Alpha-glucosidase Inhibitory Effects of Flavonoids, Phenolic Acids and Iridoids Isolated From Vinca soneri: In vitro and in silico Perspectives.

Various Vinca species have been traditionally used for their antihypertensive, sedative, and hemostatic properties, as well as for treating diabetes. In this study, some flavonoids, phenolic acids and iridoids were isolated from an endemic Vinca species, Vinca soneri for the first time. α-Glucosidase inhibitory effects of the isolates were tested and kaempferol-3-O-α-rhamnopyranosyl (1→6) ß-galactopyranoside (1) was found to be the most active one with an IC50 value of 285.73 ± 7.35 µM. Enzyme kinetic assay revealed that it inhibited α-glucosidase in competitive manner. Molecular geometry of 1 was predicted and Frontier molecular orbital analysis was performed using Density Functional Theory (DFT) calculations. Molecular docking and MM-GBSA calculations predicted good fit for 1 in the enzyme active site and key interactions with the catalytic residues. As a result, current study identifies 1 as a promising competitive α-glucosidase inhibitor to be developed as a potential antidiabetic drug candidate.

Effective α-glycosidase inhibitors based on polyphenolic benzothiazole heterocycles.

α-Glycosidase inhibition is one of the main approaches to treat Diabetes mellitus. Polyphenolic moieties are known to be responsible for yielding exhibit potent α-glycosidase inhibitory effects. In addition, compounds containing benzothiazole and Schiff base functionalities were previously reported to show α-glycosidase inhibition. In this paper, the synthesis of seven new phloroglucinol-containing benzothiazole Schiff base derivatives through the reaction of 6-substituted-2-aminobenzothiazole compounds with 2,4,6-trihydroxybenzaldehyde using acetic acid as a catalyst was reported. The synthesized compounds were characterized using spectroscopic methods such as FT-IR, 1H NMR, 13C NMR, and elemental analysis. The synthesized compounds were evaluated for their inhibitory effects on α-glycosidase, compounds 3f and 3g were found to show significant inhibitory properties when compared to the positive control. The IC50 values of 3f and 3g were calculated as 24.05 ± 2.28 and 18.51 ± 1.19 µM, respectively. Kinetic studies revealed that compounds 3f and 3g exhibited uncompetitive mode of inhibition against α-glycosidase. Molecular modeling predicted druglikeness for the title compounds and underpinned the importance of phloroglucinol hydroxyls for interacting with the key residues of α-glycosidase.

In vitro and in silico investigation of FDA-approved drugs to be repurposed against Alzheimer's disease.

Alzheimer's disease (AD), one of the main causes of dementia, is a neurodegenerative disorder. Cholinesterase inhibitors are used in the treatment of AD, but prolonged use of these drugs can lead to serious side effects. Drug repurposing is an approach that aims to reveal the effectiveness of drugs in different diseases beyond their clinical uses. In this work, we investigated in vitro and in silico inhibitory effects of 11 different drugs on cholinesterases. The results showed that trimebutine, theophylline, and levamisole had the highest acetylcholinesterase inhibitory actions among the tested drugs, and these drugs inhibited by 68.70 ± 0.46, 53.25 ± 3.40, and 44.03 ± 1.20%, respectively at 1000 µM. In addition, these drugs are bound to acetylcholinesterase via competitive manner. Molecular modeling predicted good fitness in acetylcholinesterase active site for these drugs and possible central nervous system action for trimebutine. All of these results demonstrated that trimebutine was determined to be the drug with the highest potential for use in AD.

Insights into the Biological Activity and Cytotoxic Mechanism of Epimedium pubigerum.

In this work, the phytochemical characterization, biological activity, and cytotoxic mechanism of aerial and rhizome methanol extracts (SME and RME) of Epimedium pubigerum were investigated to demonstrate its potential usage in the treatment of lung cancer. LC-HRMS analysis, total phenolic/flavonoid content assay, DPPH radical scavenging assay, DNA interaction, cytotoxicity, and western blotting were investigated using different methods. Fumaric acid was found to be the most abundant compound in both extracts. SME and RME were cytotoxic on A549 cells concentration-dependently. Also, in vitro scratch assay showed that SME and RME led to a significant anti-migratory effect at 1 mg/mL. Cytochrome c, p53, and caspase 3 expression significantly increased in the presence of RME compared to the control. All of these results claimed that RME might be suggested as a theoretically more effective phytotherapeutic agent for lung cancer compared to the effect seen with the SME.

Azole derivatives inhibit wildtype butyrylcholinesterase and its common mutants.

