Salicylic Acid Derivatives Research Articles

Anacardic Acid Constituents from Cashew Nut Shell Liquid: NMR Characterization and the Effect of Unsaturation on Its Biological Activities.

Anacardic acids are the main constituents of natural cashew nut shell liquid (CNSL), obtained via the extraction of cashew shells with hexane at room temperature. This raw material presents high technological potential due to its various biological properties. The main components of CNSL are the anacardic acids, salicylic acid derivatives presenting a side chain of fifteen carbon atoms with different degrees of unsaturation (monoene–15:1, diene–15:2, and triene–15:3). Each constituent was isolated by column chromatography using silica gel impregnated with silver nitrate. The structures of the compounds were characterized by nuclear magnetic resonance through complete and unequivocal proton and carbon assignments. The effect of the side chain unsaturation was also evaluated in relation to antioxidant, antifungal and anticholinesterase activities, and toxicity against Artemia salina. The triene anacardic acid provided better results in antioxidant activity assessed by the inhibition of the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), higher cytotoxicity against A. salina, and acetylcholinesterase (AChE) inhibition. Thus, increasing the unsaturation of the side chain of anacardic acid increases its action against free radicals, AChE enzyme, and A. salina nauplii. In relation to antifungal activity, an inverse result was obtained, and the linearity of the molecule plays an important role, with monoene being the most active. In conclusion, the changes in structure of anacardic acids, which cause differences in polarity, contribute to the increase or decrease in the biological activity assessed.

Effect of nonionic micelles of Triton X-100 on protonation equilibria of salicylic acid derivatives

Effect of nonionic micelles of Triton X-100 on protonation equilibria of salicylic acid derivatives

A new fluorogenic sensing platform for salicylic acid derivatives based on π-π and NH-π interactions between electron-deficient and electron-rich aromatics

A novel simple fluorescent probe was designed for the recognition of electron-rich salicylic acid derivatives (SAs). The imidazole-appended aminomethyl perylene probe 1 selectively differentiated between electron-rich amino-SAs and electron-deficient nitro-SAs in EtOH, exhibiting the highest selectivity and sensitivity toward 5-aminosalicylic acid (5-ASA) and showing strong 1:1 binding (Ka=1.37×107M−1). This high selectivity and sensitivity resulted from the synergistic multiple hydrogen bonding interactions of secondary amine and imidazole units and π-π interactions between electron-rich and electron-deficient rings, along with the unusual NH-π interactions between 5-ASA and the perylene moiety of 1. The limit of detection (LOD) for 5-ASA in EtOH was 0.012ppb.

Analgesic Activity Test 2- (3- (chloromethyl) Benzoiloksi) Benzoate and 2- (4- (chloromethyl) Benzoiloksi) Benzoate on Male Wistar Rats with Plantar Test Method

The new compounds of salicylic acid derivatives, 2- (3- (chloromethyl) benzoiloksi)benzoic acid and 2-(4-(chloromethyl)benzoiloksi) benzoate was synthesized to produce a greater analgesic activity and lower stomach irritation from salicylic acid. 2-(4-(chloromethyl) benzoiloksi)benzoic acid and 2-(3-(chloromethyl)benzoiloksi) benzoate was synthesized by Schotten-Baumann acylation reaction. In this study, the analgesic test activity with plantar test method. The compound was given to test animals in doses of 12.5; 25; 50; 100; and 200 mg.kg-1. Analgesic activity was determined by the response time of mice to pain infra-red heat. The percentage is calculated by the mean pain barrier time response to pain. The results showed percentation of pain barrier: 74.28%; 105.58%; 110.58%; 115.29%; and 175.87% after administration of the compound 2-(4-(chloromethyl) benzoiloksi) benzoate at doses of 12.5; 25; 50; 100; and 200 mg.kg-1, respectively. The results of calculations percent pain barrier 2-(3-(chloromethyl)benzoiloksi) benzoate, obtained 85.30%; 92.48%; 124.96%; 180.36%; and 208.01% consecutive for the doses compound of 12.5; 25; 50; 100; and 200 mg.kg-1. Five doses of acetyl salicylic acid ranging from 12.5 mg. kg-1 to 200 mg.kg-1 resulted in percent pain barrier as follows: 26%; 34.34%; 45.68%; 60.38% and 114.12%. This study indicates that 2-(3-(chloromethyl)benzoiloksi)benzoic acid and 2-(4-(chloromethyl)benzoiloksi) benzoate are capable of producing higher analgesic activity than acetyl salicylic acid. Keywords: analgesic, benzoate, plantar test method

