Sung-Yum Seo

Antidiabetic and antiacetylcholinesterase effects of ethyl acetate fraction of Chaenomeles sinensis (Thouin) Koehne fruits in streptozotocin-induced diabetic rats.

The present study was intended to examine the effects of the supplementation of active α-glucosidase, α-amylase and lipase inhibitory ethyl acetate (CSE) fraction from the fruits of Chaenomeles sinensis (Thouin) Koehne on blood glucose (BG), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransaminase (AST), acetylcholinesterase (AChE) and antioxidant levels. The diabetic rats were treated orally with CSE at the doses of 50 and 100 mg/kg bw for 14 days. BG, TC, TG, HDL-C, ALT, AST and AChE levels were significantly reduced; on the other hand antioxidant levels were significantly increased in the treated groups. These observations suggest protective effects of CSE against STZ-induced diabetic dementia model.

Design, synthesis and bioevaluation of novel umbelliferone analogues as potential mushroom tyrosinase inhibitors

Abstract A series of umbelliferone analogues were synthesized and their inhibitory effects on the DPPH and mushroom tyrosinase were evaluated. The results showed that some of the synthesized compounds exhibited significant mushroom tyrosinase inhibitory activities. Especially, 2-oxo-2-[(2-oxo-2H-chromen-7-yl)oxy]ethyl-2,4-dihydroxybenzoate (4e) bearing 2,4-dihydroxy substituted phenyl ring exhibited the most potent tyrosinase inhibitory activity with IC50 value 8.96 µM and IC50 value of kojic acid is 16.69. The inhibition mechanism analyzed by Lineweaver–Burk plots revealed that the type of inhibition of compound 4e on tyrosinase was non-competitive. The docking study against tyrosinase enzyme was also performed to determine the binding affinity of the compounds. The compounds 4c and 4e showed the highest binding affinity with active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that compounds 4c and 4e may serve as a structural template for the design and development of novel tyrosinase inhibitors.

Iminothiazoline-Sulfonamide Hybrids as Jack Bean Urease Inhibitors; Synthesis, Kinetic Mechanism and Computational Molecular Modeling

The present work reports the synthesis of several 2‐iminothiazoline derivatives of sulfanilamide (3a–j) as inhibitors of jack bean ureases. The title compounds were synthesized by the heterocyclization of sulfanilamide thioureas with propragyl bromide in dry ethanol in the presence of 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene as a base. All of the compounds showed higher urease inhibitory activity than the standard thiourea. The compounds (3h) and (3i) exhibited excellent enzyme inhibitory activity with IC50 0.064 and 0.058 μm, respectively, while IC50 of thiourea is 20.9 μm. The kinetic mechanism analyzed by Dixon plot showed that compound (3h) is a mixed‐type inhibitor while (3i) is a competitive one. Docking studies suggested that Asp633, Ala636, His492, Ala440, Lue523, Asp494 and Arg439 are the major interacting residues in the binding site of the protein and may have an instrumental role in the inhibition of enzymes function. 2‐iminothiazoline analogues (3a–j) showed good docking score (−10.6466 to −8.7215 Kcal/mol) and binding energy (London dG ranging from −14.4825 to −10.4087 Kcal/mol) which is far better than the standard thiourea (binding score in S field −4.5790 Kcal/mol London dG −4.7726 Kcal/mol). Our results inferred compound (3i) may serve as a structural model for the design of most potent urease inhibitors.

Influence of plasma-activated compounds on melanogenesis and tyrosinase activity

Many organic chemists around the world synthesize medicinal compounds or extract multiple compounds from plants in order to increase the activity and quality of medicines. In this work, we synthesized new eugenol derivatives (ED) and then treated them with an N2 feeding gas atmospheric pressure plasma jet (APPJ) to increase their utility. We studied the tyrosinase-inhibition activity (activity test) and structural changes (circular dichroism) of tyrosinase with ED and plasma activated eugenol derivatives (PAED) in a cell-free environment. Later, we used docking studies to determine the possible interaction sites of ED and PAED compounds with tyrosinase enzyme. Moreover, we studied the possible effect of ED and PAED on melanin synthesis and its mechanism in melanoma (B16F10) cells. Additionally, we investigated the structural changes that occurred in activated ED after plasma treatment using nuclear magnetic resonance (NMR). Hence, this study provides a new perspective on PAED for the field of plasma medicine.

Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking

The current research article reports the synthesis of coumarinyl pyrazolinyl thioamide derivatives and their biological activity as inhibitors of jack bean urease. The coumarinyl pyrazolinyl thioamides were synthesized by reacting thiosemicarbazide with newly synthesized chalcones to afford the products in good yields and the synthesized compounds were purified by recrystallization. Coumarinyl pyrazolinyl thioamide derivatives 5a – 5q showed significant activity against Urease enzyme and also exhibited good antioxidant potential. The compound 3‐(2‐oxo‐2H‐chromen‐3‐yl)‐5‐phenyl‐4,5‐dihydro‐1H‐pyrazole‐1‐carbothioamide (5n) was found to be superior agent in the series with an IC50 = 0.358 ± 0.017 μm compared to standard thiourea with an IC50 = 4720 ± 174 μm. To undermine the binding mode of inhibition kinetic studies were performed for most potent derivative and it was found that compound 5n inhibits urease enzyme by non‐competitive mode of inhibition. Molecular docking studies were carried out to delineate the binding affinity of the synthesized derivatives.

Ameliorative effects of 7-methylcoumarin and 7-methoxycoumarin against CCl4-induced hepatotoxicity in rats

The available conventional remedies for the treatment of drug-induced liver diseases are highly inadequate and possess serious adverse effects; therefore, the development of new, effective drugs is considered necessary. This article explores the hepatoprotective and antioxidant potential of 7-methylcoumarin (MC) and 7-methoxycoumarin (MOC) in CCl4-induced hepatotoxicity in rats. MC and MOC individually, at doses of 50 and 100 mg/kg body weight, were administered orally once-daily for 7 days. The hepatoprotective activity was assessed using various biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin (TB), total protein (TP), and albumin (TA). Serum antioxidant enzyme [e.g., superoxide dismutase (SOD) and catalase (CAT)] levels were determined. Also, thiobarbituric-acid–related substances (TBARS) levels, along with histopathological studies of liver tissue, were scrutinized. Pretreatment with MC and MOC significantly decreased ALT, AST, and TB in the serum of CCl4-induced liver damaged rats in a dose-dependent manner. TA and TP levels in the serum were also restored significantly in all presupplemented MC and MOC groups. In addition, oxidative stress induced by CCl4 was prevented significantly; thereby, increasing SOD and CAT levels and decreasing TBARS levels in liver homogenates. Histopathological studies revealed the ameliorative natures of both the compounds. This study demonstrates the strong hepatoprotective activity of MC and MOC, which could be attributed to their potent antioxidant effects.

Isolation, characterization, and in silico, in vitro and in vivo antiulcer studies of isoimperatorin crystallized from Ostericum koreanum

Abstract Context: Ostericum koreanum (Maxim.) Kitagawa (Apiaceae) roots are traditionally used as an analgesic and antiulcer agent. However, the antiulcer potential of isoimperatorin isolated from O. koreanum has not yet been explored. Aim: To evaluate the antiulcer activity of isoimperatorin isolated from the roots of O. koreanum. Materials and methods: Isoimperatorin was isolated as cubic crystals by repeated column chromatography of the ethyl acetate fraction and structure was verified with 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS-FAB). The crystals obtained were analyzed with the single crystal X-ray method. The MTT assay was used to determine its cytotoxicity against chondrocytes at different concentrations (0.0–737.74 μM, 24 h). The in vivo antiulcer activity of isoimperatorin (40 mg/kg) was determined against ethanol-, indomethacin- and pyloric ligation-induced ulcers in Sprague-Dawley rats. Furthermore, the effect of isoimperatorin (0.0–737.74 μM, 24 h) on the expression of type II collagen in chondrocytes was determined using western blot method. The in vitro urease inhibitory activity of isoimperatorin (0–80 μM) and molecular docking was also performed against urease. Results and discussion: Isoimperatorin demonstrated significant inhibitory activity (IC50 36.43 μM) against urease as compared to the standard drug thiourea (IC50 33.57 μM) without cytotoxic effects. It provided 70.9%, 67.65% and 54.25% protection in ulcer models induced by ethanol, indomethacin and pyloric ligation, respectively. Isoimperatorin showed the highest expression level of type II collagen at 368.87 μM. The docking results confirmed strong binding affinity with the target protein. Conclusion: Isoimperatorin may be used to develop antiulcer drugs with decreased side effects.

