Ellagic acid restored lead-induced nephrotoxicity by anti-inflammatory, anti-apoptotic and free radical scavenging activities.

INTRODUCTION: long-term environmental and occupational exposure to lead, which is a ubiquitous industrial pollutant, causes significant damage to tissues of kidney. This report aims to address this debilitating issue. A natural polyphenolic compound, Ellagic acid (EA) is having numerous potential medicinal properties. In this present study nephroprotective effects of EA has been evaluated in a rodent model with lead-induced toxicity. METHODS: Rats were treated with EA doses of 50 mg/kg and 25 mg/kg and simultaneously co-administered with lead acetate (60 mg/kg) for 2 months through oral route. The extent to which EA treatment provides nephroprotective effect was estimated by measurement of serum biomarkers, tissue antioxidants, inflammatory mediators, apoptosis, autophagy pathway and histological examination. RESULTS: EA treatment caused significant restoration in the level of serum biomarkers, tissue antioxidants and histological architecture of renal tissue. Treatment with either of the doses of EA causes restoration of pro-inflammatory mediators to approximately pre-exposure concentration. This phenomena is caused by suppression of expression levels of inflammatory molecules like tumour necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), as well as functional expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it was also observed that EA suppressed apoptotic and autophagic pathway by reduction of expression of light chain 3B (LC3B) level which are the oxidative DNA damage markers of renal tissue. CONCLUSION: It can be safely concluded that EA provides protection against lead-induced nephrotoxicity to a significant degree.

Antimicrobial metabolites from marine microorganisms.

Marine ecological niches have recently been described as "particularly promising" sources for search of new antimicrobials to combat antibiotic-resistant strains of pathogenic microorganisms. Marine organisms are excellent sources for many industrial products, but they are partly explored. Over 30 000 compounds have been isolated from marine sources. Bacteria, fungi, and cyanobacteria obtained from various marine sources secret several industrially useful bioactive compounds, possessing antibacterial, antifungal, and antimycobacterial activities. Sustainable cultivation methods for promising marine organisms and biotechnological processes for selected compounds can be developed, along with the establishment of biosensors for monitoring the target compounds. The semisynthetic modifications of marine-based bioactive compounds produce their new derivatives, structural analogs and mimetics that could serve as novel lead compounds against resistant pathogens. The present review focuses on promising antimicrobial compounds isolated from marine microbes from 1991-2013.

Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach.

A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-TB) against Mycobacterium tuberculosis. Molecular modeling, pharmacophore constructed using GALAHAD to produce an effective alignment of data set and evaluated by Pareto ranking. The pharmacophore features were filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis, which is one of the key enzymes involved in type II fatty acid biosynthesis pathway of M. tuberculosis. Compound 6a27 showed the H-bond with NAD(+), whereas compound 6a26 showed H-bonds with Tyr158, Thr196, Met199 and NAD(+) that fitted well into the binding pocket of target InhA. The alkoxy linker bridge and acceptor groups with benzene ring were advantageous for anti-TB activity, which merit further investigation.

Controlled release of therapeutics using interpenetrating polymeric networks.

INTRODUCTION: The ever-increasing developments in pharmaceutical formulations have led to the widespread use of biodegradable polymers in various forms and configurations. In particular, interpenetrating network (IPN) and semi-IPN polymer structures that are capable of releasing drugs in a controlled manner have gained much wider importance in recent years. AREAS COVERED: Recently, IPNs and semi-IPNs have emerged as innovative materials of choice in controlled release (CR) of drugs as the release from these systems depends on pH of the media and temperature in addition to the nature of the system. These networks can be prepared as smart hydrogels following chemical or physical crosslinking methods to show remarkable drug release patterns compared to single polymer systems. EXPERT OPINION: A large number of IPNs and semi-IPNs have been reported in the literature. The present review is focused on the preparation methods and their CR properties with reference to anticancer, anti-asthmatic, antibiotic, anti-inflammatory, anti-tuberculosis and antihypertensive drugs, as majority of these drugs have been reported to be the ideal choices for using IPNs and semi-IPNs.

Enoyl ACP reductase as effective target for the synthesized novel antitubercular drugs: a-state-of-the-art.

The emergence of drug resistant strains of important human pathogens has created an urgent necessity to find new targets and novel antitubercular agents. According to the literature survey, we noticed that enoyl ACP reductase is one of the most promising targets. This enzyme is the most important catalyst for the FAS II synthesis of mycolic acid, which is the most essential component of the mycobacterial cell wall. This review summarizes the progress made in the design of enoyl ACP reductase inhibitors and the role played by 3D-structure of the enzyme in drug design process.

Design, synthesis, molecular docking and 3D-QSAR studies of potent inhibitors of enoyl-acyl carrier protein reductase as potential antimycobacterial agents.

In order to develop a lead antimycobacterium tuberculosis compound, a series of 52, novel pyrrole hydrazine derivatives have been synthesized and screened which target the essential enoyl-ACP reductase. The binding mode of the compounds at the active site of enoyl-ACP reductase was explored using surflex-docking method. The binding model suggests one or two hydrogen bonding interactions between pyrrole hydrazones and InhA enzyme. Highly active compound 5r (MIC 0.2 µg/mL) showed hydrogen bonding interactions with Tyr158 and NAD(+) in the same manner as those of ligands PT70 and triclosan. The CoMFA and CoMSIA models generated with database alignment were the best in terms of overall statistics. The predictive ability of the CoMFA and CoMSIA models was determined using a test set of 13 compounds, which gave predictive correlation coefficients (r(pred)(2)) of 0.896 and 0.930, respectively.

Protective effect of menthol on ß-amyloid peptide induced cognitive deficits in mice.

Cognitive impairment is a multidimensional concept that subsumes the attention and concentration, learning and memory, problem-solving ability, visuospatial abilities, mental flexibility, psychomotor efficiency and manual dexterity. The intrinsic mechanisms of the behavioural effects may involve neuronal damage in the brain structure. A lower concentration of glutamate receptor co-agonists in the striatum indicates the general malfunction of the brain glutamatergic system. It is suggested that a selective decrease in hippocampal glutamate concentration may account for deterioration in learning and memory process, considering the important role of this neurotransmitter in the cognitive functions. Nootropic agents like piracetam and anticholinesterase inhibitors are commonly used for improving memory, mood and behaviours. The present study was undertaken to assess the nootropic potential of menthol on learning and memory employing exteroceptive and interoceptive behavioral model in young and aged mice. To delineate the mechanism by which menthol decreases cognitive impairment and protect the brain, various biochemical parameters such as brain glutamate, glycine, glutathione and thiobarbituric acid reactive substances were determined. Menthol produced significant improvement in learning and memory. Menthol exhibited excellent antioxidant effect and maintain glutamate concentration in various region of the mouse brain for management of preliminary symptoms of memory impairment.