Synthesis and photoprotective properties of new salicylic and vanillic acid derivatives

Synthesis and photoprotective properties of new salicylic and vanillic acid derivatives

Synthesis and characterization of mixed ligand Cu(II) complexes of salicylic acid derivatives with 2-aminobenzotiyazol derivatives

Synthesis and characterization of mixed ligand Cu(II) complexes of salicylic acid derivatives with 2-aminobenzotiyazol derivatives

Untargeted metabolomics analysis reveals dynamic changes in azelaic acid- and salicylic acid derivatives in LPS-treated Nicotiana tabacum cells

To counteract biotic stress factors, plants employ multilayered defense mechanisms responsive to pathogen-derived elicitor molecules, and regulated by different phytohormones and signaling molecules. Here, lipopolysaccharide (LPS), a microbe-associated molecular pattern (MAMP) molecule, was used to induce defense responses in Nicotiana tabacum cell suspensions. Intracellular metabolites were extracted with methanol and analyzed using a liquid chromatography-mass spectrometry (UHPLC-qTOF-MS/MS) platform. The generated data were processed and examined with multivariate and univariate statistical tools. The results show time-dependent dynamic changes and accumulation of glycosylated signaling molecules, specifically those of azelaic acid, salicylic acid and methyl-salicylate as contributors to the altered metabolomic state in LPS-treated cells.

Computational design of novel inhibitors to overcome weed resistance associated with acetohydroxyacid synthase (AHAS) P197L mutant.

Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) is the first common enzyme in the biosynthetic pathway leading to the branched-chain amino acids in plants and a wide range of microorganisms. With the long-term and wide application of AHAS inhibitors, weed resistance is becoming a global problem, which leads to an urgent demand for novel inhibitors to antagonize both wild-type and resistant AHAS. Pyrimidinyl salicylic acid derivatives, as one of the main classes of commercial AHAS herbicides, show potential anti-resistant bioactivity to wild-type and P197L mutant. In current work, a series of novel 2-benzoyloxy-6-pyrimidinyl salicylic acid derivatives were designed through fragment-based drug discovery. Fortunately, the newly synthesized compounds showed good inhibitory activity against both wild-type and P197L mutant. Some compounds not only had a lower resistance factor value but also showed excellent inhibitory activity against wild-type AHAS and P197L mutant. Furthermore, greenhouse experiments showed compound 11m displayed almost 100% inhibition against both wild-type and high-resistant Descurainia sophia at a dosage of 150 g a.i. ha-1 . The present work indicated that the 2-benzoyloxy-6-pyrimidinyl salicylic acid motif was well worth further optimization. Also, compound 11m could be used as a potential anti-resistant AHAS herbicide, which requires further research. © 2016 Society of Chemical Industry.

Metal-Free Oxidative Coupling of Benzylamines to Imines under an Oxygen Atmosphere Promoted Using Salicylic Acid Derivatives as Organocatalysts.

The oxidative coupling of benzylamines proceeds efficiently using salicylic acid derivatives as organocatalysts under an oxygen atmosphere, affording the corresponding N-benzylidenebenzylamines in high yields. Electron-rich salicylic acid derivatives such as 4,6-dimethoxysalicylic acid and 4,6-dihydroxysalicylic acid exhibit excellent catalytic activities for the oxidative coupling of benzylamines to give the corresponding imines. This amine oxidation can also be applied to the synthesis of nitrogen-containing heterocycles such as benzimidazole derivatives. Furthermore, to recycle the catalyst, silica gel supported with 4.7 wt % of 4,6-dihydroxysalicylic acid is prepared, which acts as a recyclable catalyst, oxidizing benzylamine to imine four times successfully.

