Current Pharmaceutical Biotechnology - Volume 20, Issue 14, 2019

The methods of chemical structural alteration of small organic molecules by using microbes (fungi, bacteria, yeast, etc.) are gaining tremendous attention to obtain structurally novel and therapeutically potential leads. The regiospecific mild environmental friendly reaction conditions with the ability of novel chemical structural modification in compounds categorize this technique; a distinguished and unique way to obtain medicinally important drugs and their in vivo mimic metabolites with costeffective and timely manner. This review article shortly addresses the immense pharmaceutical importance of microbial transformation methods in drug designing and development as well as the role of CYP450 enzymes in fungi to obtain in vivo drug metabolites for toxicological studies.

Blood Brain Barrier (BBB) is the collection of vessels of blood with special properties of permeability that allow a limited range of drug and compounds to pass through it. The BBB plays a vital role in maintaining balance between intracellular and extracellular environment for brain. Brain Capillary Endothelial Cells (BECs) act as vehicle for transport and the transport mechanisms across BBB involve active and passive diffusion of compounds. Efficient prediction models of BBB permeability can be vital at the preliminary stages of drug development. There have been persistent efforts in identifying the prediction of BBB permeability of compounds employing multiple machine learning methods in an attempt to minimize the attrition rate of drug candidates taking up preclinical and clinical trials. However, there is an urgent need to review the progress of such machine learning derived prediction models in the prediction of BBB permeability. In the current article, we have analyzed the recently developed prediction model for BBB permeability using machine learning.

There has been significant growth in the herbal drugs market around the world, over the last few decades due to growing awareness among people about the rising cost as well as side effects related to the use of synthetic drugs. Herbal medicine has been used in traditional medicinal systems around the world, especially India where the oldest systems of medicine namely Ayurveda, Siddha, and Unani make use of more than 90% plant-based formulations. India is rich in medicinal and herbal plants resources that provide for both the health care needs of rural India as well as the source of raw material for therapeutic agents required in the production of traditional and modern medicine. This review article presents an overview of the knowledge of Indian herbal plants based medicine in the national and international market and the trends in its production, sustainability, and promotion.

Celiac Disease (CD) is a complex autoimmune enteropathy of the small intestine that commonly occurs in genetically predisposed individuals due to intake of gluten and related proteins. Gluten consumption, duration of breast-feeding, various infections, especially frequent intestinal infections, vaccinations and use of antibiotics can be linked to CD. It is predicted that it affects 1% of the global population and its incidence rate is increasing. Most of the people with the HLA-DQ2 or HLADQ8 are at a higher risk of developing this disease. The link between infections and autoimmune diseases has been very much considered in recent years. In several studies, we explained that pathogenic and non-pathogenic microorganisms might have multiple roles in initiation, exacerbation, and development of Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). In various studies, the relationship between infections caused by viruses, such as Epstein-Barr Virus (EBV), Rotavirus, Hepatitis C (HCV), Hepatitis B virus (HBV), Cytomegalovirus (CMV), and Influenza virus, and parasites including Giardia spp. and Toxoplasma gondii with CD has been raised. However, increasing evidence proposes that some of these microorganisms, especially helminths, can also have protective and even therapeutic roles in the CD process. Therefore, in order to determine the role of microorganisms in the process of this disease, we attempted to summarize the evidence suggesting the role of viral and parasitic agents in pathogenesis of CD.

Objective: Transfersomes are highly flexible vesicles that are capable of passing through pores smaller than their own sizes due to their elastochemical characteristics, and thus play a key role in drug delivery to the skin. Methods: In this study, we used transdermal delivery of growth hormone-encapsulated transferosomes (F1 and F2) as antiaging strategy, with the resulting effects being subsequently evaluated. The size, distribution and zeta potential of the particles, together with the in vitro skin permeation and biological activity of the growth hormone loaded onto the transfersomes were measured. Results: The data demonstrated that treatment of fibroblasts with encapsulated hGH increased cell migration, proliferation and collagen I and III gene expression. According to our results, the maximum amount of growth hormone that passes through the skin during a 24 h time period was 489.54 and 248.46 ng/cm3, for the F1 and F2 transfersomes, respectively. In addition, it was determined that F1 formula as the more efficient carrier, showed no toxicity against cells. With regard to fibroblasts, as one of the most important cells involved in collagen synthesis, skin aging and wound healing, concentrations of growth hormone encapsulated in transferosomes that had an effect on fibroblast growth and division, were determined. The results demonstrated that effective concentrations of the encapsulated growth hormone increased the expression of collagen I and collagen III genes. Conclusion: Furthermore, analyzing the rate of fibroblast cell migration showed that migration increased significantly at 700 ng/ml growth hormone concentrations, as compared to that of the control.

