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Introduction: It has been approved that selective serotonin reuptake inhibitors (SSRIs) may exhibit anti-proliferative or cytotoxic effects on several types of cancers. The aim of the present study was to evaluate the cytotoxic effects of a newly formulated niosome of Escitalopram oxalate on a colorectal cancer cell line. Methods: The niosomes were prepared using a thin layer hydration method, resulting in particles with a size range between 150 – 450 nm and spherical morphology. Moreover, its permeability release showed 25% in 4 hours. The cytotoxicity evaluation was performed using a quantitative colorimetric MTT assay. Results: The cell viability of colon cancer cells after treatment with niosomes and pure escitalopram reduced to 28.3 ± 0.83 % and 24.07 ± 0.56%, respectively. However, the cytotoxicity assay of escitalopram-loaded niosomes suggested that the anti-proliferative effect of the niosomal formulation of escitalopram was dose and incubation time-dependent. Conclusion: These results confirm the potential of the anti-proliferative activity of escitalopram-loaded niosomes. Further application to an in vivo model is needed to study various pharmacokinetic and pharmacodynamics parameters to establish its complete therapeutic potential. [ABSTRACT FROM AUTHOR]

Introduction: Magnetic nanoparticles (MNPs) are one of the most useful particulate systems in analytical applications such as specific aptamer selection. Proteins are the most noted targets of aptamer selection. Generally, covalently immobilized protein coated MNPs are more stable structures. Methods: In this study, coagulation factor VIII (FVIII) was immobilized on MNPs. A silica coating provided isocyanate functional groups was considered to interact covalently with reactive groups of the protein, resulting in a stable protein immobilization. The reactions was run in dried toluene. At end, these MNPs were applied for affinity determination of a previously selected FVIII specific aptamers. Results: Immobilization of 1 mg FVIII (~ 3 nmol) on 5 mg particles was achieved with no significant particle aggregation. Using a fluorescence-based method, affinity measurement resulted in a calculated dissociation constant of 120 ± 5.6 nM for the FVIII-specific aptamer to the FVIII-coated MNPs. Conclusion: The final product could be a suitable protein-coated solid support for magnetic-based aptamer selection processes. [ABSTRACT FROM AUTHOR]

Background: Among diverse protein purification systems, affinity chromatography is the most attractive one in the purification process of coagulation factors. Coagulation factor VII is a plasma serine protease that has a significant role in natural human hemostasis and its recombinant form such as AryoSevenTM, has been applied in clinical treatment of bleeding disorders. Immunoaffinity chromatography is the purification method of choice that is currently applied in the development of coagulation factor VIIa products. Aptamers as nucleic acid based affinity ligands are more promising than monoclonal antibodies. In addition, DNA aptamers are more acceptable than RNA ones in this regard. Methods: In this study, two of the aptameric DNA oligonucleotides that showed acceptable affinities for purification of coagulation factor VIIa from plasma, were selected to evaluate their affinity against Aryoseven. A serial dilution of fluorescence labeled aptamers was incubated against the concentration of 1 nM from Aryoseven. Then, a fluorescence index was calculated according to the fluorescence intensity data measured from test and control samples. The dissociation constant of aptamers was calculated according to the fluorescence index using Prism5 software. Results: Results showed that the binding affinity of the 44 nucleotide aptamer was more than 81 nucleotide aptamer sequence. As a result, this aptamer could be optimized in order to develop aptamer based affinity chromatography process for this form of recombinant coagulation factor VIIa. Discussion: Aptamers with shorter length of sequence could show higher affinity in target binding, as they could adapt more easily to suitable conformation according to target interaction. However, it should be considered that the selectivity of affinity ligands is also important for target purification and analytical applications. [ABSTRACT FROM AUTHOR]

The development of enhanced drug delivery systems is one of the most attractive fields of pharmaceutical sciences, as some of the highly effective chemo/biotherapeutics for cancer treatment can not be administrated due to their high toxicities for normal cells or low stability in physiological media. However, drugs that are currently not administrable will become valuable if specific cell-targeted drug carriers can protect the normal cells from adverse effects and also improve drug pharmacokinetics. Aptamers are attractive and promising biomaterials developed with high affinity and specificity against numerous valuable targets. They could act similar to monoclonal antibodies (mAbs), and offer significant advantages. Combined with aptamers, nanostructures are smart veicles with remarkable properties for drug delivery. Combination of aptamer and nanotechnology has resulted in the production of various targeted drug delivery systems which are highly efficient in therapeutic and diagnostic applications. In this review, some of the efforts related to design and development of aptamer-targeted nanocarriers have been summarized considering: i) Aptamer importance as smart ligands and the aptamer development methods ii) Types of nanostructures combined with aptamers as targeting agent proposed in the literature iii) Cancer specific aptamers evaluated in combination with nanocarriers for diagnostic and therapeutic applications and iv) Discussion of aptamer-based smart nanocarriers according to the trend of related research works. [ABSTRACT FROM AUTHOR]

