Salicylic Acid Derivatives Research Articles

P098 Worsening Colitis and Congestive Heart Failure Related to Mesalamine Use

BACKGROUND: Five-amino salicylic acid derivatives are generally well-tolerated agents commonly used to treat ulcerative colitis. Serious reactions are rare. We present a case of paradoxical worsening of ulcerative colitis and acute heart failure in a young woman on mesalamine therapy. CASE: A 37-year old white female with a history of sleeve gastrectomy and recently diagnosed mild to moderate extensive ulcerative colitis (UC) had been on oral mesalamine for 1 month. She endorsed worsening symptoms, with 10-12 watery bowel movements daily along with 3-4 episodes of hematochezia and generalized abdominal cramps. Lack of response to prednisone prompted admission. She was found to be severely dehydrated, hyponatremic with a sodium of 132 mEq/L, and anemic with a hemoglobin of 10.2 g/dL (from normal three months earlier). Albumin was decreased at 3.1 g/dL and C-reactive protein (CRP) was elevated at 4.2 mg/dL. Stool tests for Clostridioides difficile, other bacteria, and viruses, were negative. Flexible sigmoidoscopy showed Mayo 3 colitis despite 3 days of IV methylprednisolone. Her hospital course was complicated by acute heart failure presenting as leg edema and shortness of breath. Brain natruretic peptide level was elevated at 550 pg/mL. Echocardiogram revealed global hypokinesis of the left ventricle and an estimated ejection fraction of 30-35%. Given this contraindication to anti-tumor necrosis factor agents, she was started on tofacitinib 10 mg thrice daily. Surgical consultation was also obtained. After three doses her abdominal pain improved, diarrhea decreased to 5 bowel movements daily, and CRP decreased to 1.9 mg/dL. After three days, the dose was decreased to 10 mg twice daily. On clinic follow-up 3 weeks later, she was pain-free and bowel movements were back to baseline with no blood and no diarrhea. CRP and albumin normalized. Her shortness of breath and leg edema had also resolved. Multigated acquisition scan 3 months after discharge showed resolution of left ventricle wall motion abnormalities, and a normal ejection fraction of 61%. DISCUSSION: Five-amino salicylic acids (5-ASA) are relatively safe medications. Serious reactions including pancreatitis, interstitial nephritis, blood dyscrasias, pneumonitis, and Stevens Johnson syndrome, are rare. Infrequently, paradoxical worsening of colitis is seen. This phenomenon is not well understood and there is no consistency in the presence of inflammatory markers. Confirmation requires a mesalamine challenge, which is not often feasible. Acute cardiac side effects from mesalamine are extremely uncommon, potentially serious, and appear dose-independent. The exact mechanism by which it might induce myocardial inflammation and heart failure is unclear. Existing hypotheses include: a hypersensitivity reaction due to inhibition of COX enzyme and subsequent acceleration in metabolism of arachidonic acid to lipoxygenases, humoral-mediated hypersensitivity wherein antibodies against mesalamine cross-react with the myocardium, cell-mediated hypersensitivity, and immunoglobulin E-mediated allergic reaction. Symptoms usually manifest within 2-4 weeks of starting the drug. CONCLUSION: The temporal relationship between our patient’s symptom onset and initiation of mesalamine indicates a causal relationship. Mesalamine should remain on the differential of worsening UC, and acute heart failure, after evaluating for more common causes.

