thicker support layer and a thinner active layer. The addition of PHMTBA to membranes improved their hydrophilicity and negative charge density. As a result, the PHMTBA-modified membrane showed dependable separation performance (water flux of 159.5 L m−2 h−1 and rejection of 99.02% for Na2SO4) as well as enhanced anti-fouling properties (flux recovery ratio of more than 100% with bovine serum albumin-fouling and antibacterial efficiency of 93.7% against Escherichia coli). The performance of the prepared membranes was superior to that of most other modified TFC NF membranes previously reported in the literature. This work presents the application potential of capsaicin derivatives in water treatment and desalination processes.

Capsaicin derivatives as antifouling adjuvants

Capsaicin derivatives as antifouling adjuvants