Life traits of four Botryosphaeriaceae species and molecular responses of different grapevine cultivars or hybrids

Botryosphaeriaceae is a fungal family comprising many species involved in botryosphaeria dieback, a worldwide grapevine trunk disease. Currently, the interactions between Botryosphaeriaceae species and various grapevine cultivars are poorly understood and little data is available. This study investigated various life traits of five isolates belonging to four species of Botryosphaeriaceae found in French vineyards (Diplodia mutila, Diplodia seriata, Lasiodiplodia viticola and Neofusicoccum parvum). The two species N. parvum and L. viticola exhibited the highest optimal growth temperature and the best growth rates. They were also responsible for the most extensive necrosis and cankers in three Vitis vinifera cultivars (Cabernet Sauvignon, Merlot and Ugni‐Blanc) that differed in susceptibility to botryosphaeria dieback, and in two genotypes resistant to downy and powdery mildew (RV4 and RV5). Identification of the extracellular toxins produced by isolates in culture media showed that the N. parvum isolate had a different metabolite profile from the others, producing terremutin and salicylic acid derivatives, which are known to be compounds associated with virulence. In a second step, life traits were associated with nondestructive monitoring of gene expression involved in the defence mechanisms of five grapevine cultivars and genotypes after inoculation of wood cuttings with Botryosphaeriaceae. The transcript analyses were carried out at different times and were associated with principal component analysis (PCA). Each cultivar presented a specific transcript signature and several transcripts were correlated either with the size of necrosis/cankers or with symptom reduction, thus offering useful markers for breeding or estimating the defence status of plants.

Polyfluorinated salicylic acid derivatives as analogs of known drugs: Synthesis, molecular docking and biological evaluation

We have developed the convenient methods for synthesis of polyfluorosalicylic acids and their derivatives. For the first time the biological properties of polyfluorosalicylates were investigated in vitro (permeability through the biological membranes, COX-1 inhibitory action) and in vivo (anti-inflammatory, analgesic activities, acute toxicity). Molecular docking of polyfluorinated salicylates confirmed in vitro and in vivo experiments.

The influence of systemic inducing agents on horse chestnut leaf miner (Cameraria ohridella) severity in white flowering horse chestnut (Aesculus hoppicastanum L.)

Two separate trials during 2010 and 2011 were conducted using field grown white flowering horse chestnut trees (Aesculus hippocastanum L.) to asssess the insecticidal efficacy of three systemic inducing agents (SIR), namely (Messanger (active substance (a.s.) Harpin protein), Phoenix (a.s. Potassium phosphite) and Rigel (a.s. Salicylic acid derivative) applied to coincide with the appearance of each adult generation of the insect pest, horse chestnut leaf miner (Cameraria ohridella Deschka and Dimic; HCLM). A conventional synthetic insecticide (deltamethrin) used within the UK for HCLM control was included for comparison. A marked impact of SIR inducing agent and frequency of application on HCLM severity was recorded. The effectiveness of each SIR inducing agent on mean number of HCLM mines per leaf and percent HCLM larvae/pupae mortality increased when applied at increasing frequencies i.e. three sprays provided greater control than two sprays while two sprays provided greater control than one spray. The synthetic insecticide deltamethrin provided the greatest degree of HCLM control with two foliar sprays providing 100% HCLM control. Efficacy of SIR inducing agents based on reduction of HCLM mines per leaf after three sprays averaged across both the 2010 and 2011 growing seasons was in the order potassium phosphite>salicylic acid derivative>harpin protein>water control where leaf mining activity was reduced by 35–64%. Enhancement of leaf phenolic content was indicated as a means by which SIR agents reduced leaf mining activity. Results show commercially available SIR inducing agents exist that provide potentially acceptable degrees of HCLM control provided at least two sprays are applied during a growing season.

Polymeric prodrug⿿functionalized polypropylene films for sustained release of salicylic acid

Medical devices decorated with salicylic acid-based polymer chains (polymeric prodrug) that slowly release this anti-inflammatory and anti-biofilm drug at the implantation site were designed. A ⿿grafting from⿿ method was implemented to directly grow chains of a polymerizable derivative of salicylic acid (2-methacryloyloxy-benzoic acid, 2MBA) onto polypropylene (PP). PP was modified both at bulk and on the surface with poly(2MBA) by means of an oxidative pre-irradiation method (60Co source), in order to obtain a grafted polymer in which salicylic acid units were linked by means of labile ester bonds. The grafting percent depended on absorbed dose, reaction time, temperature and monomer concentration. The functionalized films were analyzed regarding structure (FTIR-ATR, SEM-EDX, fluorescence microscopy), temperature stability (TGA), interaction with aqueous medium (water contact angle and swelling), pH-responsive release and cytocompatibility (fibroblasts). In the obtained poly(2MBA)-grafted biomaterial, poly(2MBA) behaved as a polymeric prodrug that regulates salicylic acid release once in contact with aqueous medium, showing pH-dependent release rate.

