Current Organic Chemistry - Volume 22, Issue 17, 2018

Background: Histamine is a chemical transmitter widely distributed in the human body. It exerts its effects through the interaction with histaminergic receptors (H1R to H4R). The H4R is mainly expressed in hematopoietic cells, especially those involved in immune and inflammatory responses, and thus it is an important target for novel antiinflammatory agents for the treatment of disorders such as asthma, dermatitis, rheumatoid arthritis, peritonitis, inflammatory bowel disease and allergic rhinitis. Current pharmacological therapy for the treatment of such inflammatory disorders includes poorly effective drugs in many cases, also causing important adverse reactions. Accordingly, the development of new drugs has been widely explored, especially those with a different mechanism of action from NSAIDs and corticosteroids. Discussion: H4R antagonists/inverse agonists have demonstrated potential anti-inflammatory properties and thus several ligands have been reported, showing efficacy in several clinical and preclinical studies. The indolcarboxamides, aminopyrimidines, quinoxalines and quinazolines have been the most critically explored scaffolds to achieve highly selective and potent antagonists/inverse agonists. These derivatives have shown in vivo activity and important contributions for the structure-activity relationship data. Conclusion: In this paper, a review of the main ligands is undertaken and reported in the literature showing in vivo anti-inflammatory activity and potential therapeutic application.

The inflammatory process is both natural and endogenous, occurring as a response of the organism to infectious or irritant agents. Although it is an organic response to an aggressor, and should be considered beneficial, it is not. Inflammation causes pain, edema, increased temperature, and often results in decreased mobility and quality of life for the patient. Chronic disturbances such as bowel, autoimmune diseases and asthma are all examples where an inflammatory response develops. Methods involving theoretical chemistry are widely diffused both in academia and industry because of their ability to considerably reduce both time and costs in new drug discovery endeavors. They can provide useful information concerning the steric and lipophilic nature of probable drug to biological target interactions as well as establishing quantitative relationships between chemical structures and biological activity for a series of investigated compounds. Such methods assist our understanding of mechanisms of action responsible for the known biological effect, describing and explaining experimental results; where one can essentially test for outcomes before realizing bench experiments. Based on the above, this review reported in silico studies between 2007-2017 and aims to investigate how methods involving theoretical chemistry contribute to the development of new drugs which present more efficient antiinflammatory activities with fewer side effects.

The therapeutic potential of some Linum species has been reported previously. Nonetheless, several species of this genus warrant further scientific consideration. In this study, the phenolic composition, antioxidant activity (DPPH, phosphomolybdenum, iron chelating, hydroxyl radical and lipid peroxidation assays) and cytotoxicity effect (human rhabdomyosarcoma, human cervix carcinoma, and murine fibroblast cell lines) of ethyl acetate, methanol, and water extracts of three Linum species (Linum austriacum subsp. glaucescens, Linum hirsutum subsp. anatolicum, and Linum tenuifolium) were assessed. High performance liquid chromatography with diode-array detection (HPLC-DAD) analysis revealed the presence of ferulic acid, p-hydroxybenzoic acid, synapic acid, rutin, apigenin-glucoside, quercetin, luteolin, and naringenin in all the extracts. It was observed that the extracts (IC50 ranging from 42.07 to 51.66 μg/mL) showed IC50 significantly (p<0.05) lower than ascorbic and gallic acid (> 1000 and 255.43 μg/mL respectively) against lipid peroxidation. According to the American National Cancer Institute guidelines, the extracts showed low cytotoxicity (IC50 < 30 μg/mL). However, the water extracts showed cytotoxicity effects (IC50 17.43±0.13 to 28.12±0.66 μg/mL) against the studied cell lines as compared to the antineoplastic positive control (Cis-DDP). These findings support the use of these plants in the management of ROS mediated disorders and advocates for the need for further scientific evaluations to confirm the observed in vitro bioactivity. The cytotoxic potential coupled with the antioxidant property of the water extracts of these plant species is of particular interest which can open new avenues in the quest for novel anticancer drugs.

Adiantum capillus-veneris L. is one of the best ferns that are used in traditional medicine for breaking kidney stones. This study aimed to evaluate antioxidant activity of the different extracts of A. capillus-veneris using the phosphomolybdenum assay, free radical scavenging activity (DPPH), ferric reducing antioxidant power (FRAP), and cupric ion reducing power activity test (CUPRAC). Besides, the enzyme inhibition activities were determined against acetylcholinesterase, tyrosinase, α-glucosidase and α-amylase. Total and individual phenolic compounds were also determined by spectrophotometric and HPLC methods, respectively. Total phenolic and flavonoid contents were found to change between 354-441 mg GAE/g and 23-123 mg QE/g, respectively. The major phenolic compounds were benzoic acid, epicatechin, syringic acid and catechin. Methanol and ethyl acetate extracts exhibited stronger antioxidant abilities compared to water extract. A. capillus-veneris extracts showed high enzyme inhibition activities except for butrylcholinesterase. The results indicated that the different extracts of A. capillus-veneris L. can be used as natural sources of antioxidants and enzyme inhibitors.

Considering highly important biological and medicinal properties of chromenes, synthesis of these heterocycles has attracted the interest of medicinal and organic chemists. This review includes the recent investigation in the multicomponent synthesis of chromene systems and describes the literature reports for the period of 2000 to early 2018. These reported strategies carried out in the classical and non-classical conditions particularly under a green condition such as using green solvents, catalyst and solvent-free conditions.