Novel Furan Coupled Quinoline Diamide Hybrid Scaffolds as Potent Antitubercular Agents: Design, Synthesis and Molecular Modelling.

BACKGROUND: A novel series of 2-[(2-{[2-(furan-2-yl) quinolin-4-yl] carbonyl} hydrazinyl) carbonyl] benzoic acid, -4-oxobut-2-enoic acid and -4-oxobutanoic acids were synthesized and screened for in vitro antitubercular activity. OBJECTIVES: In the present investigation, we describe the synthesis and biological screening of furan C-2 quinoline coupled diamides for antitubercular activity. METHODS: The mycobacterium tuberculai testing was carried out by MABA method and molecular docking studies were done by open-source molecular docking program, Autovina, using Pyrx 0.8 interface. RESULTS: The results revealed that the compounds inhibited the growth of H37Rv strain at concentrations as low as 1.6 to 12 µg/ml. Molecular binding of furan, quinoline and diamide (FQD) derivatives on five targets was good and these compounds fit very well within the binding domain of the target protein. CONCLUSION: The synthesized FQD derivatives exhibited moderate to good inhibition activity especially compounds 5f, 5b and 8a exhibited very good inhibition activity due to the presence of three different scaffolds, such as INH, phenyl ketobutyric acid and fluoroquinolines. Hybridized molecules might have multiple modes of action / inhibit more than one tubercular target and could pave way for novel drug discovery in the field of tuberculosis.

Repositioning of molsidomine for its efficacy in diabetes induced erectile dysfunction in rats: In silico, in vitro and in vivo approach.

BACKGROUND: Well known risk factors for diabetic erectile dysfunction include impaired nitric oxide synthesis and endothelial dysfunction. We proposed to evaluate the efficacy of nitric oxide donor, molsidomine in rat model of diabetic erectile dysfunction. METHODS: Streptozotocin (52mg/kg, ip) induced diabetic male rats were treated with molsidomine (5 and 10mg/kg, po) for 8 weeks. The sexual behaviour of male rat in presence of the female rat in oestrous phase was observed at the end of study. The effect of treatment on serum testosterone level, sperm parameters and penile tissue histopathology was also evaluated. Further anti-inflammatory activity and antioxidant potential of molsidomine was evaluated by in vitro method. In silico docking study was carried out to appreciate binding conformation of the molsidomine to its plausible target, phosphodiesterase enzyme. RESULTS: Molsidomine significantly and dose dependently increased sexual behaviour, sperm count and serum testosterone level in diabetic rats. Further, the protective effect of molsidomine was also substantiated by pathological changes in the architect of the penile tissue. Molsidomine showed good membrane stability accounting for its significant anti-inflammatory action and also significantly scavenged DPPH radical activity showing its antioxidant action. Molsidomine was found to settle well in the active site of PDE-5 enzyme with less binding affinity than the standard drug sildenafil. CONCLUSION: The results highlight the rationale behind the repositioning of molsidomine therapy for the management of diabetic erectile dysfunction.

In Silico Drug-Designing Studies on Flavanoids as Anticolon Cancer Agents: Pharmacophore Mapping, Molecular Docking, and Monte Carlo Method-Based QSAR Modeling.

In silico molecular modeling studies were carried out on some newly synthesized flavanoid analogues. Search for potential targets for these compounds was performed using pharmacophore-mapping algorithm employing inverse screening of some representative compounds to a large set of pharmacophore models constructed from human target proteins. Further, molecular docking studies were carried out to assess binding affinity of these compounds to proteins mediating tumor growth. In vitro anticancer studies were carried out on colon cancer cell lines (HCT116) to assess validity of this approach for target identification of the new compounds. Further important structural features of compounds for anticolon cancer activity were assessed using Monte Carlo-based SMILES and hydrogen graph-Based QSAR studies. In conclusion this study have depicted successful and stepwise application of pharmacophore mapping, molecular docking, and QSAR studies in target identification and lead optimization of flavonoids.

Curcumin loaded self assembled lipid-biopolymer nanoparticles for functional food applications.