Синтез и биологическая активность ряда эфиров салициловой кислоты

Salicylic acid is currently of little use, but its derivatives are one of the most large-tonnage drugs in the world. However, the natural sources of salicylic acid cannot satisfy the needs for its preparations and therefore the acid and its derivatives are obtained exclusively by synthetic means. Derivatives of salicylic acid are of great interest, due to their high reactivity and widespread use in medical practice as anti-inflammatory, antipyretic, analgesic, antimicrobial, antiseptic and anti-tuberculosis drugs. Currently, there is a fairly large body of data on the synthesis, structure, and biological properties of various derivatives of salicylic acid, however, it should be noted that derivatives of salicylic acid and various derivatives of amino acids and salicylic acid are poorly studied. The relevance of studying the properties of new transformed derivatives of salicylic acid is due to broad prospects that open the borders for realizing the potential for further chemical modification inherent in the structure of these new substances with a combination of several active groups: carbonyl and hydroxyl. Such a combination in a molecule of derivatives based on salicylic acid, containing known pharmacological groups in its structure, often leads to the appearance of a new high hemostatic activity. In the course of our work, we synthesized some esters based on salicylic acid, and also determined the antiplatelet and anticoagulant activity of the first synthesized substances. The study was conducted on the indicators of coagulogram in vitro on human donated blood. It was found that all provided compounds exhibit anti-aggregation activity, some of the compounds obtained by us exhibit anti-aggregation activity of more than 10%. All the experimental work was performed by us at the Department of Anesthesiology and Intensive Care with the course of the Institute of Continuing and Professional Education of the Bashkir State Medical University of the Ministry of Health of Russia on the basis of the Central Research Laboratory of the Bashkir State Medical University of the Ministry of Health of Russia and GBUZ RKB named after G.G. Kuvatova in accordance with the recommendations of the "Guidelines for the preclinical study of new pharmacological substances."

Systematic evaluation of sample preparation for fractionation of phytohormone salicylic acid in fresh leaves

The determination of salicylic acid (SA), an important phytohormone responsible for stress signaling in plants, is of great importance in agricultural studies. However, a critical evaluation of the procedures for the extraction of the analytes and hydrolysis of the conjugated forms of SA is lacking in the literature and the available alternatives are complex, time-consuming, and laborious. In this study, the sample preparation methods for SA fractionation were critically evaluated to develop a simpler and faster alternative procedure. Microwave-assisted extractions were carried out with 2.0 g of fresh leaves and 8.0 mL of a 75% v/v ethanol:water solution at 40 °C for 10 min, followed by alkaline hydrolysis using 100 μL of 0.1 mol L−1 NaOH at 80 °C for 60 min. Free and total SA were determined in crude and hydrolyzed extracts, respectively, by fluorimetry after chromatographic separation of the sample matrix under isocratic elution (25% v/v acetonitrile/phosphate buffer) using a C18 column. Recovery experiments using methyl salicylate and acetylsalicylic acid model compounds demonstrated that the soft microwave-assisted extraction did not decompose the SA derivatives and that alkaline hydrolysis was quantitative. The proposed procedure was successfully applied for fractionation of SA in sugarcane, corn, and soybean leaves with extraction and hydrolysis yields up to 70 and 20% higher than those achieved in previously proposed approaches, respectively. The developed procedure is a simple, fast, and reliable alternative for SA fractionation in crude extracts without sample clean-up, and utilizes dilute reagents and green solvents.

CHARACTERIZATION OF PHARMACOKINETICS OF 2-((3-(CHLOROMETHYL)BENZOYL)OXY) BENZOIC ACID IN RATS BY USING HPLC-DAD METHOD

Objective: A new compound of salicylic acid derivative, namely 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3CBB), was synthesized to find a compound exhibiting higher analgesic activity and smaller ulcer irritation than acetylsalicylic acid (ASA). Therefore, this study aimed to investigate the pharmacokinetics of this new compound in rats, following a single dose oral administration of 3CBB (45 mg/kg BW).
 Methods: Plasma samples of 9 healthy rats were collected before and up to 3 h after its oral administration, following an 18 h fasting period. Plasma concentrations of 3CBB were determined using a validated HPLC-DAD assay. Pharmacokinetic parameters were determined using the compartment model technique. All experiments were carried out in triplicate.
 Results: The pharmacokinetic parameters of 3CBB obtained were as follows: Tmax= 28.9±1.1 min, Cmax = 0.57±0.02 µg/ml, AUCtotal = 66.3±1.0 µg min/ml, Kel = 0.018±0.002 min-1, and T1/2el = 39.4±3.9 min. The long elimination half-life and low Cmax indicated that 3CBB was extensively distributed in the deep and very deep tissues. This confirmed the unique and special characteristics of a highly lipophilic compound like 3CBB (log P = 3.73).
 Conclusion: 3CBB demonstrated a slower onset of action and longer elimination time from the body compared to ASA. Thus this new compound is a potential candidate to be developed as a new drug.

Novel Pyrene Excimer and Fluorogenic Probe for the Detection of Alkylating Agents.

