Combinatorial Chemistry & High Throughput Screening - Volume 22, Issue 2, 2019

Background: Molecularly Imprinted Polymers (MIPs), a type of biomimetic materials have attracted considerable interest owing to their cost-effectiveness, good physiochemical stability, favorable specificity and selectivity for target analytes, and long shelf life. These materials are able to mimic natural recognition entities, including biological receptors and antibodies, providing a versatile platform to achieve the desirable functionality for various biomedical applications. Objective: In this review article, we introduce the most recent development of MIPs to date. We first highlight the advantages of using MIPs for a broad range of biomedical applications. We then review their various methods of synthesis along with their latest progress in biomedical applications, including biosensing, drug delivery, cell imaging and drug discovery. Lastly, the existing challenges and future perspectives of MIPs for biomedical applications are briefly discussed. Conclusion: We envision that MIPs may be used as potential materials for diverse biomedical applications in the near future.

Background: With the increasing resistance and side effects caused due to antifungal agents there is an urgent need for the new potent antifungal agents with low toxicity profile. Imidazoles have been used against fungal infections since long time. Further, our previous studies demonstrated that mercaptoimidazoles possessed good antifungal potency. Aim and Objective: This study was aimed to study the antifungal potency of new series of 2- mercaptoimidazoles. Materials and Methods: Eighteen new 2-mercaptoimidazoles containing substituted phenyl group were synthesized and structures of the synthesized compounds were characterized by spectral studies. The synthesized compounds were screened for their antifungal potency. Compound 2-(1-(3-hydroxyphenyl)-2- mercapto-1H-imidazol-4-yl)phenol was found to be the most potent compound among all synthesized compounds against tested fungal strains. Moreover, all the synthesized compounds were further subjected to molecular docking study for the inhibition of enzyme 14α-demethylase. Results: The in-silico molecular docking study results showed that all the synthesized compounds have minimum binding energy and good affinity for the active site and may be considered as good inhibitor of 14α-demethylase. Conclusion: 2-mercaptoimidazoles may be used as potential lead molecules as 14α-demethylase inhibitors.

Background: A set of β-lactam antibiotics, aminoglycoside antibiotics, and tetracycline antibiotics were proposed and analyzed with the use of Quantitative Structure-Activity Relationships (QSAR) method. Objective: The characterization of selected antimicrobial compounds in terms of both physicochemical and pharmacological on the basis of calculations of quantum mechanics and possessed biological activity data. Methods: During the study, Multiple Linear Regression (MLR) supported with Factor Analysis (FA) and Principal Component Analysis (PCA) was made, as the types of proposed chemometric approach; the semi-empirical level of in silico molecular modeling was used for calculations and comparison of molecular descriptors both in a vacuum and in the aquatic environment. Results: The relationships between structure and microbiological activity enabled the characterization and description of the analyzed molecules using statistically significant descriptors belonging in most cases to different structural, geometric and electronic elements defining at the same time the properties of the studied three different classes of examined antibiotics. Conclusion: The chemometric methods used revealed the influence of some of the elements of structures examined molecules belonging to main antibiotics classes and responsible for the antimicrobial activity.

Background: Adenosine deaminase (ADA) is an important enzyme in purine metabolism and is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Traditional Chinese Herbal Medicine (TCHM) is widely used alone or in combination with chemotherapy to treat cancer, due to its ability to deliver a broad variety of bioactive secondary metabolites as promising sources of novel organic natural agents. Objective: In the present study, 29 varieties of medicinal plants were screened for the presence of ADA inhibitors. Results: Extracts from Reynoutria japonica, Glycyrrhiza uralensis, Lithospermum erythrorhizon, Magnolia officinalis, Gardenia jasminoides, Stephania tetrandra, Commiphora myrrha, Raphanus sativus and Corydalis yanhusuo demonstrated strong ADA inhibition with rates greater than 50%. However, Reynoutria japonica possessed the highest ADA inhibitory activity at 95.26% and so was used in our study for isolating the ADA inhibitor to be further studied. Eight compounds were obtained and their structures were identified. The compound H1 had strong ADA inhibitory activity and was deduced to be emodin by 1H and 13C-NMR spectroscopic analysis with an IC50 of 0.629 mM. The molecular docking data showed that emodin could bind tightly to the active site of ADA. Our results demonstrated that emodin displayed a new biological activity which is ADA inhibitory activity with high cytotoxic activity against K562 leukemia cells. The bioactivity of cordycepin was significantly increased when used in combination with emodin. Conclusion: Emodin may represent a good candidate anti-cancer therapy and adenosine protective agent.

