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•A conserved region “QHGTI” in B and T cell epitopes of dengue envelope glycoprotein was predicted.•A reverse pharmacophore mapping approach was used to develop phamacophore ...model.•ChemBridge database of compounds was screen on the basis of developed pharmacophopre model.•The shortlisted compounds were docked and their interactions were explored.•Finally, 14 compounds were reported as promising drug candidates for the treatment of dengue virus infection.
Dengue virus (DENV) has emerged as a rapidly spreading epidemic throughout the tropical and subtropical regions around the globe. No suitable drug has been designed yet to fight against DENV, therefore, the need for safe and effective antiviral drug has become imperative. The envelope protein of DENV is responsible for mediating the fusion process between viral and host membranes. This work reports an in silico approach to target B and T cell epitopes for dengue envelope protein inhibition. A conserved region “QHGTI” in B and T cell epitopes of dengue envelope glycoprotein was confirmed to be valid for targeting by visualizing its interactions with the host cell membrane TIM-1 protein which acts as a receptor for serotype 2 and 3. A reverse pharmacophore mapping approach was used to generate a seven featured pharmacophore model on the basis of predicted epitope. This pharmacophore model as a 3D query was used to virtually screen a chemical compounds dataset “Chembridge”. A total of 1010 compounds mapped on the developed pharmacophore model. These retrieved hits were subjected to filtering via Lipinski’s rule of five, as a result 442 molecules were shortlisted for further assessment using molecular docking. Finally, 14 hits of different structural properties having interactions with the active site residues of dengue envelope glycoprotein were selected as lead candidates. These structurally diverse lead candidates have strong likelihood to act as further starting structures in the development of novel and potential drugs for the treatment of dengue fever.
The aim of the current study was to synthesize new bioactive compounds and evaluate their therapeutic relevance. The chemical structure of compound 7 (methyl 3-O-phospo-α-D-glucopyranuronic acid was ...elucidated by physical and advance spectral technique. Also, this compound was assessed for various in vitro biological screening. The results showed that compound 7 has promising antifungal activity against selected fungal strains. Computational study was also carried out to find antimalarial efficacy of the synthesized compounds. Compounds (2-7) were tested for cytotoxicity by MTT assay, and no considerable cytotoxicity was observed. Molecular docking study was performed to predict the binding modes of new compound (7). The docking results revealed that the compound has strong attraction towards the target protein, as characterized by good bonding networks. On the basis of the acquired results, it can be predicted that compound (7) might show good inhibitory activity against dengue envelope protein.
The Himalayan region supports a wide diversity of flora and fauna; hence it is home to many natural resources. Despite this, the people living here are struggling for essential needs such as food and ...nutrition. However, in Himalayan region, wild plants and their fruits contribute significantly to the livelihood of local people and communities. Several studies recommended that Himalayan wild fruits possess significant biologically active compounds, antioxidants, vitamins and minerals. In addition, the presence of secondary metabolites in these plants gives them a prominent place in traditional medicinal systems. However, detailed investigation of health-promoting effects, chemical composition, and nutraceutical profiling is lacking in the variety of Himalayan wild fruits. Therefore, this review article will explore the information about wild edible fruits, such as health-promoting effects, chemical composition, and nutraceutical profiling in the Himalayan region. In this context, a detailed search was done through different search engines including Scopus, PubMed, Web of Science, Science Direct and Google Scholar. Specific keywords were used to explore available data about Himalayan wild fruits. Several Himalayan wild fruits like Berberis asiatica, Celtis australis, Ficus palmata, Fragaria indica, Morus alba, Myrica esculenta, Phyllanthus emblica, Prunus armeniaca, etc. showed presence of important bioactive compounds responsible for different therapeutic activities such as anti-inflammatory, anti-diabetic, anticancer, cardioprotective, neuroprotective, antimicrobial, etc. These fruits also possess high nutraceutical value. Hence this study presents detailed information about wild edible fruits which will be helpful in future for researchers, food industries, pharmaceutical industries, and several other government and non-government organisations in developing strategies to ensure food security by using these important wild fruits.
•Three compounds were isolated from Heterophragma adenophyllum.•2-hydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione possessed 98.4% phosphodiesterase-1 inhibition at 2 µM.•All the three compounds ...exhibited potent phosphodiesterase-1 inhibition than standard EDTA salt.•Heterophragma adenophyllum can be used for the treatment of vasoconstriction and various.
Heterophragma adenophyllum (Wall. ex G.Don) Seem belong to family Bignoniacea. To find a safe, effective and economical drugs candidate, the screening of chemical constituents for various biological actions is essential. The isolated compounds (1–3), such as, 2-hydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione (1), methyl 1,2-dihydroxy-2-(3-methylbut-2-enyl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylate (2), 2,2-dimethyl-3,4-dihydro-2H-benzogchromene-5,10-dione (3) were characterized with 1H-NMR, 13C-NMR, EI-MS and UV spectroscopy. The pure constituents have shown significant inhibition potential against phosphodiesterase-1 (PDE-1) with percentage inhibition 98.4, 92.4 and 88.4%, respectively. The IC50 value of the compounds was calculated in which all the three compounds have shown potent activity against clinically important enzyme PDE-1 (IC50 = 21.9 ± 1.12 to 112.4 ± 2.08 µM). When these values were compared with standard EDTA (IC50 = 265.5 ± 2.25 µM), then it is concluded that H. adenophyllum can be used for the treatment of vasoconstriction and various inflammatory conditions. Molecular docking was performed to explore the possible role of isolated bioactive compounds into active sites of snake venom and human PDE-1. The data obtained in terms of binding energy values from docking studies of both snake venom and human PDE-I agrees with the experimental PDE-1 inhibition.