A pyrene-containing salicylic acid derivative (4) was found to be low in fluorescence, but its derivative pyrene-containing methyl salicylate (3) was found to be highly fluorescent in aqueous solution. This derivative has been tested in solution and found to be superior in the fluorogenic assay of pharmaceutical compounds, detection of chemical warfare agents, a preliminary toxicology test, mutagenicity of medicinal compounds, and other chemical analyses, including trimethylsilyl diazomethane; alkyl bromides and iodides; a sulfur mustard mimic 2-chloroethyl ethyl sulfide; and anticancer drugs, busulfan and pipobroman. The salicylic acid derivative (4) was applied as a fluorogenic probe for the detection of alkylating agents by esterification and generating fluorescence at 475 nm in solutions at low concentrations.

Rhizosphere microbiomes diverge among Populus trichocarpa plant-host genotypes and chemotypes, but it depends on soil origin

BackgroundPlants have developed defense strategies for phytopathogen and herbivore protection via coordinated metabolic mechanisms. Low-molecular weight metabolites produced within plant tissues, such as salicylic acid, represent one such mechanism which likely mediates plant – microbe interactions above and below ground. Salicylic acid is a ubiquitous phytohormone at low levels in most plants, yet are concentrated defense compounds in Populus, likely acting as a selective filter for rhizosphere microbiomes. We propagated twelve Populus trichocarpa genotypes which varied an order of magnitude in salicylic acid (SA)-related secondary metabolites, in contrasting soils from two different origins. After four months of growth, plant properties (leaf growth, chlorophyll content, and net photosynthetic rate) and plant root metabolomics specifically targeting SA metabolites were measured via GC-MS. In addition, rhizosphere microbiome composition was measured via Illumina MiSeq sequencing of 16S and ITS2 rRNA-genes.ResultsSoil origin was the primary filter causing divergence in bacterial/archaeal and fungal communities with plant genotype secondarily influential. Both bacterial/archaeal and fungal evenness varied between soil origins and bacterial/archaeal diversity and evenness correlated with at least one SA metabolite (diversity: populin; evenness: total phenolics). The production of individual salicylic acid derivatives that varied by host genotype resulted in compositional differences for bacteria /archaea (tremuloidin) and fungi (salicylic acid) within one soil origin (Clatskanie) whereas soils from Corvallis did not illicit microbial compositional changes due to salicylic acid derivatives. Several dominant bacterial (e.g., Betaproteobacteria, Acidobacteria, Verrucomicrobia, Chloroflexi, Gemmatimonadete, Firmicutes) and one fungal phyla (Mortierellomycota) also correlated with specific SA secondary metabolites; bacterial phyla exhibited more negative interactions (declining abundance with increasing metabolite concentration) than positive interactions.ConclusionsThese results indicate microbial communities diverge most among soil origin. However, within a soil origin, bacterial/archaeal communities are responsive to plant SA production within greenhouse-based rhizosphere microbiomes. Fungal microbiomes are impacted by root SA-metabolites, but overall to a lesser degree within this experimental context. These results suggest plant defense strategies, such as SA and its secondary metabolites, may partially drive patterns of both bacterial/archaeal and fungal taxa-specific colonization and assembly.

Stereoselective synthesis of new type of estradiol hybrid molecules and their antiproliferative activities

To prepare new type of estrane hybrid molecules, we chose 3-methoxy- and 3-benzyloxy-17β,16β-epoxymethylene-estra-1,3,5(10)-trienes as starting materials (2 and 5). These steroid oxetanes were transformed with ethylene glycol in the presence of BF3.OEt2 into 3-methoxy- and 3-benzyloxy-16β-(2′-oxa-4′-hydroxy)butyl-17β-hydroxy-estra-1,3,5(10)-trien-17β-ols (3a and 6a). Iodination of the terminal hydroxy group afforded iodo derivatives 3b and 6b, which underwent one-pot 3-O-alkylation with unprotected ascorbic acid to yield 3c and 6c. The same process with salicylic acid led to 2-O-alkylated salicylic acid derivatives 3d and 6d. Iodo derivatives 3b and 6b underwent nucleophilic exchange reaction with NaN3 furnishing the corresponding azido compounds 3e and 6e. These compounds were subjected to azide–alkyne CuAAC reactions with phenylacetylene and their p-substituted derivatives to form 1,4-substituted triazoles 3f-h and 6f-h. The reduction of 3e and 6e with hydrazine hydrate in the presence of Raney Ni provided the corresponding amino derivatives 3i and 6i. These compounds were reacted further with varied substituted benzoic acids to deliver terminal benzamido derivatives 3j-m and 6j-m.We determined the in vitro antiproliferative activities of compounds 2, 5, 3a-m and 6a-m by means of MTT assays on a panel of human adherent cancer cell lines A2780, MCF-7, MB-231 and SiHa.

