Molecular docking studies of coumarin hybrids as potential acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A/B and ß-amyloid inhibitors for Alzheimer's disease.

Coumarins are the phytochemicals, which belong to the family of benzopyrone, that display interesting pharmacological properties. Several natural, synthetic and semisynthetic coumarin derivatives have been discovered in decades for their applicability as lead structures as drugs. Coumarin based conjugates have been described as potential AChE, BuChE, MAO and ß-amyloid inhibitors. Therefore, the objective of this review is to focus on the construction of these pharmacologically important coumarin analogues with anti-Alzheimer's activities, highlight their docking studies and structure-activity relationships based on their substitution pattern with respect to the selected positions on the chromen ring by emphasising on the research reports conducted in between year 1968 to 2017.

Enzymatic synthesis of polyphenol glycosides catalyzed by transglycosylation reaction of cyclodextrin glucanotransferase derived from Trichoderma viride.

Present study was conducted to evaluate the ability of Trichoderma viride as a source of cyclodextrin glucanotransferase that has shown transglycosylation activity in the presence of polyphenolic constituents extracted from Moringa oleifera leaves as its acceptor and wheat flour as its substrate to catalyze synthesis of polyphenolic glycosides as transglycosylation (transfer) reaction products. The enzymatic synthesized polyphenolic glycosides were then purified using octa-dodecyl-functionalized silica gel column chromatography prior to analysis using thin layer chromatography and high performance liquid chromatography and identified using nuclear magnetic resonance (NMR) spectroscopy. The high performance liquid chromatogram performed that the isolated transglycosylation products had retention times and concentration at 1.446 min (0.0017 mg/ml), 1.431 min (0.14 mg/ml), and 1.474 min (0.012 mg/ml), respectively, compared to the retention time of arbutin (1.474 min) that was applied as authentic standard for polyphenol glycoside. Moreover, observation using 1H NMR as well as 13C NMR showed that structures of the transglycosylation products were identified as gallic acid-4-O-ß-glucopyranoside, ellagicacid-4-O-ß-glucopyranoside, and catechin-4'-O-glucopyranoside, respectively.

4-Thiazolidinone coumarin derivatives as two-component NS2B/NS3 DENV flavivirus serine protease inhibitors: synthesis, molecular docking, biological evaluation and structure-activity relationship studies.

A series of novel 4-thiazolidinone inhibitors SKYa-SKYg, containing coumarin as a core structure were synthesized via facile and efficient method. The structures of the synthesized compounds were established by extensive spectroscopic studies (FT IR, 1D NMR, 2D NMR, LC-MS) and elemental analysis. All the synthesized hybrids were further evaluated for their potential as anti-tubercular agents against Mycobacterium tuberculosis H37Rv ATCC 25618, and anti-bacterial agents against Escherichia coli, Enterobacter aerogenes, Salmonella typhi, Streptococcus pneumoniae and Staphylococcus aureus. Interestingly, the hybrids displayed potent bioactivity. However, compounds SKYc, SKYd, and SKYe appeared to be more effective against the tested bacterial strains, among which compound SKYb showed the highest inhibition against all the bacterial strains ranging from 41 to 165 µg/mL, as compared to the standards, streptomycin, kanamycin and vancomycin. Moreover, derivative SKYa was found to be the strongest against M. tuberculosis (83 µg/mL). Additionally, the anti-dengue potential of the coumarin hybrids as two-component NS2B/NS3 DENV flavivirus serine protease inhibitors was calculated using computational molecular docking approach, with reference to the standards 4-hydroxypanduratin, panduratin and ethyl 3-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy)propanoate with DS of - 3.379, - 3.189 and - 3.381, respectively. The docking results revealed that the synthesized hybrids exhibited potent anti-dengue activity among which compounds SKYf, SKYd, SKYc and SKYe were found to be the best ones with docking scores of - 4.014, - 3.964, - 3.905 and - 3.889. In summary, we discovered 4-thiazolidinone coumarin derivatives as a new scaffold that may eventually yield useful compounds in the treatment of bacterial and viral infections.

Dillenia suffruticosa L. Impedes Carbon Tetrachloride-Induced Hepatic Damage by Modulating Oxidative Stress and Inflammatory Markers in Rats.

Dillenia suffruticosa L. (Dilleniaceae) is used in traditional medicine for protection against various diseases. The current study was designed to investigate the bioactive compounds and hepatoprotective potential of methanol leaves extract of D. suffruticosa against carbon tetrachloride (CCl4)-induced hepatic oxidative injury. Sprague Dawley rats were pretreated with methanol extract of D. suffruticosa leaves (200, 300, and 400 mg/kg body weight [bwt]) once daily for 14 days followed by two doses of CCl4 (1.0 mL/kg bwt). After 2 weeks the rats were sacrificed and hepatoprotective analysis was performed. The identified bioactive compounds include phenol (1.39%); benzyl alcohol (2.04%); 2H-pyran-2-one, 4,6-dimethyl (1.19%); phenol, 2,4-bis(1,1-dimethylethyl) (0.83%); dodecanoic acid (0.84%); hexadecanoic acid, methyl ester (2.66%); n-hexadecanoic acid (0.96%); and phytol (2.13%). The administration of D. suffruticosa significantly depleted the elevation of enzymatic levels of alanine transaminase and aspartate transaminase (4% to 59% recovery), reduced the extent of malondialdehyde production (13% to 79% recovery), elevated the level of reduced glutathione (5% to 21% recovery), and increased the activities of antioxidant enzymes (0.43% to 35% recovery). Histopathological analyses by light and electron microscopy revealed that the plant extract protects the liver from the toxic effects of CCl4 and cured lesions such as necrosis and fatty degeneration. It also decreased hepatocyte injuries such as irregular lamellar organization and dilations in endoplasmic reticulum. Immunohistochemical studies indicate the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxyl-2-nonenal (HNE)-modified protein adducts. In addition, the overexpression of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and prostaglandin E2 (PGE2) are reduced. Hence, we find D. suffruticosa to be a good source of bioactive compounds with hepatoprotective effects against CCl4-induced oxidative damage.