Background & Objective: Pseudomonas aeruginosa shows resistance to a large number of antibiotics, including carbapenems and third generation cephalosporin. According to the World Health Organization global report published in February 2017, Pseudomonas aeruginosa is on the priority list among resistant bacteria, for which new antibiotics are urgently needed. Peptidoglycan serves as a good target for the discovery of novel antimicrobial drugs. Methods: Biosynthesis of peptidoglycan is a multi-step process involving four mur enzymes. Among these enzymes, UDP-N-acetylmuramate-L-alanine ligase (MurC) is considered to be an excellent target for the design of new classes of antimicrobial inhibitors in gram-negative bacteria. Results: In this study, a homology model of Pseudomonas aeruginosa MurC ligase was generated and used for virtual screening of chemical compounds from the ZINC Database. The best screened inhibitor i.e. N, N-dimethyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazole-5-sulfonamide was then validated experimentally through inhibition assay. Conclusion: The presented results based on combined computational and in vitro analysis open up new horizons for the development of novel antimicrobials against this pathogen.

Objective: In this study, chitosan/alginate-ellagic acid sustained-release microspheres were prepared, and the effect of sustained-release microspheres on preadipocyte adipogenic differentiation was analyzed. Methods: Chitosan/alginate-ellagic acid microspheres were prepared and identified by scanning electron microscopy (SEM) and infrared spectroscopy (IR). The drug release rates were measured at pH 6.8, 7.0, 7.2, 7.4 to determine sustained release of ellagic acid from microspheres. The effects of 0.1, 1, 10 mg/L chitosan/alginate-ellagic acid microsphere on 3T3-F442A preadipocyte proliferation were determined by Methyl thiazolyl tetrazolium assay (MTT), and cell morphology was checked by hematoxylin/ eosin staining (HE staining). The effect of chitosan/alginate-ellagic acid microspheres on preadipocyte adipogenic differentiation was also determined by Oil red O staining, and lipogenesis was measured by isopropanol extraction. The molecular mechanism was investigated by detecting the mRNA expression of CCAAT/enhancer binding protein alpha (C/EBPα) and peroxisome proliferatorsactivated receptor gamma (PPARγ). Results: Chitosan/alginate-ellagic acid sustained-release microspheres were successfully prepared, and the inhibition of proliferation and adipogenic differentiation of preadipocytes was found to be dosedependent. The mechanism of differentiation inhibition was found to be closely related to the expression of transcription factor C/EBPα and PPARγ. Conclusion: Chitosan/alginate can be used as a good material to prepare ellagic acid sustained-release microspheres, and these microspheres can be used for treating the obesity.

Background: Staphylococcus aureus nosocomial infections with a high mortality rate in human and animals have been reported to associate with bacterial biofilm formation, along with the secretion of numerous virulence factors. Therefore, the inhibition of biofilm formation and attenuation of virulence determinants are considered as a promising solution to combat the spread of S. aureus infections. Modern trends in antibiofilm therapies have opted for the active agents that are biocompatible, biodegradable, non-toxic and cost-effective. Owning the aforementioned properties, chitosan, a natural N-acetylated carbohydrate biopolymer derived from chitin, has been favorably employed. Recently, the chitosan structure has been chemically modified into Chitooligosaccharides (COS) to overcome its limited solubility in water, thus widening chitosan applications in modern antibiofilm research. In the present study, we have investigated the antibacterial, antibiofilm and anti-virulence activities against S. aureus of COS of different molecular weights dissolved in neutral water. Methods: The study of bactericidal activity was performed using the micro-dilution method while the biofilm inhibition assay was performed using crystal-violet staining method and confirmed by scanning electron microscopic analysis. The inhibition of amyloid protein production was confirmed by Congo Red staining. Results: Results showed that low molecular weight COS exhibited bactericidal activity and reduced the bacterial amylogenesis, hemolytic activity as well as H2O2 resistance properties, while slightly inhibiting biofilm formation. The present study provides a new insight for further applications of the water-soluble COS as a safe and cost-effective drug for the treatment of S. aureus biofilm-associated infections. Conclusion: Reducing the molecular weight of chitosan in the form of COS has become an effective strategy to maintain chitosan biological activity while improving its water solubility. The low molecular weight COS investigated in this study have effectively performed antibacterial, antibiofilm and antivirulence properties against S. aureus.