Effects of aspirin on aquaponics tomato (Solanumly copersicum) production in laboratory condition

The experiment was conducted to visualize the effect of exogenous aspirin on tomato production in aquaponic system. Aspirin, a derivative of salicylic acid, acts as a potential non-enzymatic antioxidant and plant growth promoter, hence regulates plant physiology. The experiment employed three treatments (T) with three replications (R) each where, 60 ppm and 120 ppm aspirin were used in T1 and T2, respectively and Tcon was control with no aspirin. Media filled plastic containers (0.29m×0.30m×0.21m) as growbeds and plastic tanks of 120 liter capacity as fish tank were installed to construct each aquaponic systems indicating each replication. Tilapia, was stocked at 111 fish /m3 in the fish tank and fed commercial floating feed containing 30% protein at the rate of 3% body weight twice daily. In each replication, two tomato saplings were planted. Fish tank water was oxygenated with a 10 watt air pump, then waste water from tank was pumped to grow bed with a 12 watt submersible pump. Survival rates were 70, 85 and 50% in T1, T2 and Tcon respectively. While fish productions were 0.42, 0.34 and 40.49 (kg/m2/60 days) in T1, T2 and Tcon respectively. The water quality parameters were within the suitable ranges for tilapia as well as tomato in the aquaponic system. Foliar spray of aspirin was applied fortnightly. Tomato production was hampered with various diseases in all the treatments although the aspirin treated plant (T1 and T2) were free from few diseases. The highest tomato production was found 0.44 kg/m2/60 days in T2 followed by T1 (0.42 kg/m2/60 days) and Tcon (0.34 kg/m2/60 days). Noticeably, Plant growth and tomato production were higher in T2 and T1 with less disease prevalence than Tcon, suggesting positive impacts of aspirin on tomato. However, further research is needed to justify the aspirin doses at user level.
 Asian J. Med. Biol. Res. March 2019, 5(1): 78-86

Study of formation of valuable organic products from bioremediation of chlorpyrifos by bacteria catalyzed by molybdenum and zinc salt

Experimental studies have been carried out to find the bioremediation activity of bacteria with molybdenum and zinc ions separately on the toxic insecticide, chlorpyrifos. Two bacterial strains, ZS20 (Enterobacter sp. strain TSNG) and E57 (Pseudomonas sp. strain GRTM) and three inorganic salts: ammonium-molybdate, sodium-molybdate, and zinc-nitrate, have been used for the degradation of toxic insecticide, chlorpyrifos. The metabolic products obtained are chelating organic acids, such as maleamic acid, ascorbic acid, salicylic acid, and other different derivatives of soluble-phosphate and phosphatase enzymes. They help for the better growth of plants. Ammonium-molybdate along with ZS20 strain is more active for the production of metabolic products and the growth of plants than the other combination. The liquid chromatography and mass spectrometry data of ZS20 and ammonium-molybdate salt portray complete degradation of chlorpyrifos into nontoxic valuable products. Hence, this combination can be used as good bioremediater as well as good biofertilizer. Results have been tabulated, shown graphically and discussed.

Synthesis, experimental and theoretical photophysical study of proton transfer based oxazoline fluorophores. Potential tailor made optical sensors for enantiomeric detection in solution

A series of oxazoline based compounds was obtained via amidation formation from salicylic acid derivatives and benzyl-protected l-threonine with good yields (50–90%). These compounds present absorption in the UV region (∼300 nm) and fluorescence emission spectra show large Stokes shift emission (∼10000 cm−1) in the blue-green region attributed to the ESIPT process. TD-DFT calculations were carried out to investigate the process of proton transfer of the structure of both tautomers (keto and enol) and corroborating the UV region absorption and large Stokes shift. The oxazolines derivatives were investigated as optical sensor for enantiomeric identification in solution. Preliminary results indicate sensing for arabinose and tartaric acid, but not specificity. However, to the pair R-(−)-Mandelic and S-(+)-Mandelic acid, the oxazoline 4c showed a enantiomeric selectivity identification, allowing to envisage these compounds as potential photoactive building blocks to propose innovative optical sensors in solution.