The supramolecular nano-assemblies formed by electrostatic interactions of two oppositely charged lipid and polymer have been made and used as nanocarriers for curcumin to address its bioavailability and solubility issues. These curcumin encapsulated nano-supramolecular assemblies were characterized with respect to their size (dynamic light scattering), morphology (TEM, SEM), zeta potential (Laser Doppler Velocimetry), encapsulation efficiency (EE), curcumin loading (CL) etc. Stability of the nano-assemblies was assessed at different storage times as a function of varying pH and temperature. The physicochemical characterization of nano-assemblies was performed using Fourier Transform Infra Red Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC). The in-vitro antioxidant lipid peroxidation (TBARS), radical scavenging (DPPH, NO, H2O2, reducing power) activity assays of powdered curcumin and nano-encapsulated curcumin were performed. It was found that nano-encapsulated curcumin were roughly spherical in shape, presented high positive zeta potential (>30 mV), monodisperse (polydispersity index <0.3), amorphous in nature, stable in the pH range of 2-6 and have enhanced antioxidant potency in comparison to crystalline curcumin in aqueous media. In conclusion, the curcumin encapsulated nanocarriers system has great potential as functional food ingredient of natural origin.

Corrosion behavior of titanium boride composite coating fabricated on commercially pure titanium in Ringer's solution for bioimplant applications.

The boriding of commercially pure titanium was performed at 850°C, 910°C, and 1050°C for varied soaking periods (1, 3 and 5h) to enhance the surface properties desirable for bioimplant applications. The coating developed was characterized for the evolution of phases, microstructure and morphology, microhardness, and consequent corrosion behavior in the Ringer's solution. Formation of the TiB2 layer at the outermost surface followed by the TiB whiskers across the borided CpTi is unveiled. Total thickness of the composite layer on the substrates borided at 850, 910, and 1050°C for 5h was found to be 19.1, 26.4, and 18.2µm respectively which includes <3µm thick TiB2 layer. The presence of TiB2 phase was attributed to the high hardness ~2968Hv15gf of the composite coating. The anodic polarization studies in the simulated body fluid unveiled a reduction in the pitting corrosion resistance after boriding the CpTi specimens. However, this value is >0.55VSCE (electrochemical potential in in-vivo physiological environment) and hence remains within the safe region. Both the untreated and borided CpTi specimens show two passive zones associated with different passivation current densities. Among the CpTi borided at various times and temperatures, a 3h treated shows better corrosion resistance. The corrosion of borided CpTi occurred through the dissolution of TiB2.

Natural polyphenols in the management of major depression.

INTRODUCTION: Natural polyphenols, the non-essential micronutrients, found in array of plant products, are known to affect various physiological and biochemical functions in the body. Studies have shown the protective effect of these polyphenols in different neurological and mental disorders. These polyphenols modulate monoaminergic neurotransmission in the brain and thus possess antidepressant-like activity at least in animal models of depression. AREAS COVERED: The present review discusses the use of these natural polyphenols in the treatment of major depression. The review article discusses the antidepressant potential of some important polyphenols such as amentoflavone, apigenin, chlorogenic acid, curcumin, ferulic acid, hesperidin, rutin, quercetin, naringenin, resveratrol, ellagic acid, nobiletin and proanthocyanidins. The mechanism of action of these polyphenols in the treatment of major depression is also discussed in detail. EXPERT OPINION: There is an exciting prospect in the discovery of natural polyphenols as therapeutic agents in the treatment of major depression.

Hydroxyapatite coating on stainless steel pre-coated with bovine serum albumin at ambient conditions.

A biomimetic process for coating of nanosized hydroxyapatite on stainless steel, which capitalises the dual nature of the protein bovine serum albumin in both metal binding and a strong affinity for calcium ions, has been developed. The novelty of the process lies in pre-conditioning the metallic surface using the above protein prior to its mineralization with hydroxyapatite at ambient conditions. The microporous morphology of these coatings may provide favourable solubility and resorbability as desired by many orthopaedic and orthodontic applications.