Siddha Medicine is a valuable therapeutic choice which is classically used for treating viral respiratory infections, this principle of medicine is proven to contain antiviral compounds.
The study is ...aimed to execute the In Silico computational studies of phytoconstituents of Siddha official formulation Kabasura Kudineer and novel herbal preparation - JACOM which are commonly used in treating viral fever and respiratory infectious diseases and could be affective against the ongoing pandemic novel corona virus disease SARS-CoV-2.
Cresset Flare software was used for molecular docking studies against the spike protein SARS-CoV-2 (PDB ID: 6VSB). Further, we also conducted insilico prediction studies on the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates by using online pkCSM and SwissADME web servers.
Totally 37 compounds were screened, of these 9 compounds showed high binding affinity against SARS-CoV-2 spike protein. All the phytoconstituents were free from carcinogenic and tumorigenic properties. Based on these, we proposed the new formulation called as “SNACK–V”
Based on further experiments and clinical trials, these formulations could be used for effective treatment of COVID-19.
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•In silico Docking Studies of Kabasura Kudineer-Official Siddha Formulation and JACOM against SARS-CoV-2 spike protein.•37 Phytochemical constituents were docked to spike glycoprotein of SARS-COV-2 (PDB ID: 6VSB) by using Cresset Flare software.•Chrysoeriol and Luteolin from Kabasura Kudineer and Quercetin from JACOM shown the highest dock score values of above -11.00.•In silico ADME and drug Likeliness and synthetic accessibility were also carried out for phytoconstituents.
In India as well as globally, diabetes is in a state of high risk and next to cardiovascular disease. As per the WHO, the risk of diabetes is expected to rise about 511 million by 2030. In quest of ...novel targets for type-2 diabetes, many targets were elucidated, such as Glycogen Synthase Kinase-3 (GSK-3), Dipeptidyl Peptidase (DPP-IV), PPAR-γ, α-Glucosidase, α-Amylase, GLP-1, and SGLT. Among the targets, GSK-3 was reported to be an effective target for the treatment of diabetes. In the metabolism of glycogen, GSK is a regulatory enzyme for the biosynthesis of glycogen (glycogenesis). It catalyzes the synthesis of a linear unbranched molecule with 1,4-α-glycosidic linkages. GSK-3 family has two isoenzymes, namely α and β, which differ in their Nand C- terminal sequences and are semi-conservative multifunctional serine/threonine kinase enzymes. In this chapter, we discuss an overview of general diabetic mechanisms and how GSK-3 modulation may influence these processes. Mutation in the GSK-3 complex causes diabetes. Synthetic and natural scaffolds modulate GSK-3 against diabetes and leading to its optimization for the development of GSK-3 inhibitors. This review mainly focuses on the development of GSK-3 inhibitors and highlights current and potential future therapeutic approaches that support the notion of targeting glucose metabolism with novel antidiabetic agents.
A series of amide derivatives of azaindole-oxazoles (11a-n) were designed and synthesized and their structures were confirmed by
1
HNMR,
13
CNMR and mass spectral analysis. Further, these derivatives ...were screened for their anticancer activity against human cancer cell lines viz; MCF7 (breast), A549 (lung) and A375 (melanoma). In vitro anticancer activity screening indicated that most of the hybrids exhibited potent inhibitory activities in a variety of cancer cell lines. Among the compounds 11d, 11e, 11f, 11j, 11k, 11l, 11m, and 11n were exhibited more potent activity than standard, in those mainly two compounds 11m and 11j were exhibited excellent activity in MCF-7 cell line with IC
50
values 0.034 and 0.036 µM. Moreover, all these compounds were carried out their molecular docking studies on EGFR receptor results indicated that two potent compounds 11m and 11j were strongly binds to protein EGFR (PDB ID: 4hjo). It was found that the energy calculations were in good agreement with the observed IC
50
values.
A series of new β-isatin aldehyde-
N
,
N
′-thiocarbohydrazone, bis-β-isatin thiocarbohydrazones, bis-β-isatin carbohydrazones was synthesized by condensation of 5-substituted isatin with ...thiocarbohydrazide or carbohydrazide. The chemical structures of the newly synthesized compounds were confirmed by FT-IR,
1
H NMR, and mass spectral analysis. The synthesized compounds were evaluated for in vitro antiviral activity against various strains of DNA and RNA viruses, but exhibited moderate antiviral activity compared with the reference compounds. Among all the compounds
6c
exhibited the highest chemoprevention activity in a two-stage mouse-skin carcinogenesis test.
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A series of novel 3-(substituted)-2-(substituted quinazolinylamino)quinazolin-4(3H)-ones were synthesized by the reaction of 3-(substituted)-2-hydrazino-quinazoline-4(3H)-ones with ...2-phenyl-3,1-benzoxazin-4-one. The starting materials 3-(substituted)-2-hydrazino-quinazolin-4(3H)-ones were synthesized from various primary amines by a multistep synthesis. All the title compounds were tested for their antibacterial activity using ciprofloxacin as reference standard. Compounds 3-(4-fluorophenyl)-2-(4-oxo-2-phenylquinazolin-3(4H)-ylamino)quinazolin-4(3H)-one (9a) and 3-(4-chlorophenyl)-2-(4-oxo-2-phenylquinazolin-3(4H)-ylamino)quinazolin-4(3H)-one (9h) emerged as the most active compounds of the series. These compounds have shown most potent antibacterial activity against the tested organisms of Proteus vulgaris and Bacillus subtilis having zone of inhibition values of 1.1 cm and 1.4 cm for compound 9a 1.2 cm and 1.0 cm for compound 9h, respectively.