Sulfonamide-Linked Ciprofloxacin, Sulfadiazine and Amantadine Derivatives as a Novel Class of Inhibitors of Jack Bean Urease; Synthesis, Kinetic Mechanism and Molecular Docking

Sulfonamide derivatives serve as an important building blocks in the drug design discovery and development (4D) process. Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were also examined. All 24 synthesized compounds exhibited excellent potential against urease enzyme. Compound 3e (IC50 = 0.081 ± 0.003 µM), 6a (IC50 = 0.0022 ± 0.0002 µM), 9e (IC50 = 0.0250 ± 0.0007 µM) and 12d (IC50 = 0.0266 ± 0.0021 µM) were found to be the lead compounds compared to standard (thiourea, IC50 = 17.814 ± 0.096 µM). Molecular docking studies were performed to delineate the binding affinity of the molecules and a kinetic mechanism of enzyme inhibition was propounded. Compounds 3e, 6a and 12d exhibited a mixed type of inhibition, while derivative 9e revealed a non-competitive mode of inhibition. Compounds 12a, 12b, 12d, 12e and 12f showed excellent radical scavenging potency in comparison to the reference drug vitamin C.

Jack Bean Urease Inhibitors, and Antioxidant Activity Based on Palmitic acid Derived 1-acyl-3- Arylthioureas: Synthesis, Kinetic Mechanism and Molecular Docking Studies

A series of acylthioureas was synthesized and their inhibitory effects on the DPPH and jack bean urease were evaluated. The results showed that all of the synthesized compounds exhibited significant jack bean urease inhibitory activities. Especially, 1-(4-chlorophenyl)-3 palmitoylthiourea 5a bearing 4-chloro substituted phenyl ring exhibited the most potent tyrosinase inhibitory activity with an IC50 value 0.0170 μM compared to the IC50 value of 4.720 μM of thiourea used as standard. The inhibition mechanism analyzed by Lineweaver-Burk plots revealed that the type of inhibition of compound 5a on tyrosinase was noncompetitive. The docking study against jack bean urease enzyme was also performed to determine the binding affinity of the compounds. The compounds 4c and 4e showed the highest binding affinity with the active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that all compounds and particularly 5a may serve as a structural template for the design and development of novel urease inhibitors Graphical Abstract.

Evaluation of antidiabetic, antihyperlipidemic and antioxidant effects of Boehmeria nivea (L.) Gaudich., Urticaceae, root extract in streptozotocin-induced diabetic rats

The potential role of 80% methanolic extract of Boehmeria nivea (L.) Gaudich., Urticaceae, root in the treatment of diabetes, along with its antihyperlipidemic and antioxidant effects, was studied in streptozotocin-induced diabetic male Wistar rats. Preliminary screening of the extract revealed the presence of polyphenolics and flavonoids. The animal study was conducted with variable doses of 125, 250 and 500 mg/kg of extract for 21 days in diabetic rats. A significant effect was observed at a dose of 500 mg/kg, which was comparable to the standard drug, glibenclamide. Administration of the extract at a 500 mg/kg dose resulted in a significant reduction of fasting blood glucose, total cholesterol, triglycerides, blood urea, alanine aminotransferase, aspartate aminotransferase, urine sugar and urine ketone levels in diabetic rats in comparison with the diabetic control group. Additionally, this dose significantly increased body weight, hemoglobin, plasma total protein, high density lipoprotein cholesterol, liver glycogen content, superoxide dismutase, reduced glutathione and catalase levels in diabetic rats at the end of 21 days of treatment. Therefore, dietary supplementation with Boehmeria nivea root extract could be beneficial for correcting hyperglycemia, hyperlipidemia and enhancing the antioxidant defense system.