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Warfarin containing a 4-hydroxycoumarin moiety possesses excellent anticoagulant activity, with the (S) enantiomer being the eutomer. The present work is designed to synthesize warfarin based derivatives enantioselectivity to explore their anticoagulant potential. The substituted chalcones were reacted with 4-hydroxycoumarin in the presence of the chiral organocatalyst 9-amino-9-deoxyepiquinine to afford warfarin-based analogues 5a- 5k. The structures of synthesized compounds 5a-5k were confirmed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy (1H NMR), carbon-13 nuclear magnetic resonance spectroscopy (13C NMR) and electron ionization mass spectroscopy (EIMS) data. The enantiomeric excess (ee) has been found in the range of 16-99% as determined by chiral high-performance liquid chromatography (HPLC) analysis. The in vitroanticoagulant activity of the products 5a-5k was evaluated by plasma recalcification time (PRT) method, and it was found that most of the derivatives showed good anticoagulant activity, specifically compound 5b exhibited excellent results compared to that of warfarin. Compound 5b displayed an IC50value of 249.88 µM, which is better than that of warfarin (IC50408.70 µM). The molecular docking studies have been performed against vitamin K epoxide reductase with PDBID 3kp9. The synthesized compounds bind well in the active binding site of the target enzyme. The derivative 5b showed π-π stacking interactions with the amino acid phenylalanine (Phe 114). The antimicrobial activity of synthesized compounds has also been evaluated, and results showed moderate antimicrobial activity. Based on our results, it is proposed that derivative 5b may act as a lead compound to design more potent anticoagulant derivatives.

In this study, we investigated how electroosmsis, viscous dissipation, and slippage affect the peristaltic flow of complex cilia-generated flow of hybrid nanofluid in a ciliated tube. The complex cilia-generated flow is characterized by a complex sinusoidal wave that transmits along the wall of the tube with a uniform speed having distinct amplitudes. The main objective of this work is to examine how this complex cilia on the wall drives the hybrid nanofluid flow under electroosmosis. The Helmholtz–Smoluchowski equation is used to model the electroosmosis, and the Poisson equation is solved analytically using the Debye-Huckel approximation. The lubrication approach is utilized to simplify the governing equations. The governing non-dimensional equations for hybrid nanofluid are solved exactly using the DSolve command of Mathematica. The results are presented graphically to accomplish the theoretical results from the complex-cilia wave evolution from the necessary flow parameters in an asymmetric tube. The study shows that increasing the electroosmotic parameter leads to an increase in the velocity profile at the boundary and a decrease in the middle of the tube. Conversely, the Helmholtz–Smoluchowski velocity parameter has the opposite effect. The Brinkman parameter increases the temperature of the hybrid nanofluid. The study also presents a graphical analysis of pressure rise and pressure gradient for various values of the parameters. The pressure rise against volumetric flow is rate and pressure gradient increases by increasing the electroosmotic parameter and Helmholtz-Smoluchowski parameter, while it decreases for increasing the velocity slip parameter. The streamlines are drawn to study the trapping phenomena of blood in the hybrid nanofluid flow in an asymmetric tube by the formation of bolus and the division of streamlines. It is observed that the size and number of bolus close to the artery walls increases for electroosmotic parameter while reverse behavior is observed for Helmholtz-Smoluchowski parameter. The tabular presentation of the heat transfer coefficient at the wall is presented. The current results can be used in bio mathematical models to control fluid flow through micro-channels and to investigate ways to cure artery blockages and cancer tumors in biomedicine. The study can also be used to design and optimize microfluidic devices for drug delivery, lab-on-a-chip devices, and other biomedical applications.

Background: Due to the pressing need and adverse effects associated with the available anti-cancer agents, an attempt was made to develop the new anti-cancer agents with better activity and lesser adverse effects. Objective: Synthetic approaches based on chemical modification of quinoline derivatives have been undertaken with the aim of improving anti-cancer agents’ safety profile. Methods: In the present study, quinoline derivatives 6-hydroxy-2-(4-methoxyphenyl) quinoline-4-carboxylic acid (M1) and 2-(4-chlorophenyl)-6-hydroxyquinoline-4-carboxylic acid (M3) were synthesized by the reaction of aldehyde and pyruvic acid. The complete reaction was indicated by thin-layer chromatography. Newly synthesized M1and M3were tested for in silico and in vitro studies. Results: M1 and M3 were docked against selected targets. Both the test compounds showed good affinity against all targets except the p300\CBP-associated factor target as there was no H-bond formed by M1. IC50 values of M1 and M3 against 1, 1-diphenyl-picrylhydrazyl free radical scavenging activity were 562 and 136.56ng/mL, respectively. In brine shrimp lethality assay, M1 and M3 showed IC50 value of 81.98 and 139.2ng/mL, respectively. IC50 values recorded for M1 and M3 in tumor inhibition activity were 129 and 219μg/mL, respectively. M1 and M3 exhibited concentration-dependent anti-cancer effects against human cell lines of hepatocellular carcinoma (HepG2) and colon cancer (HCT-116). Against HepG2 cells, M1 and M3 exhibited IC50 of 88.6 and 43.62μg/mL, respectively. M1 and M3 utilized against HCT-116 cell lines possessed IC50 values of 62.5 and 15.3μg/mL. M1 and M3 also showed an anti-leishmanial effect with IC50 values of 336.64 and 530.142μg/mL, respectively. Conclusion: From the results of pharmacological studies, we conclude that the newly synthesized compound showed enhanced anti-oxidant, anti-cancer and anti-leishmanial profile with good yield.