UJI AKTIVITAS ANALGESIK ASAM 2-(3-(KLOROMETIL)BENZOILOKSI)BENZOAT DAN ASAM 2-(4-(KLOROMETIL)BENZOILOKSI)BENZOAT PADA TIKUS WISTAR JANTAN DENGAN METODE PLANTAR TEST

The new compounds of salicylic acid derivatives, 2- (3- (chloromethyl) benzoyloxy) benzoic acid and 2- (4- (chloromethyl) benzoyloxy) benzoic acid were synthesized to generate better analgesic activity and lesser stomach irritation of salicylic acid. The 2- (4- (chloromethyl) benzoyloxy) benzoic acid and 2- (3- (chloromethyl) benzoiloksi) benzoic acid were synthesized by Schotten-Baumann acylation process. In this study, analgesic activity was tested by plantar test method. The compounds were administered to the tested animals at 12.5; 25; 50; 100; and 200 mg / kg BW of doses. Analgesic activity was determined by the response time of rat to pain induced by infra red. The percentage of pain hindrance was calculated from the mean of response time to pain. Pain hindrance percentage were shown as: 74 . 28%; 105 . 58%; 110.58%; 115 . 29%; and 175 . 87% after administration of 2- (4- (chloromethyl) benzoyloxy) benzoic acid at doses of 12.5; 25; 50; 100; and 200 mg / kg. The pain hindrance percentage after administration of 2- (3- (chloromethyl) benzoyloxy) benzoaic acid, were 85 . 30%; 92 . 48%; 124 . 96%; 180 . 36%; and 208 . 01% respective to the doses of 12 . 5; 25; 50; 100; and 200 mg / kg. Five doses of acetyl salicylic acid ranged from 12.5 mg / kg to 200 mg / kg showed pain hindrance percentage as: 26%; 34 . 34%; 45 . 68%; 60 . 38%; and 114 . 12%. This study indicated that 2- (3- (chloromethyl) benzoyloxy) benzoic acid and 2- (4- (chloromethyl) benzoyloxy) benzoic acid generated higher analgesic activity than acetyl salicylic acid.

Uji Aktivitas Analgesik Asam 2-(3-(Klorometil)Benzoiloksi)Benzoat dan Asam 2-(4-(Klorometil)Benzoiloksi)Benzoat Pada Tikus Wistar Jantan dengan Metode Plantar Test

The new compounds of salicylic acid derivatives, 2- (3- (chloromethyl) benzoyloxy) benzoic acid and 2- (4- (chloromethyl) benzoyloxy) benzoic acid were synthesized to generate better analgesic activity and lesser stomach irritation of salicylic acid. The 2- (4- (chloromethyl) benzoyloxy) benzoic acid and 2- (3- (chloromethyl) benzoiloksi) benzoic acid were synthesized by Schotten-Baumann acylation process. In this study, analgesic activity was tested by plantar test method. The compounds were administered to the tested animals at 12.5; 25; 50; 100; and 200 mg / kg BW of doses. Analgesic activity was determined by the response time of rat to pain induced by infra red. The percentage of pain hindrance was calculated from the mean of response time to pain. Pain hindrance percentage were shown as: 74.28%; 105.58%; 110.58%; 115.29%; and 175.87% after administration of 2- (4- (chloromethyl) benzoyloxy) benzoic acid at doses of 12.5; 25; 50; 100; and 200 mg / kg. The pain hindrance percentage after administration of 2- (3- (chloromethyl) benzoyloxy) benzoaic acid, were 85.30%; 92.48%; 124.96%; 180.36%; and 208.01% respective to the doses of 12.5; 25; 50; 100; and 200 mg / kg. Five doses of acetyl salicylic acid ranged from 12.5 mg / kg to 200 mg / kg showed pain hindrance percentage as: 26%; 34.34%; 45.68%; 60.38%; and 114.12%. This study indicated that 2- (3- (chloromethyl) benzoyloxy) benzoic acid and 2- (4- (chloromethyl) benzoyloxy) benzoic acid generated higher analgesic activity than acetyl salicylic acid.

Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.

Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

Benzoylsalicylic acid isolated from seed coats of Givotia rottleriformis induces systemic acquired resistance in tobacco and Arabidopsis

Systemic acquired resistance (SAR), a whole plant defense response to a broad spectrum of pathogens, is characterized by a coordinated expression of a large number of defense genes. Plants synthesize a variety of secondary metabolites to protect themselves from the invading microbial pathogens. Several studies have shown that salicylic acid (SA) is a key endogenous component of local and systemic disease resistance in plants. Although SA is a critical signal for SAR, accumulation of endogenous SA levels alone is insufficient to establish SAR. Here, we have identified a new acyl derivative of SA, the benzoylsalicylic acid (BzSA) also known as 2-(benzoyloxy) benzoic acid from the seed coats of Givotia rottleriformis and investigated its role in inducing SAR in tobacco and Arabidopsis. Interestingly, exogenous BzSA treatment induced the expression of NPR1 (Non-expressor of pathogenesis-related gene-1) and pathogenesis related (PR) genes. BzSA enhanced the expression of hypersensitivity related (HSR), mitogen activated protein kinase (MAPK) and WRKY genes in tobacco. Moreover, Arabidopsis NahG plants that were treated with BzSA showed enhanced resistance to tobacco mosaic virus (TMV) as evidenced by reduced leaf necrosis and TMV-coat protein levels in systemic leaves. We, therefore, conclude that BzSA, hitherto unknown natural plant product, is a new SAR inducer in plants.

Newly Identified Targets of Aspirin and Its Primary Metabolite, Salicylic Acid

Salicylic acid (SA) is a plant hormone, which influences several physiological processes, and is a critical modulator of multiple levels of immunity in plants. Several high-throughput screens, which were developed to identify SA-binding proteins through which SA mediates its many physiological effects in plants, uncovered several novel targets of aspirin and its primary metabolite, SA, in humans. These include glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and high mobility group box 1 (HMGB1), two proteins associated with some of the most prevalent and devastating human diseases. In addition, natural and synthetic SA derivatives were discovered, which are much more potent than SA at inhibiting the disease-associated activities of these targets.

Carboxylate-phenolate tautomerism in 5-[(nitrophenyl)diazenyl]salicylate anions.

Aryldiazenyl derivatives of salicylic acid and their salts are used as dyes. In these structures, the carboxylate groups are engaged in short contacts with the cations and in hydrogen bonds with water molecules, if present. If both O atoms of the carboxylate group take part in such interactions, the negative charge is delocalized over the two atoms. In the absence of hydrogen bonds and contacts with cations, the negative charge is localized on one of the O atoms. In the crystal structures of tetramethylammonium 2-hydroxy-5-[(E)-(4-nitrophenyl)diazenyl]benzoate and tetramethylammonium 2-hydroxy-5-[(E)-(2-nitrophenyl)diazenyl]benzoate, both C4H12N(+)·C13H8N3O5(-), all the interactions between the cations and anions are weak, and their effect on the geometry of the anions is negligible. Under these conditions, the 2-nitro-substituted anion is an almost pure phenol-carboxylate tautomer, whereas in the 4-nitro-substituted anion, the phenolic H atom is shifted towards the carboxylate group, and thus the structure of this anion is intermediate between the phenol-carboxylate and phenolate-carboxylic acid tautomeric forms. The probable formation of such an intermediate form is supported by quantum chemical calculations. Being the characteristic feature of this form, a short distance between the phenolic and carboxylate O atoms is observed in the 4-nitro-substituted anion, as well as in the structures of some 3,5-dinitrosalicylates reported in the literature.

Salicylic Acid Derivatives and Other Components from Gaultheria trichoclada

Salicylic Acid Derivatives and Other Components from Gaultheria trichoclada