Current Chemical Biology - Volume 13, Issue 3, 2019

Background: Immunomodulation-based therapy has achieved a breakthrough in the last decade, which stimulates the passion of searching for potential immunomodulatory substances in recent years. Objective: Marine natural products are a unique source of immunomodulatory substances. This paper summarized the emerging marine natural small-molecules and related synthesized derivatives with immunomodulatory activities to provide readers an overview of these bioactive molecules and their potential in immunomodulation therapy. Conclusion: An increasing number of immunomodulatory marine small-molecules with diverse intriguing structure-skeletons were discovered. They may serve as a basis for further studies of marine natural products for their chemistry, related mechanism of action and structure- activity relationships.

Background: Objective: Various natural gums can be synergistically used in nanoparticulate drug delivery systems to treat cardiovascular diseases. Nanotechnology has been integrated into healthcare in terms of theranostics. In this review, we consider various natural gums that can be used for the preparation of nanoparticles and their role to treat cardiovascular disease. Methods: Nanoparticles can carry drugs at nanoscales and deliver them to the targeted sites with the desired pattern of drug release. They have specialized uptake mechanisms (e.g. - absorptive endocytosis) which improve the bioavailability of drugs. Results: By considering cardiovascular diseases at the molecular level, it is possible to modify the materials with nanotechnology and apply nano-formulations efficiently as compared with conventional preparations, due to the fact that the extracellular matrix (ECM) comprises components at the nanoscale range. The interactions of ECM components with cellular components occur at the nanoscale, therefore the nanomaterials have the potential to maintain the nanoscale properties of cells. The synthetic materials used to develop the nanoparticulate drug delivery system may cause toxicity. Conclusion: This problem can be overcome by using natural polymers. Natural gums can be used in nanoparticulate drug delivery systems as reducing and stabilizing agents and in some cases; they may directly or indirectly influence the rate of drug release and absorption from the preparation.

Background: Takeda G-protein receptor 5 (TGR5) via glucagon-like peptide release and insulin signaling underlies antidiabetic roles of TGR5 agonists. Chromolaena Odorata- derived flavonoid-5,7-dihydroxy-6-4-dimethoxyflavanone (COF) has been identified as (TGR5) agonist. The structural basis for their interaction has not been studied. Objective: This study aimed at providing both structural and dynamic insights into COF/TGR5 interaction. Methods: Classical GPCR activation signatures (TMIII-TMVI ionic lock, toggle switches, internal water pathway) using classical MD simulation have been used. Results: Y893.29, N933.33 and E1695.43 are key residues found to be involved in ligand binding; the continuous internal water pathway connects hydrophilic groups of the ligand to the TMIII-TMVI interface in COF-bound state, TMIII-TMVI ionic locks ruptures in COF-TGR5 complex but not antagonist-bound state, and ruptured ionic lock is associated with the evolution of active-state “VPVAM” (analogous to “NPxxY”) conformation. Dihedral angles (c2) calculated along the trajectory strongly suggest W2376.48 as a ligand-dependent toggle switch. Conclusion: TGR5 evolves active state conformation from a starting intermediate state conformation when bound to COF, which further supports its underlying anti-diabetic activities.

Background: Silver nanoparticles have a profound role in the field of high sensitivity biomolecular detection, catalysis, biosensors and medicine. In the present study, aqueous extract of Dracocephalum kotschyi has been used for the synthesis of silver nanoparticles. Objective: In this study, we evaluated the antioxidant features and the possibility of biosynthesis of AgNPs using an aqueous extract of Dracocephalum kotschyi and also evaluated the antibacterial activities of the synthesized nanoparticles. Methods: An eco-friendly and cost-effective protocol for the synthesis of Ag nanoparticles by utilizing a renewable natural resource, aqueous solution of Dracocephalum kotschyi, was proposed. Synthesized nanoparticles were characterized by UV–Vis spectroscopy, SEM, EDS, and XRD pattern. Results: At first, the extract of Dracocephalum kotschyi was assessed to determine and confirm the presence of an antioxidant feature. Resuscitation of one mM silver nitrate solution was carried out by the herbal extract. The solution containing AgNPs obtained from green synthesis had a maximum optical density at 225 nm. In addition, the presence of AgNPs was approved by energy-dispersive X-ray spectroscopy (EDS). Images of the scanning electron microscope demonstrated that the synthesized AgNPs had the shape of rods and the size distribution of 48-51 nm. One of the benefits of this method is a uniform size distribution. Moreover, the effects of reaction time and concentration of the herbal extract were assessed by ultraviolet-visible (UV-Vis) spectroscopy. In the end, we assessed the antibacterial impact of the synthesized AgNPs against some pathogenic bacterial strains. According to the results, the produced nanostructures had a proper impact on two bacteria of Escherichia coli and Staphylococcus aureus. Conclusion: According to the results of the present study, Dracocephalum kotschyi can be a suitable compound for the synthesis of nanostructures due to its indigenous cultivation and great medicinal properties.

Background: Cancer is an extremely fast, unrestrained and pathological propagation of cells. Yet there is no cancer treatment that is 100% efficient against scattered cancer. Heterocycles have been considered as a boon to treat several cancers of which pyrimidine is a core nucleus and holds an important place in cancer chemotherapy which is reflected in the use of drugs such as 5-fluorouracil, erlotinib, gefitinib and caneratinib. Also, many good antitumor active agents possess benzimidazoleas its core nucleus. Objective: To design novel pyrimidine-linked benzimidazoles and to explore their structural requirements related to anticancer potential. Methods: 2D and 3D Quantitative structure–activity relationship (QSAR) studies were carried out on a series of already synthesized 27 pyrimidine-benzimidazole derivatives. Results: Statistically significant and optimum 2D-QSAR model was developed by using step-wise variable multiple linear regression method, yielding correlation coefficient r2 = 0.89, cross-validated squared correlation coefficient q2 = 0.79 and external predictive ability of pred_r2 = 0.73 Best 3D-QSAR model was developed by employing molecular field analysis using step-wise variable k-nearest neighbor method which showed good correlative and predictive abilities in terms of q2 =0.77 and pred_r2= 0.93. Conclusion: These 2D and 3D models were found to give dependable indications which helped to optimize the pyrimidine-benzimidazole derivatives of the data set. The data yielded by 2D- QSAR and 3D-QSAR models will aid in giving better perceptions about structural requirements for developing newer anticancer agents.

Background: The serum copper (Cu) and ceruloplasmin (Cp) concentrations are common blood markers of copper metabolism. In altered physiological conditions, Cp can act as an acute phase reactant and its concentration may increase. Objective: To evaluate specific enzymatic activity of Cp as a potential indicator of Cu status and its correlation with serum Cu level. Methods: Serum Cu levels were estimated as per NIOSH method. Specific enzymatic activity of Cp was determined from enzymatic activity and immune concentration of Cp as per standard methods. The statistical analysis was carried out using the package of social science (SPSS) software. Results: The difference in mean specific enzymatic activity of Cp was statistically significant between clinical and control groups. In control population, the correlation between serum Cu level and specific enzymatic activity of Cp was moderate and statistically significant (r=0.566, p=0.014, N=18) as compared to the clinical group (r=0.338, p=0.016, N=50). Conclusion: The study revealed that clinical group was significantly different in specific enzymatic activity of Cp as compared to control group. Besides this, the specific enzymatic activity of Cp was moderately but significantly correlated with serum Cu level in control group but did not reveal conclusive evidence in clinical population.