Background: Diabetes is a chronic endocrine associated metabolic ailment. It is chiefly characterized by hyperglycemia, which results due to deficient insulin levels caused by either obliteration of pancreatic beta cells or the incompetent sensitivity of insulin at the target tissue. Methods: In the present study, selected compounds (Abrotandiol, Abrotanone, Lariciresinol, Pinoresinol, Syringaresinol and Taxiresinol) from Perovskia atriplicifolia were evaluated for antidiabetic potentials using molecular docking simulations and computational tools. Results: All selected compounds possess moderate to strong respective activities against aldose reductase, DPP-IV, PTPB, insulin receptor and PPAR-g. Selected compounds that include Abrotandiol, Lariciresinol, Pinoresinol, Syringaresinol, Abrotanone and Taxiresinol have shown highest binding energies of ΔG = -9.3 kcal/mol, -8.9 kcal/mol, -8.9 kcal/mol, -8.8 kcal/mol, -8.8 kcal/mol and -7.6 kcal/mol respectively against PPAR-g. However, out of six compounds, Abrotanone has shown strong potential binding energy against all selected targets, i.e. ΔG = -7.8 kcal/mol with aldose reductase, ΔG = -10.3 kcal/mol with DPP-IV, ΔG = -9.3 kcal/mol with PTPB and ΔG = -8.3 kcal/mol with insulin receptors. Conclusion: The present study proposed that all selected compounds possess antidiabetic activity. However, Abrotanone has a strong antidiabetic potential. This assumption provides better insight to evaluate further these compounds for in vitro and in vivo testing against diabetes in future.

Background: Diabetes is a chronic endocrine associated metabolic ailment. It is chiefly characterized by hyperglycemia, which results due to deficient insulin levels caused by either obliteration of pancreatic beta cells or the incompetent sensitivity of insulin at the target tissue. Methods: In the present study, selected compounds (Abrotandiol, Abrotanone, Lariciresinol, Pinoresinol, Syringaresinol and Taxiresinol) from Perovskia atriplicifolia were evaluated for antidiabetic potentials using molecular docking simulations and computational tools. Results: All selected compounds possess moderate to strong respective activities against aldose reductase, DPP-IV, PTPB, insulin receptor and PPAR-g. Selected compounds that include Abrotandiol, Lariciresinol, Pinoresinol, Syringaresinol, Abrotanone and Taxiresinol have shown highest binding energies of ΔG = -9.3 kcal/mol, -8.9 kcal/mol, -8.9 kcal/mol, -8.8 kcal/mol, -8.8 kcal/mol and -7.6 kcal/mol respectively against PPAR-g. However, out of six compounds, Abrotanone has shown strong potential binding energy against all selected targets, i.e. ΔG = -7.8 kcal/mol with aldose reductase, ΔG = -10.3 kcal/mol with DPP-IV, ΔG = -9.3 kcal/mol with PTPB and ΔG = -8.3 kcal/mol with insulin receptors. Conclusion: The present study proposed that all selected compounds possess antidiabetic activity. However, Abrotanone has a strong antidiabetic potential. This assumption provides better insight to evaluate further these compounds for in vitro and in vivo testing against diabetes in future.

Background: Lysyl oxidase-like 2 (LOXL2) has recently been explored as extremely pivotal protein involved in angiogenesis which results in metastasis of numerous types of cancers. Hence, LOXL2 is an exciting new target for drug development against tumor progression and its spread to distant organs. Newly synthesized derivatives of natural phenolic antioxidant guaiacol (T1 to T8) were evaluated for their potential as anti-angiogenic agents using in silico approach. The drug likeness properties and toxicity of the synthesized derivatives have also been determined. Active binding sites of LOXL2 protein were determined by online server DoGSiteScorer, and lead–target interactions and conformations of pose analysis were done by using AutoDock Vina and Discovery Studio 4.0. The GUSAR model was applied to find the toxicity and ADMET properties. On the other hand, the chemoinformatics prediction was also performed using online FAF Drug Server and Molinspiration online server. Results: Lead molecules from T1 to T8 showed promising binding affinity values, especially T5 and T8 showed best fit in the binding pocket of target enzyme (binding energies − 7.9 and 8.0 kcal/Mol, respectively). The stability of docked complexes was further evaluated using molecular dynamic simulation studies using GROMACS force field, and both leads (T5 and T8) were found to be strongly bounded to the active binding sites. The ADMET results revealed that all experimental molecules were virtually nontoxic and showed compliance with rule of five. Conclusion: The present work will further enable researchers to understand how computer-aided drug designing tools may help to expedite new drug discovery process in a minimum cost.