Non steroidal anti-inflammatory drug (NSAIDs) in breast cancer chemotherapy; antimony(V) salicylate a DNA binder

The organoantimony(V) derivative of salicylic acid (SalH2), {[Ph3Sb(SalH)]2O} (SalOSbi) was synthesized and tested for its anti-proliferative activity. SalOSbi was characterized by melting point and FT-IR, 1H NMR, Uv–Vis spectroscopic techniques. Its crystal and molecular structure is also determined by single-crystal X-ray diffraction crystallography.The antiproliferative activity of SalOSbi against human breast cancer cells: MCF-7 (Hormone Dependent (HD)) and MDA-MB-231 (Hormon Independent (HI) is congener or better than that of cisplatin. However SalOSbi is less toxic (by 7-fold) against human lung embryonic fibroblast cells (MRC-5), than cisplatin. Micronucleus assay shows that SalOSbi demonstrates similar in vitro genotoxicity with cisplatin against MRC-5 cells. The apoptotic type of cells death, caused by SalOSbi, was studied by cell cycle arrest and permeabilization of the mitochondrial membrane test. Electronic spectroscopic data confirm strong covalent binding of SalOSbi with DNA, through N(purine or pyrimidine)-M bonds in a similar manner to cisplatin. No inhibitory interaction with lipoxygenase (LOX) has been detected suggesting the non-involvement of the mitochondrial apoptotic pathway.

A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants.

In this study, a series of salicylic acid derivatives were designed and synthesized as novel non-saccharide α-glucosidase inhibitors. Biological evaluation indicated that when compared to acarbose, compounds T9, T10, and T32 exhibited a higher potency of α-glucosidase inhibitory activity with IC50 values of 0.15 ± 0.01, 0.086 ± 0.01 and 0.32 ± 0.02 mM, respectively. Evaluation of the inhibition kinetics indicated that T9, T10, T32, and acarbose interacted with α-glucosidase in a mixed non-competitive inhibitory manner. Moreover, T9, T10, and T32 statically quenched the fluorescence of α-glucosidase by formation of an inhibitor-α-glucosidase complex. The docking results showed that hydrogen bonds were generated between the test compounds and α-glucosidase. The antioxidant study revealed that compound T10 exhibited a higher antioxidant activity via scavenging 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), thereby inhibiting lipid peroxidation and the total reduction capacity. In brief, the salicylic acid derivatives identified in this study were promising candidates for development as novel non-saccharide α-glucosidase inhibitors.

A novel mechanism for the anticancer activity of aspirin and salicylates.

Epidemiological studies indicate that long-term aspirin usage reduces the incidence of colorectal cancer (CRC) and may protect against other non-CRC associated adenocarcinomas, including oesophageal cancer. A number of hypotheses have been proposed with respect to the molecular action of aspirin and other non-steroidal anti-inflammatory drugs in cancer development. The mechanism by which aspirin exhibits toxicity to CRC has been previously investigated by synthesising novel analogues and derivatives of aspirin in an effort to identify functionally significant moieties. Herein, an early effect of aspirin and aspirin-like analogues against the SW480 CRC cell line was investigated, with a particular focus on critical molecules in the epidermal growth factor (EGF) pathway. The present authors proposed that aspirin, diaspirin and analogues, and diflunisal (a salicylic acid derivative) may rapidly perturb EGF and EGF receptor (EGFR) internalisation. Upon longer incubations, the diaspirins and thioaspirins may inhibit EGFR phosphorylation at Tyr1045 and Tyr1173. It was additionally demonstrated, using a qualitative approach, that EGF internalisation in the SW480 cell line may be directed to endosomes by fumaryldiaspirin using early endosome antigen 1 as an early endosomal marker and that EGF internalisation may also be perturbed in oesophageal cell lines, suggestive of an effect not only restricted to CRC cells. Taken together and in light of our previous findings that the aspirin-like analogues can affect cyclin D1 expression and nuclear factor-κB localisation, it was hypothesized that aspirin and aspirin analogues significantly and swiftly perturb the EGFR axis and that the protective activity of aspirin may in part be explained by perturbed EGFR internalisation and activation. These findings may also have implications in understanding the inhibitory effect of aspirin and salicylates on wound healing, given the critical role of EGF in the response to tissue trauma.