Azoles, which have been used for antifungal chemotherapy for decades, have recently been of interest for their efficacy against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). There is little known about the potential of azoles against BChE, however there is none regarding their inhibitory effects against mutants of BChE. In the current study, an azole library of 1-aryl-2-(1H-imidazol-1-yl)ethanol/ethanone oxime esters were tested against AChE and BChE, which yielded derivates more potent than the positive control, galantamine, against both isoforms. Kinetic analyses were performed for wildtype and mutant (A328F and A328Y) inhibition for the two most potent BChE inhibitors, pivalic and 3-bezoylpropanoic acid esters of 2-(1H-imidazol-1-yl)-1-(2-naphthyl)ethanol, which were found to have great affinity to the wildtype and mutant BChE types with Ki values as low as 0.173 ± 0.012 µM. The compounds were identified to show linear competitive or mixed type inhibition. Molecular modeling confirmed these kinetic data and provided further insights regarding molecular basis of BChE inhibition by the active derivatives. Thus, current study suggests new azole derivatives with promising cholinesterase inhibitory effects and reveals the first set of information to promote our understanding for the inhibitory behavior of this class against the mutant BChE forms.

Antifungal Azole Derivatives Featuring Naphthalene Prove Potent and Competitive Cholinesterase Inhibitors with Potential CNS Penetration According to the in Vitro and in Silico Studies.

Cholinesterase inhibition is of great importance in the fight against neurodegenerative disorders such as Alzheimer's disease. Azole antifungals have come under the spotlight with recent discoveries that underline the efficacy and potential of miconazole and its derivatives against cholinesterase enzymes. In this study, we evaluated a library of azoles against acetylcholinesterase and butyrylcholinesterase using in vitro and in silico methods to identify potent inhibitors. Low micromolar IC50 values were obtained for imidazole derivatives, which were further tested and found potent competitive cholinesterase inhibitors via enzyme kinetics study. The active derivatives showed negligible toxicity in in vitro cytotoxicity tests. Molecular modeling studies predicted that these derivatives were druglike, could penetrate blood-brain barrier, and tightly bind to cholinesterase active site making key interactions via the imidazole moiety at protonated state. Thus, current study identifies potent and competitive cholinesterase inhibitor azoles with minor toxicity and potential to pass into the central nervous system.

Synthesis and in vitro α-glucosidase and cholinesterases inhibitory actions of water-soluble metallophthalocyanines bearing ({6-[3-(diethylamino)phenoxy]hexyl}oxy groups.

In this paper, we have prepared peripherally tetra-({6-[3-(diethylamino)phenoxy]hexyl}oxy substituted cobalt(II), copper(II), manganese(III) phthalocyanines (3, 4, 5) and their water-soluble derivatives (3a, 4a, 5a). Then, in vitro α-glucosidase and cholinesterases inhibitory actions of the water-soluble 3a, 4a, 5a were examined using spectrophotometric methods. 4a had the highest inhibitory effects among the tested compounds against α-glucosidase due to IC50 values. 4a and 5a had 40 fold higher inhibitory effects than the positive control. For cholinesterases, the compounds showed significant inhibitory actions that of galantamine which was used as a positive control. According to the SI value, 3a inhibited acetylcholinesterase enzyme selectively. In kinetic studies, 4a was a mixed inhibitor for α-glucosidase, 3a was a competitive inhibitor for AChE, and 4a was a mixed inhibitor for BuChE. The therapeutic potential of these compounds has been demonstrated by in vitro studies, but these data should be supported by further studies.

Giant leiomyoma of the esophagus: a case report and review of the literature.

Although leiomyoma is the most common esophageal mesenchymal neoplasm, it is a rare condition. Resection of the tumor is recommended in symptomatic patients, and observation is recommended in asymptomatic patients with small lesions. We discuss herein a patient admitted to our outpatient clinic for dyspepsia in whom a giant annular esophageal leiomyoma was diagnosed. Resection through thoracoabdominal approach is recommended instead of adjuvant treatment in similar sized tumors.

[Pneumatosis intestinalis mimicking free intraabdominal air: a case report]. / Karin içinde serbest hava görünümü veren Pnömatozis intestinalis: Olgu sunumu.

A 47-year-old male patient had undergone endoscopic balloon dilatation six times due to pyloric stenosis however the result was not satisfying. Surgical treatment was considered. Chest X-ray revealed free sub-diaphragmatic air but there were no acute abdomen signs clinically. In abdominal computerized tomography, there were small intestinal loops anterior to the liver and there was gas collection, which can not be differentiated exactly between an extraluminal free air and the one in the bowel wall of adjacent small bowel segments. In the emergency surgery cysts filled with gas in the wall of distal ileal segments were seen. Pneumatosis intestinalis should be kept in mind in the differential diagnosis of free intraabdominal air.

Mesh invasion of the rectum: an unusual late complication of rectal prolapse repair.

Various surgical techniques have been described for repair of rectal prolapse; however, there is no agreement on a standard treatment method. In the Ripstein procedure, the rectum is fixed to the sacrum with a piece of mesh material. We describe the case of a patient who had undergone a Ripstein procedure to address rectal prolapse 6 years before admission to our clinic. His complaints were anal discomfort, abdominal discomfort, and tenesmus of 2 years duration. Rectoscopy and abdominal computed tomography (CT) revealed that the mesh had penetrated the rectal wall and was located within the rectal lumen 7-8 cm from the anal verge. Once the mesh was endoscopically, and the patient's symptoms resolved completely. Various complications of mesh implantation for rectal prolapse repair have been documented, but rectal wall penetration has not been reported to date. This report presents our case of this unusual complication and reviews the relevant literature.