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The marine environment is emerging as a biodiversity resource for the discovery of natural molecules or chemical scaffolds with pharmaceutical activity. Marine microbes have a tremendous ability to sense and respond to their surroundings to survive in a stressful environment by producing different molecules. As oxidative stress is directly or indirectly involved in various pathological conditions in humans, we believe that marine-derived antioxidant molecules will have a great prospect as a novel antioxidant molecule. We, in this work, explored the marine microbial resources from the Gulf of Mannar, Bay of Bengal, India. High-throughput screening of antioxidant molecule producing marine microbes has revealed that extract from

In this study, one bioactive coumarin analog was obtained as a result of biotransformation of three inactive coumarin derivatives by free cells of Candida albicans. The bioactive analog was purified by Column chromatography and HPLC. The presence of coumarin moiety in the biotrasformed product was confirmed by λmax at 350–400 nm and FT-IR spectrum. The structure of the purified compound established by LC–MS and 1H NMR suggests the chances of biotransformation of 7-(3-(Cyclopropylamino)-2-hydroxypropoxy)-4-methyl-2H-chromen-2-one (MW 289 Da) into 7-(3-Cyclopropylamino-2-hydroxy-propoxy)-4-methoxymethyl-chromen-2-one or 7-(3-Cyclopropylamino-2-methoxy-propoxy)-4-hydroxymethyl-chromen-2-one as a main product (MW 318 Da). The extra peak of 332 Da in LC–MS further confirms the presence of small proportion of 7-(3-Cyclopropylamino-2-methoxy-propoxy)-4-methoxymethyl-chromen-2-one apart from the main product. Oxidation followed by methylation reaction might be responsible for this conversion. The biotransformed product showed antimicrobial activity against Bacillus pumilus, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and Salmonella typhi followed by decent antioxidant activity (6.756 μg IC50). The efficacy of coumarin-analog on cellular proliferation was found at 40 μM concentration against human breast cancer MDA-MB-231 cells in MTT assay, which is insignificant against normal breast tissue MCF-10A cells at the same concentration. These findings suggest the potential use of C. albicans for achieving pharmacologically active coumarin analogs showing antibacterial, antioxidant and cytotoxic activity.

Here we report epigenomic and transcriptomic changes in a prototypical J774 macrophage after engulfing talc or titanium dioxide particles in presence of estrogen. Macrophages are the first immune cells to engage and clear particles of various nature. A novel paradigm is emerging, that exposure to so-called 'inert' particulates that are considered innocuous is not really free of consequences. We hypothesized that especially the insoluble, non-digestible particles that do not release a known hazardous chemical can be underappreciated agents acting to affect the regulation inside macrophages upon phagocytosis. We performed gene chip microarray profiling and found that talc alone, and especially with oestrogen, has induced a substantially more prominent gene expression change than titanium dioxide; the affected genes were involved in pathways of cell proliferation, immune response and regulation, and, unexpectedly, enzymes and proteins of epigenetic regulation. We therefore tested the DNA methylation profiles of these cells via epigenome-wide bisulphite sequencing and found vast epigenetic changes in hundreds of loci, remarkably after a very short exposure to particles; ELISA assay for methylcytosine levels determined the particles induced an overall decrease in DNA methylation. We found a few loci where both the transcriptional changes and epigenetic changes occurred in the pathways involving immune and inflammatory signalling. Some transcriptomic and epigenomic changes were shared between talc and titanium dioxide, however, it is especially interesting that each of the two particles of similar size and insoluble nature has also induced a specific pattern of gene expression and DNA methylation changes which we report here.

Antimicrobial peptides are one of the important components of innate immune defense system and play a critical role in controlling infections. Although vast sequence and structural diversities exist, AMPs share several common features like cationicity, amphipathicity and membrane permeabilisation as mode of action. In this study, a moderately short cationic and hydrophobic peptides derived from the conserved domains of human glutathione S-transferase (GST) have been shown to have antimicrobial activity against Staphylococcus aureus ATCC 29213 and Klebsiella pneumoniae ATCC 7637 in physiological conditions without any toxicity issues. We further shown here that human GST, a C-terminal region which showed the higher antimicrobial activity, is conserved in the vertebrates. Our results demonstrate the potential of human GST derived peptides as a template for the development of anti-infective therapeutics.

Natural products have a huge value in pharmaceuticals industry as molecules or templates for discovery or further development of new drugs. It is predicted that, if the marine resources are explored fully, then we will have enough chemically diverse molecules to sustain us for the coming next century. For the discovery of new classes of natural products, polar organisms are emerging as a source of unknown magnitude because recent genetic based studies showed that the diversity of the polar region is much more than previously predicted. In order to survive in the cold, extreme and inhospitable environment conditions, polar organisms produce an array of unique metabolites which confer an advantage and offers protection from predation. Out of all the natural products reported from polar organisms, 38% of them showed bioactivity of pharmaceutical relevance. This high success percentage clearly illustrates the tremendous potential of the polar organisms as a source of new therapeutic agents for infectious and lifestyle associated diseases. We in this review describe the natural products discovered, isolated and characterized from the organisms (both prokaryotes and eukaryotes) found in the polar (Arctic and Antarctic) regions. Further, we discussed the problems encountered and solutions employed by the various researcher during natural product isolation from marine sources.

Hit, Lead & Candidate Discovery Drug repurposing has become a recent trend in drug development programs, where previously developed drugs are explored for hit and redeveloped into potential therapeutic agents for new diseases. Globally, in any drug development program, a series of molecules are synthesized and evaluated for the hypothesized activity. Hits are developed into lead molecules or drugs, whereas the negative ones are shelved in the lab with no immediate use. We in this project took the previously sidelined small chemical molecules to the next level of utility, where previously developed in-house small molecules library are tested for the unexplored biological relevant activity. As biofilm formation and quorum sensing play a vital role in bacterial pathogenesis, we believe that they could be one of the most effective targets for antimicrobial agents. In this study, we report the evaluation of 50 different compounds for anti-biofilm and anti-quorum sensing activity against Pseudomonas aeruginosa. Out of the screened compounds, three hydrazine-carboxamide hybrid derivatives showed promising anti-biofilm property and inhibition of pyocyanin production without any direct antimicrobial activity and cytotoxicity issues. Hydrazine-carboxamide hybrids can be a new class and promising leads for further anti-biofilm and anti-virulence development against microbial infections.

Aims: To evaluate anti-cancer activity of Asparagus racemosus (AR) leaf extract on UOK146, a renal cell carcinoma cell line, and explore its mechanism of action. Materials and Methods: Dried AR leaves were extracted with chloroform and dissolved in DMSO. This extract was applied to UOK146 and cell death was estimated by MTT assay. In addition PRCC-TFE3 fusion transcripts were detected by real time PCR. Results: Extract was found to be cytotoxic with an IC 50 of 0.9 mg/ml as estimated by dose response curve. Antitumor activity of the permissible doses of the extract was assessed by the down regulation of PRCC-TFE3 fusion transcript (38%) responsible for oncogenicity of the UOK146 cell line. No increment in the BAX, a proapoptotic marker level was observed. Conclusions: Evidence of antiproliferative effect, PRCC-TFE3 fusion transcript inhibition and static BAX level clearly indicate that AR extract provides or elicits an apoptosis independent anticancer effect on RCC cells by some specific mechanism of regulation.