Antiproliferative effects of zerumbone-pendant derivatives on human T-cell lymphoid cell line Jurkat cells

Zerumbone is the major component of the essential oil of wild ginger, Zingiber zerumbet Smith. It is not only highly reactive but also has diverse bioactivities. Those effects derive from two conjugated double bonds of zerumbone and a carbonyl group in between, and we had already established a synthetic scheme for zerumbone-pendant derivatives without disturbing the conjugation system. Herein, twelve conjugates with salicylic acid or various benzoic acid derivatives were synthesized for evaluations of their antiproliferative effects on Jurkat cells as salicylic acid is bioactive and has a carboxylic group for coupling. Most of them resulted in IC50 values as low as 1–10 μM, validating the utility of this activity-conserving strategy.

Design, synthesis and biological evaluation of tryptamine salicylic acid derivatives as potential antitumor agents.

A series of tryptamine salicylic acid derivatives were synthesized and their antiproliferative activity against MGC-803, MCF-7, HepG2, A549 and HeLa cell lines was evaluated. The structure-activity relationship (SAR) study revealed that different substitutions of the C5 and C3'-C5' positions have certain effects on the anti-proliferation activity. The growth assay revealed that N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide (E20) showed the most potent and broad-spectrum anticancer inhibition of all the cell lines evaluated, and was only more potent than 5-Fu for the gastric cancer cell line. Preliminary studies indicated that compound E20 could inhibit colony formation and migration of MGC-803 cells. The flow cytometry (FCM) results showed that compound E20 arrested the cell cycle in the G2/M phase and induced apoptosis of MGC-803 cells in a concentration-dependent manner. In addition, the western blot results showed that E20 can down-regulate the expression of hexokinase 2. Our studies suggest that the framework of N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide may be consider as a new type of chemical for designing effective anti-cancer drugs targeting gastric cancer cells.

Synthesis and Anticancer Activity Evaluation of Hydrolyzed Derivatives of Panaxnotoginseng Saponins.

To increase the antitumor activity of ginsenosides and acetylsalicylic acid, acid hydrolysis products of Panaxnotoginseng saponin were used as raw materials to be combined with salicylic acid to obtain ginsenoside salicylic acid derivatives. All derivatives were assessed for anti-cancer activity. A total of 20 target compounds were designed and synthesized. The cytotoxic activity on five cancer cell lines, including human colon cancer (HT-29), gastric cancer (BGC-823), cervical cancer (Hela), human breast cancer (MCF-7), human lung cancer cells (A549), and two normal cancer cell lines (human gastric epithelial cells (GES-1), and human ovarian epithelial cells (IOSE144)) was evaluated following treatment with the compounds. The results showed that all compounds inhibited the growth of cancer cells. Compounds 1a, 3a, 7a, 1b, 2b, 3b and 8b showed strong anticancer activity. For MCF-7 cells, compound 3b showed the strongest inhibitory activity, IC50 = 2.56 ± 0.09 μM. In the cytotoxicity test, all compounds showed low toxicity or no toxicity (IC50 > 100 μM). In addition, a cell cycle distribution assay and wound healing assay demonstrated that compound 3b specifically inhibited MCF-7 proliferation and migration ability. Our results indicate that compound 3b represents a promising compound for further cancer studies.

Silica–Titania Sol–Gel Materials: Synthesis and Analytical Applications

Data on the synthesis of silica–titania sol–gel materials and their analytical applications as new sensor materials obtained by the author are generalized. The methods of the synthesis of silica–titania xerogels with specified textural characteristics are considered. Data on heterogeneous complexation and redox reactions with the participation of silica–titania xerogels are reported. The new sensor materials based on silica–titania xerogels were used for the development of procedures for the solid-phase spectrophotometric determination of hydrogen peroxide, ascorbic acid, polyphenols, salicylic acid derivatives, and fluoride and oxalate ions and for the test determination of hydrogen peroxide and propyl gallate. The results of the application of the developed procedures to the analysis of food, pharmaceutical preparations, hygienic products, and biological liquids are given.

Low-dose daily aspirin reduces topical minoxidil efficacy in androgenetic alopecia patients.