Urease inhibition potential of compound (1), guaiane-type sesquiterpene (2), confertin (3) and scopoletin (4) was carried out with high throughout mechanism-based assay. These compounds were isolated ...from Hypochaeris radicata L., an Asteraceae family member. The pure compounds were screened for their urease and carbonic anhydrase inhibitory activities. The ethyl acetate fractions were subjected to column chromatography, which resulted in the isolation and purification of four compounds (1-4). On evaluation, compounds (1-4) exhibited selective activity against urease enzyme with an IC
50
value of 180.11 ± 2.00, 27.18 ± 0.80, 24.12 ± 0.2 and 30.12 ± 1.10 µM respectively. The compounds (1-4) were found to be inactive against carbonic anhydrase enzyme. Thiourea was used as standard inhibitor (21 ± 0.14 µM) of urease enzyme.
Diospyros lotus, also known as date-plum, belongs to the Ebenaceae family and is mostly recognized as a rootstock for D. kaki. Similar classes of naphthoquinones in D. lotus are investigated against ...cancer and inflammation and have antimicrobial, sedative, and analgesic properties. Six chemical constituents (1-6) were isolated from Diospyros lotus and tested for anti-inflammatory effects at the dose of 2.5 and 5 mg/kg, i.p., using carrageenan (1%, 0.05 ml)-induced paw edema. The maximum protection against carrageenan-induced edema was observed for compounds 1 and 2. Both studied compounds demonstrated significant anti-inflammatory effect after the 3rd hour of posttreatment. The maximum anti-inflammatory effect of compound 1 was 85.96%, while that of compound 2 was 81.44%, followed by compounds 5 and 6, which exhibited 80.11% and 82.45% effect, respectively. Similarly, histamine-induced inflammation was significantly antagonized by 1, 2, 5, and 6 with 87.99%, 82.18±1.8, 80.40±1.59, and 77.44% effects, respectively, at 5 mg/kg after the 2nd hour of posttreatment. The rest of the tested compounds did not show any significant effect as compared to the negative control. Interestingly, no toxicity was observed at higher doses. Moreover, the extracted compounds showed remarkable antibacterial activity against the Gram-positive bacteria and no effect against the Gram-negative bacteria. Docking studies on target cyclooxygenases showed that all the compounds established interactions with the key amino acid residues present in the additional pocket of COX-2. Hence, these compounds may act as selective COX-2 inhibitors. In conclusion, the findings of the current study suggest that the roots of Diospyros lotus may contain some anti-inflammatory and antibacterial agents with minimal toxicological effects and accordingly this plant product is recommended for further investigations.
Heterophragma adenophyllum (HA) is an important medicinal plant which is used in traditional medicine for the treatment of muscular tension and pain. Herein, we report the isolation of ...methyl,1,2-dihydroxy-2-(3-methylbut-2-en-1-yl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylate (1), from the roots of H. adenophyllum. The isolated compound 1 was evaluated for in vivo muscle relaxant, sedative, and analgesic potential in Swiss albino mice. Results revealed that the isolated compound 1 exhibited a dose- and time-dependent muscle coordination (51%) and a significant (p < 01) sedative effect. It also showed a considerable (p < 0.5) analgesia after 30 min of post treatment and was maintained for up-to 120 min of experimental duration. In acute toxicity studies, no mortality was observed which indicates a preliminary safety of compound 1. Furthermore, the experimental results were compared with the theoretical studies by using density functional theory (DFT). The stability of the compound as well as the flow of electrons was determined by the calculated Frontier orbital analysis. The calculated stretching frequencies,
1
H-NMR/
13
C-NMR chemical shift values and UV-visible spectra were found to be in agreement with experimental values. The results obtained from molecular docking studies were used to explore the mechanism of analgesic and muscle relaxant activity.
Communicated by Ramaswamy H. Sarma
Graphical abstract Graphical abstract showing the sedative-hypnotic like effect and molecular docking of Di-naphthodiospyrol from Diospyros lotus root extract in animal model.
Computational Study of Pharmacophores: β-Sultams Barwick, Mathew; Abu-Izneid, Tareq; Novak, Igor
The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory,
10/2008, Letnik:
112, Številka:
43
Journal Article
Recenzirano
The strain and resonance energies in β-sultam derivatives have been calculated by using a high-level ab initio method (G3/B3LYP) in order to resolve the question of the principal driving force ...affecting solvolysis of these new antibiotics. We found that only the combined effect of stabilizing (via amide or sulfonamide resonance interactions) and destabilizing (ring strain) influences can account for the observed rates of solvolysis in β-lactams and β-sultams.
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