Background: In this study, we developed a convenient methodology for the synthesis of coumarin linked to pyrazolines and pyrano [2,3-h] coumarins linked to 3-(1,5-diphenyl-4,5- dihydro-1H-pyrazol-3-yl)-chromen-2-one derivatives using Chlorosulfonic acid supported Piperidine-4-carboxylic acid (PPCA) functionalized Fe3O4 nanoparticles (Fe3O4-PPCA) catalyst. Materials and Methods: Fe3O4-PPCA was investigated as an efficient and magnetically recoverable Nanocatalyst for the one-pot synthesis of substituted coumarins from the reaction of coumarin with a variety of aromatic aldehydes in high to excellent yield at room temperature under solvent-free conditions. The magnetic nanocatalyst can be easily recovered by applying an external magnet device and reused for at least 10 reaction runs without considerable loss of reactivity. Results and Conclusion: The advantages of this protocol are the use of commercially available materials, simple and an inexpensive procedure, easy separation, and an eco-friendly procedure, and it shows good reaction times, good to high yields, inexpensive and practicability procedure, and high efficiency.

Background: Although liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is preferred as a reliable method, some molecules in the blood matrix may lead to false positive or false negative results. False positive or negative results show the direction of the deviation rate from the target value. Aim: The aim of this study was to investigate the effect of seven different radiopaque agents on four immunosuppressant drugs. Methods: Every agent coded with RM1 to RM7 was added to control materials containing tacrolimus, everolimus, sirolimus, and cyclosporine A drugs. Measurements were performed using an LC-MS/MS instrument. Bias values were calculated to detect the deviation rates. Results: All RMs led to false negative results in the tacrolimus and cyclosporine A levels at a rate of -19.77% (95% CI, -27.16 to 12.52) to -44.45% (95% CI, -49.20 to -39.69). The smallest deviations were seen in the everolimus levels with the administration of RM6 (gadodiamide) and in the sirolimus levels with RM1 (gadobutrol) at the rates of 4.04% (95% CI, -11.36 to -3.17) and 2.11% (95% CI, -7.18 to 7.11), respectively. The most affected drug by RM4 (gadopentetate dimeglumine salt) was sirolimus at the rate of 114.01% (95% CI, 97.31 - 130.76). RM5 (gadodiamide) interfered cyclosporine A at the most. The highest deviations were observed with the administration of RM3 (iohexol) in the everolimus and sirolimus levels at the rates of 153.72% (95% CI, 142.44 to 164.78) and 171.41% (95% CI, 157.91 to 184.97), respectively. Conclusion: Radiopaque agents interfered the measurement of immunosuppressant drugs. Especially, everolimus and sirolimus levels were affected due to using iohexol. The choice of gadodiamide or ioversol is important to reduce the risk of interference for everolimus measurement. The blood samples should be obtained for measurement of drug levels before contrast-enhanced imaging.

Background: Riboswitches are cis-acting, non-coding RNA elements found in the 5’UTR of bacterial mRNA and 3’ UTR of eukaryotic mRNA, that fold in a complex manner to act as receptors for specific metabolites hence altering their conformation in response to the change in concentrations of a ligand or metabolite. Riboswitches function as gene regulators in numerous bacteria, archaea, fungi, algae and plants. Aim and Objective: This study identifies different classes of riboswitches in the Archaeal domain of life. Previous studies have suggested that riboswitches carry a conserved aptameric domain in different domains of life. Since Archaea are considered to be the most idiosyncratic organisms it was interesting to look for the conservation pattern of riboswitches in these obviously strange microorganisms. Materials and Methods: Completely sequenced Archaeal Genomes present in the NCBI repository were used for studying riboswitches and other ncRNAs. The sequence files in FASTA format were downloaded from NCBI Genome database and information related to these genomes was retrieved from GenBank. Three bioinformatics approaches were used namely, ab initio, consensus structure prediction and statistical model-based prediction for identifying riboswitches. Results: Archaeal genomes have a sporadic distribution of putative riboswitches like the TPP, FMN, Guanidine, Lysine and c-di-AMP riboswitches, which are known to occur in bacteria. Also, a class of riboswitch sensing c-di-GMP, a second messenger, has been identified in a few Archaeal organisms. Conclusion: This study clearly reveals that bioinformatics methods are likely to play a major role in identifying conserved riboswitches and in establishing how widespread these classes are in all domains of life, even though the final confirmation may come from wet lab methods.