Novel Coumarin-Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer's Disease.

In this research, a series of coumarin-based scaffolds linked to pyridine derivatives via a flexible aliphatic linkage were synthesized and assessed as multifunctional anti-AD agents. All the compounds showed acceptable acetylcholinesterase (AChE) inhibition activity in the nanomolar range (IC50 = 2-144 nM) and remarkable butyrylcholinesterase (BuChE) inhibition property (IC50 = 9-123 nM) compared to donepezil as the standard drug (IC50 = 14 and 275 nM, respectively). Compound 3f as the best AChE inhibitor (IC50 = 2 nM) showed acceptable BuChE inhibition activity (IC50 = 24 nM), 100 times more active than the standard drug. Compound 3f could also significantly protect PC12 and SH-SY5Y cells against H2O2-induced cell death and amyloid toxicity, respectively, superior to the standard drugs. It could interestingly reduce ß-amyloid self and AChE-induced aggregation, more potent than the standard drug. All the results suggest that compound 3f could be considered as a promising multi-target-directed ligand (MTDL) against AD.

Efficient synthesis of 1,3-naphtoxazine derivatives using reusable magnetic catalyst (GO-Fe3O4-Ti(IV)): anticonvulsant evaluation and computational studies.

A series of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines (S1-S11) were synthesized with an eco-friendly and recoverable nanocatalyst (GO-Fe3O4-Ti(IV)) as an efficient magnetic composite. The new nanocatalyst was characterized by FT-IR, XRD and, EDS analysis. A conformable procedure, easy to work up and having a short reaction time with high yields are some advantages of this method. The new catalyst is also thermal-stable, reusable and, environment-friendly. The chemical structures of the synthesized 1,3-oxazine compounds were confirmed by comparing their melting points with those reported in literature. Then, the anticonvulsant activity of these compounds was assessed by the intraperitoneal pentylenetetrazole test (ipPTZ). Compounds S10 and S11 displayed considerable activity against chemically-induced seizure tests. The molecular simulation was also done to achieve their binding affinities as γ-aminobutyric acid A (GABA-A) receptor agonists as an assumptive mechanism of their anticonvulsant action. The result of molecular studies represented strongly matched with biological activity. Molecular docking simulation of the potent compound (S10) and diazepam as the positive control was performed and some critical residues like Thr262, Asn265, Met286, Phe289, and Val290 were identified. Based on the anticonvulsant results and also in silico ADME predictions, S11 can be to become a potential drug candidate as an anticonvulsant agent.

Nano-SiO2/DBN: an efficacious and reusable catalyst for one-pot synthesis of tetrahydrobenzo[b]pyran derivatives.

BACKGROUND: The nano-sized particles enhance the exposed surface area of the active part of the catalyst, thereby increasing the contact between precursors and catalyst considerably. In this study, nano-SiO2/1,5-diazabicyclo[4.3.0]non-5-en was synthesized, characterized and used as a heterogeneous nanocatalyst for the synthesis of tetrahydrobenzo[b]pyran derivatives. Fourier Transform Infrared Spectroscopy, Field Emission Scanning Electron Microscopy, Brunauer-Emmett-Teller plot, Energy Dispersive X-ray Spectroscopy and Thermo Gravimetric Analysis were used to discern nano-SiO2/1,5-diazabicyclo[4.3.0]non-5-en. RESULTS: Tetrahydrobenzo[b]pyrans were synthesized by using nano-SiO2/1,5-diazabicyclo[4.3.0]non-5-en via one-pot three-component condensation of malononitrile, aldehydes and dimedone in H2O/EtOH at 60 °C. The results indicate that tetrahydrobenzo[b]pyrans were synthesized in good to high yields and short reaction times. CONCLUSIONS: The fundamental privileges of this method are short reaction time, plain procedure, recyclability of catalyst and high yields of products.

A review on flavonoid-based scaffolds as multi-target-directed ligands (MTDLs) for Alzheimer's disease.

Alzheimer's disease (AD), the most common form of dementia, is a multifactorial neurodegenerative disease. The target enzymes inhibition including cholinesterase, beta-secretase, monoamine oxidase and inhibition of amyloid-ß aggregation as well as oxidative stress and metal chelation play an important role in the pathogenesis of AD. Chroman-4-one scaffold with benzo-γ-pyrone network is a privileged structure in organic synthesis and drug design. A large number of research has been carried out on modified naturally occurring chromanone scaffolds and/or synthesized new analogues, to obtain effective drugs for AD management. The present review summarizes aspects related to the multi-target-directed ligands (MTDLs) strategy in enzyme targets modulation performed with natural and synthesized chroman-4-one-based structures to look at their potential in the management of multifactorial Alzheimer's disease.

Comparing the effects of reflexology methods and Ibuprofen administration on dysmenorrhea in female students of Isfahan University of Medical Sciences.

BACKGROUND: Dysmenorrhea or menstrual pain is one of the most common disorders experienced by 50% of women in their reproductive age. Adverse effects of medical treatments and its failure rate of 20-25% have caused many women to seek other complementary and alternative treatment methods for primary dysmenorrhea. Hence, this study aimed to compare and determine the efficacy of reflexology and Ibuprofen on reduction of pain intensity and duration of menstrual pain. METHODS: This was a quasi-experimental clinical trial study on 68 students with primary dysmenorrhea living in Isfahan University of Medical Sciences' dormitories. Simple random sampling was done considering the inclusion criteria and then the students were randomly divided into two groups. In the reflexology group, the subjects received 10 reflexology sessions (40 minutes each) in two consecutive mense cycles. The Ibuprofen group received Ibuprofen (400 mg), once every eight hours for 3 days during 3 consecutive mense cycles. To assess the severity of dysmenorrhea, Standard McGill Pain Questionnaire, visual analog scale (VAS) and pain rating index (PRI) were used in this study. RESULTS: Findings of the study showed that the two groups had no statistically significant difference in terms of demographic characteristics (p > 0.05). Reflexology method was associated with more reduction of intensity and duration of menstrual pain in comparison with Ibuprofen therapy. Independent and Paired t-test showed that there was a significant difference in the two groups between intensity and duration of menstrual pain using VAS and PRI in each of the 3 cycles between reflexology and Ibuprofen groups (p < 0.05). CONCLUSIONS: Considering the results of the study, reflexology was superior to Ibuprofen on reducing dysmenorrhea and its treatment effect continued even after discontinuing the intervention in the third cycle. Therefore, considering that reflexology is a non-invasive, easy and cheap technique, it seems that it can replace anti-inflammatory drugs (NSAIDs) to avoid their adverse side effects.