Bioinformatics Paradigms in Drug Discovery and Drug Development.

Despite breakthroughs in medical sciences, drug development remains a timeconsuming, expensive, challenging, and inefficient process with a high failure rate for novel therapeutic discoveries. Bioinformatics analysis can speed up drug target identification, drug candidate screening, and refining, but it can also help characterise adverse effects and anticipate drug resistance. Integrated genomics, proteomics, and bioinformatics have resulted in potent new tactics for resolving numerous biochemical problems and establishing new methodologies that result in new biomedical products. As a result, a new research trend emerged to demonstrate the mechanism of therapeutic action, forecast drug resistance, and uncover biomarkers for various disorders. The development of new medications is a complicated procedure. There are two basic approaches to drug design: ligand-based drug design and structure-based drug design. The study of protein structure and function was essential for drug development. Current techniques based on combinatorial approaches such as proteomics, genomics, bioinformatics, molecular docking, and mass spectrometry were applied. This article provides an overview of the combinatorial techniques of proteomics, genomics, and bioinformatics that aid in understanding the drug-creation process.

Bioactivity-guided isolation of potent anxiolytic compounds from leaves of Citrus paradisi.

CONTEXT: Citrus fragrances have been attributed with mood-enhancing properties by aromatherapists. Leaves of this plant have been reported to exert anti-anxiety activity. Till date, no specific phytoconstituent responsible for this has been identified. OBJECTIVE: Isolation of anxiolytic constituent of Citrus paradisi using bioactivity-guided fractionation. MATERIALS AND METHODS: Leaf extracts of four varieties of C. paradisi in petroleum ether, chloroform, methanol and water were evaluated for anti-anxiety activity in mice using elevated plus-maze apparatus. Because of activity in methanol extract, it was used for safety evaluation/acute toxicity studies in animals. Bioactive fraction of methanol extract was subjected to column chromatography and structure of the isolated compound was elucidated by melting point, ultraviolet, infrared, nuclear mass reactor and mass spectroscopy. The isolated constituents were further evaluated for anti-anxiety activity using light/dark model and hole-board model of anxiety. RESULTS: Results showed no mortality at a dose up to 2000 mg/kg body weight that indirectly reflects the safety profile of the leaf extracts. Fractionation of methanol extract led to the isolation of four flavonoids (rutin, quercetin, kaempferol and myricetin). The isolated compounds exhibited significant anxiolytic activity in different animal models. CONCLUSION: The study confirms the presence of four flavonoids responsible for anti-anxiety activity.

Kitchen phytochemicals from Allium cepa - their role in multidrug resistance.

Bacterial resistance to antibiotics is increasingly becoming a concern to public health. Current antibiotics have failed to bring desirable results to many bacterial infections due to multi-resistant strains. So, concerted efforts are being made to curve this with the help of dietary phytohemicals. A number of dietary phytochemical are being put to trials for antimicrobial activity; however it is worthwhile to search such a part of diet that is very frequently used by major population. Keeping this view in mind an effort has been made to evaluate the antimicrobial activity of most common vegetable component Allium cepa. Methanolic and aqueous extracts were prepared from Allium cepa and antibacterial activity was tested on four pathogenic bacteria (Gram-positive and Gram negative) Staphylococcus aureus, Bacillus Subtilis, Escherichia coli and Pseudomonas aeruginosa using Disc diffusion method and Minimum inhibitory concentration by the Microtitre well plate method. Conventional antibiotic discs of Tetracycline and Gentamycin were used as positive control. Among the two extracts, methanolic extract exhibited a significant antimicrobial activity on the test organisms Ps. aeruginosa (17.5mm) and B. subtilis (11.3mm). The minimum inhibitory concentration value for Ps. aeruginosa was 500µl and for B. subtilis was 250µl for methanolic extract. The growth of other two bacteria i.e. E. coli and S. aureus were not inhibited by methanolic as well as aqueous extract that indicates non susceptibility to aqueous and methanol extract of Allium cepa. From the study, it was concluded that the commonly used Allium cepa possess potent antibacterial property against Bacillus Subtilis and Pseudomonas aeruginosa.

Innate antioxidant activity of some traditional formulations.

Herbal medicine is the oldest form of healthcare known to humanity. Recently, much attention is being directed toward the use of antioxidants. There are some very commonly used Ayurvedic preparations that might have inbuilt antioxidant activity, and their therapeutic potential can be partially attributable to its antioxidant activity. Hence, it was proposed to find out antioxidant activity of such common formulations. Estimation of innate antioxidant activity of some commonly used traditional formulations. In this study, five formulations were evaluated for antioxidant activity in comparison to gallic acid (standard) using the in vitro reducing power method and superoxide radical scavenging activity by dimethyl sulfoxide method followed by calculation of scavenging activity and inhibitory concentration 50% (IC50). The result shows that Ayurvedic drug extracts possess good reducing power and antioxidant activity. Laxmivilas Ras shows higher reducing power ranging from 117 ± 0.021 to 0.176 ± 0.012 as compared to other extracts. The drug extracts were also found to be an efficient scavenger of superoxide radical. The IC50 values for Laxmivilas Ras, Agnitundi Vati, Ajmodadi Churna, Tribhuvankirti Rasa, gallic acid (standard) and Sitopladi Churna, were found to be 50.07, 98.41, 105.13, 116.39, 176.80, and 200.17, respectively. From this study, it can be concluded that the above Ayurvedic formulations possess antioxidant property. However, work could be initiated on the isolation and identification of these antioxidant components.

MicroRNA therapeutics: Discovering novel targets and developing specific therapy.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in diverse biological process. They act as intracellular mediators that are necessary for various biological processes. MicroRNAs targeting pathways of human disease provide a new and potential powerful candidate for therapeutic intervention against various pathological conditions. Even though, the information about miRNA biology has significantly enriched but we still do not completely understand the mechanism of miRNA gene regulation. Various groups across the globe and pharmaceutical companies are conducting research and developments to explore miRNA based therapy and build a whole new area of miroRNA therapeutics. Consequently, few miRNAs have entered the preclinical and clinical stage and soon might be available in the market for use in humans.