Serotonin reuptake inhibitors were recently reported to possess antimicrobial potentials, potentiate activity of several antibiotics, reverse multidrug resistant phenotypes of bacteria and make them susceptible to previously resistant drugs. We investigated antimicrobial potentials of sertraline (SR) against ATCC strains, clinical isolates of Staphylococcus aureus, Escherichia coliand Pseudomonas aeruginosaalone and in-combination with seven antibiotics. Antifungal activity was investigated against four fungal strains including Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, and Fusarium solani.Intrinsic antibacterial action and Minimum Inhibitory Concentrations (MICs) were determined using well assay, nutrient broth and agar dilution techniques. Disk diffusion and nutrient broth methods were used to study bacterial susceptibility to SR. Minimum Fungicidal Concentrations (MFCs) of SR were determined using Sabouraud dextrose Agar (SDA). Sertraline possesses strong intrinsic antibacterial, antifungal activities and has augmented the antibacterial activities of antibiotics. For S. aureusATCC 6538, E. coliATCC 8739 and P. aeruginosaATCC 9027, the MICs of SR were 20, 40 and 60 μg ml−1, respectively, whereas 55.5% clinical isolates of S. aureusand 50% of E. colistrains were inhibited at 20 and 60 μg ml−1of SR, respectively. Among the tested fungi, 60% of A. nigerand A. fumigatuswere inhibited at 40 and 80 μg ml−1, respectively. MFCs were 60 and 80 μg ml−1for A. flavusand F. solani,respectively.Antibacterial activities of all antibiotics were significantly increased (p< 0.001) with the addition of SR 100 μg ml−1against all tested bacteria. Combination study revealed that SR had significantly increased the activity of antibiotics, and some previously resistant strains were made susceptible. Thus antidepressants are potential sources of resistance modifying agents when used in combination.

• Three different types of cross flow were studied with streamwise flow. • The investigations of Casson fluid parameter are carried out in presence of stretching sheet effect. • The closed form solutions are found for all types of flow. • All the results are depend upon a single parameter known as Casson material parameter. The boundary layer flow for the Casson fluid generated by a stretching sheet with cross flows is studied. In this paper we analyzed three different cases of cross flow with streamwise flow. The cross flow in the first case, is generated due to uniform transverse free stream while the stretching surface is at rest. In second case the cross flow is caused by the motion of stretching surface with uniform transverse velocity and the cross flow in third case deals with the transverse shearing motion of the stretching surface. In all the case, possible one parameter solutions appear namely material parameter. The similarity solution for the present model is obtained from the Weidman solution by using some proper transformation. The velocity profiles and the wall shearing parameters for all type of flows are displayed in graphical form. It is depicted that Casson fluid material parameter β causes reduction in stream wise flow, uniform transverse plate motion and transverse shearing motion. Moreover, it is found that the magnitude of longitudinal wall shear stress parameter is greater than or equal to transverse wall shear stress for β. [ABSTRACT FROM AUTHOR]

Nepeta suavisis used in traditional medicine for treatment of abdominal spasm (colic). The tricyclic clerodane type diterpene, nepetolide, isolated for the first time from Nepeta suavis. was evaluated for Ca++antagonist and antispasmodic activities. When studied in isolated rabbit jejunum, nepetolide caused concentration-dependent (0.03–100 μM) relaxation of spontaneous and high K+(80 mM)-induced contractions, like that caused by verapamil, indicating that nepetolide exhibits spasmolytic activity, possibly mediated through Ca++channel blocking action, which provides scientific explanation for the medicinal application of Nepeta suavisas an antispasmodic agent.

A high molecular weight serine protease has been purified to electrophoretic homogeneity from the seeds of Caesalpinia bonducellaFlem. (Caesalpiniaceae) by the combination of size exclusion and ion exchange chromatography. About 524 fold purification was achieved with an overall recovery of 6.8%. The specific activity was found to be 86 U/mg/min at pH 8.0. The calculated Kmand Vmaxwere 1.66 mg/mL and 496.68 units/min per mg of protein, respectively. The molecular mass was estimated to be about 63 kDa by sodium dodecyl sulfate PAGE. The enzyme showed optimum activity at pH 8.0 and exhibited its highest activity at 40°C. The enzyme was strongly inhibited by 2mM phenylmethylsulfonyl fluoride (PMSF), suggesting the presence of a serine residue at the active site. PMSF showed a pure competitive type of inhibition with the serine protease enzyme. It was observed that enzyme activity was enhanced in the presence of dications and was active against a variety of modified substrates and natural proteins.