Topical minoxidil is the only US FDA approved OTC drug for the treatment of androgenetic alopecia (AGA). Minoxidil is a pro-drug converted into its active form, minoxidil sulfate, by the sulfotransferase enzymes in the outer root sheath of hair follicles. Previously, we demonstrated that sulfotransferase activity in hair follicles predicts response to topical minoxidil in the treatment of AGA. In the human liver, sulfotransferase activity is significantly inhibited by salicylic acid. Low-dose OTC aspirin (75-81 mg), a derivative of salicylic acid, is used by millions of people daily for the prevention of coronary heart disease and cancer. It is not known whether oral aspirin inhibits sulfotransferase activity in hair follicles, potentially affecting minoxidil response in AGA patients. In the present study, we determined the follicular sulfotransferase enzymatic activity following 14 days of oral aspirin administration. In our cohort of 24 subjects, 50% were initially predicted to be responders to minoxidil. However, following 14 days of aspirin administration, only 27% of the subjects were predicted to respond to topical minoxidil. To the best of our knowledge, this is the first study to report the effect of low-dose daily aspirin use on the efficacy of topical minoxidil.

Salicylic acid and its derivatives elicit the production of diterpenes and sterols in corals and their algal symbionts: a metabolomics approach to elicitor SAR

The production of marine drugs in its normal habitats is often low and depends greatly on ecological conditions. Chemical synthesis of marine drugs is not economically feasible owing to their complex structures. Biotechnology application via elicitation represents a promising tool to enhance metabolites yield that has yet to be explored in soft corals. Study the elicitation impact of salicylic acid (SA) and six analogues in addition to a systemic acquired resistance inducer on secondary metabolites accumulation in the soft coral Sarcophyton ehrenbergi along with the symbiont zooxanthellae and if SA elicitation effect is extended to other coral species S. glaucum and Lobophyton pauciliforum. Post elicitation in the three corals and zooxanthella, metabolites were extracted and analyzed via UHPLC-MS coupled with chemometric tools. Multivariate data analysis of the UHPLC-MS data set revealed clear segregation of SA, amino-SA, and acetyl-SA elicited samples. An increased level ca. 6- and 8-fold of the diterpenes viz., sarcophytonolide I, sarcophine and a C28-sterol, was observed in SA and amino-SA groups, respectively. Post elicitation, the level of diepoxy-cembratriene increased 1.5-fold and 2.4-fold in 1mM SA, and acetyl-SA (aspirin) treatment groups, respectively. S. glaucum and Lobophyton pauciliforum showed a 2-fold increase of diepoxy-cembratriene levels. These results suggest that SA could function as a general and somewhat selective diterpene inducing signaling molecule in soft corals. Structural consideration reveals initial structure-activity relationship (SAR) in SA derivatives that seem important for efficient diterpene and sterol elicitation.

A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by activating autophagy and the mitochondrial unfolded protein response.

Plant extracts containing salicylates are probably the most ancient remedies to reduce fever and ease aches of all kind. Recently, it has been shown that salicylates activate adenosine monophosphate‐activated kinase (AMPK), which is now considered as a promising target to slow down aging and prevent age‐related diseases in humans. Beneficial effects of AMPK activation on lifespan have been discovered in the model organism Caenorhabditis elegans (C. elegans). Indeed, salicylic acid and acetylsalicylic acid extend lifespan in worms by activating AMPK and the forkhead transcription factor DAF‐16/FOXO. Here, we investigated whether another salicylic acid derivative 5‐octanoyl salicylic acid (C8‐SA), developed as a controlled skin exfoliating ingredient, had similar properties using C. elegans as a model. We show that C8‐SA increases lifespan of C. elegans and that a variety of pathways and genes are required for C8‐SA‐mediated lifespan extension. C8‐SA activates AMPK and inhibits TOR both in nematodes and in primary human keratinocytes. We also show that C8‐SA can induce both autophagy and the mitochondrial unfolded protein response (UPRmit) in nematodes. This induction of both processes is fully required for lifespan extension in the worm. In addition, we found that the activation of autophagy by C8‐SA fails to occur in worms with compromised UPRmit, suggesting a mechanistic link between these two processes. Mutants that are defective in the mitochondrial unfolded protein response exhibit constitutive high autophagy levels. Taken together, these data therefore suggest that C8‐SA positively impacts longevity in worms through induction of autophagy and the UPRmit.