The present work aimed to develop a Field-based 3D-QSAR model with existing JAK-2 inhibitors. The JAK-STAT pathway is known to play a role in the development of autoimmune diseases, including ...rheumatoid arthritis, ulcerative colitis, and Crohn's disease. Dysregulation of JAK-STAT is also linked to the development of myelofibrosis and other myeloproliferative diseases. JAK antagonists can be used in many areas of medicine. There are many compounds that already show inhibition of Jak-2. We have developed a Field-based 3D QSAR model which showed good correlation values (r
2
0.884 and q
2
0.67) with an external test set regression pred_r
2
0.562. Various properties, such as electronegativity, electro positivity, hydrophobicity, and shape features, were studied under the activity atlas to determine the inhibitory potential of ligands. These were also identified as important structural features responsible for biological activity. We performed virtual screening based on the pharmacophore features of the co-crystal ligand (PDB ID: 3KRR) and a dataset of NPS was selected with a RMSD value less than 0.8. The developed 3D QSAR model was used to screen ligands and calculate the predicted JAK-2 inhibition activity (pKi). The results of the virtual screening were validated using molecular docking and molecular dynamics simulations. SNP1 (SN00154718) and SNP2 (SN00213825) showed binding affinity of −11.16 and −11.08 kcal/mol, respectively, which were very close to the crystal ligand of 3KRR, −11.67 kcal/mol. The RMSD plot of the protein-ligand complex of SNP1 and 3KRR showed stable interactions with an average RMSD of 2.89 Å. Thus, a statistically robust 3D QSAR model could reveal more inhibitors and aid in the design of novel JAK-2 inhibitors.
A new library of structurally modified aryl quinazoline-isoxazole (12a-j) derivatives have been designed, synthesized and characterized by
1
HNMR,
13
CNMR and mass spectral data. Further these ...compounds were evaluated for anticancer applications against four human cancer cell lines including PC3, DU-145 (prostate cancer), A549 (lung cancer) and MCF-7 (breast cancer) by utilizing the MTT assay. The results were compared with etoposide which was used as positive control. Most of the compounds showed good to moderate anticancer activities against the four cancer cell lines. Among them, compounds 12a, 12b, 12c, 12d and 12j exhibited more potent activities. Further, molecular docking studies were carried out for all synthesized compounds against the cancer targets Selective Human Androgen Receptor (PDB ID: 3V49) and Abl-Tyrosine kinase (PDB ID: 1IEP). All the docked ligands have exhibited good binding interactions with the targeted protein.
A simple, selective and rapid ultra performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous estimation of dolutegravir, lamivudine and ...tenofovir in bulk and tablet dosage form. Chromatographic separation was attained on Acquity Ethylene Bridged Hybrid (BEH) C18 column (50 × 2.1 mm, 3.5 µm), using a mixture of acetonitrile and 0.1% formic acid in water (60:40, v/v) as a mobile phase at a flow rate of 0.12 mL/min. The total run time of analysis was 3.5 min. The analytes were detected using tandem mass spectrometry, operating in positive ionization and multiple reaction monitoring modes. The method's linearity was determined to be in the range of 10–150 ng/mL with r2 > 0.99. The proposed method was validated as per the International Council for Harmonization (ICH) guidelines, and the results were found well within the acceptance limits. The method was successfully applied for the simultaneous quantification of all the three analytes in the combined tablet dosage form.
•Series of novel thizolyl-benzimidazole derivatives were synthesized using PEG-400 solvent via MCR approach.•These are evaluated for in-vitro anti-diabetic activity screening with Acarbose.•Among the ...tested compounds, compound 4d, 4c, 4 h, 4j and 4b have shown significant anti-diabetic activity.•The IC50 values 12.02 ± 0.56; 12.25± 0.28; 12.74 ± 0.45; 17.83 ± 0.21 and 19.10 ± 0.88 μg/mL respectively.•Molecular docking studies revealed compounds 4c and 4d to have stable binding patterns to the human pancreatic α–amylase (PDB ID: 4W93) with Trp43, Tyr59, Tyr62, His305, and Asp356 amino acid residues.•In-silico ADME analysis: all compounds follow the Lipinski's rule of 5.
Polyethylene glycol promoted, novel, one-pot, three-component synthesis of benzimidazole based thaizole derivatives (4a-s) has been synthesized via a multi-component approach by using 5-amino-2-mercaptobenzimidazole, phenyl isothiocyanates, and substituted phenacyl bromides using PEG-400 as a recyclable and greener solvent in a shorter reaction time without any by-products. All the synthesized compounds (4a-s) were well characterized by analytical and spectroscopic techniques. Furthermore, some of the synthesized compounds were evaluated for their in-vitro α-amylase inhibition activity using Acarbose as a standard positive control. Among the tested scaffolds, compound 4d, 4c, 4 h, 4j and 4b have shown significant inhibitory activity against α-amylase enzyme with IC50 values 12.02 ± 0.56; 12.25± 0.28; 12.74 ± 0.45; 17.83 ± 0.21 and 19.10 ± 0.88 μg/mL respectively. Also we insight in to the molecular docking studies, based on the binding results, compounds 4c and 4d to have shown stable binding patterns to the human pancreatic α–amylase with montbretin A (PDBID: 4W93). The structure-activity relationship (SAR) studies of all the title scaffolds were also established. The α- amylase inhibition, molecular docking studies, molecular dynamic simulations, and drug-likeness properties (Lipinski parameters and in-silico ADME properties) of the title compounds were suggested that these are promising anti-diabetic active skeletons.
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