Aptamers are single stranded oligonucleotides, comparable to monoclonal antibodies (mAbs) in selectivity and affinity and have significant strategic properties in design, development and applications more than mAbs. Ease of design and development, simple chemical modification and the attachment of functional groups, easily handling and more adaptability with analytical methods, small size and adaptation with nanostructures are the valuable characteristics of aptamers in comparison to large protein based ligands. Among a broad range of targets that their specific aptamers developed, proteins and peptides have significant position according to the number of related studies performed so far. Since proteins control many of important physiological and pathological incidents in the living organisms, particularly human beings and because of the benefits of aptamers in clinical and analytical applications, aptamer related technologies in the field of proteins and peptides are under progress, exclusively. Currently, there is only one FDA approved therapeutic aptamer in the pharmaceutical market, which is specific to vascular endothelial growth factor and is prescribed for age related macular degenerative disease. Additionally, there are several aptamers in the different phases of clinical trials. Almost all of these aptamers are specific to clinically important peptide or protein targets. In addition, the application of protein specific aptamers in the design and development of targeted drug delivery systems and diagnostic biosensors is another intersting field of aptamer technology. In this review, significant efforts related to development and applications of aptamer technologies in proteins and peptides sciences were considered to emphasis on the importance of aptamers in medicinal and clinical applications. [ABSTRACT FROM AUTHOR]

Background: Celiac disease (CD) is one of the most common and chronic immune-mediated disorders of the gastrointestinal tract that affects the small intestine. Genetic factors, including human leukocyte antigen (HLA), and non-HLA genes are major risk factors in CD pathology. Moreover, environmental factors such as infections may affect CD incidence. Materials and Methods: The goal of the present study is to investigate the association between CD and viral, bacterial, fungal, and parasitic infections. Databases including Scopus, PubMed, Google Scholar, and Web of Science were searched for relevant literature until 2022. Results: Several infections have been reported to be associated with CD including reovirus, rotavirus, hepatitis B virus, influenza virus, helicobacter pylori, campylobacter jejuni, giardia lamblia, toxoplasma gondii, candida albicans, etc. Conclusion: Moreover, antibiotic administration might be a risk factor for further CD development. On the other hand, there are reports regarding the susceptibility of patients with CD to some infections, as well as protective infections against CD. Consequently, more studies are required to explain the two-sided relations between CD and infectious diseases. [ABSTRACT FROM AUTHOR]

Aptamers, or single stranded oligonucleotides, are produced by systematic evolution of ligands by exponential enrichment, abbreviated as SELEX. In the amplification and regeneration step of SELEX technique, dsDNA is conversed to ssDNA. Asymmetric PCR is one of the methods used for the generation of ssDNA. The purpose of this study was to design a random DNA library for selection of aptamers with high affinity for protein targets and develop an efficient asymmetric PCR amplification. Thus, the influence of factors including annealing temperature, number of amplification cycles, primer ratio, Mg2+ concentration and the presence of a PCR enhancer on the amplification of the desired product were evaluated. Results obtained by agarose gel electrophoresis showed that the annealing temperature of 64 °C, Mg2+ concentration of 0.25 mM, reverse to forward primer ratio of 15:1, amplification cycle of 25 and the presence L-ectoin as a PCR enhancer with the concentration of 0.4 M were the optimal conditions. Our results supported that the yield of this type of ssDNA production is sufficient for combinatorial screening of aptamers. [ABSTRACT FROM AUTHOR]

Heavy and irresponsible use of antibiotics in the last century has put selection pressure on the microbes to evolve even faster and develop more resilient strains. In the confrontation with such sometimes called "superbugs", the search for new sources of biochemical antibiotics seems to have reached the limit. In the last two decades, bioactive antimicrobial peptides (AMPs), which are polypeptide chains with less than 100 amino acids, have attracted the attention of many in the control of microbial pathogens, more than the other types of antibiotics. AMPs are groups of components involved in the immune response of many living organisms, and have come to light as new frontiers in fighting with microbes. AMPs are generally produced in minute amounts within organisms; therefore, to address the market, they have to be either produced on a large scale through recombinant DNA technology or to be synthesized via chemical methods. Here, heterologous expression of AMPs within bacterial, fungal, yeast, plants, and insect cells, and points that need to be considered towards their industrialization will be reviewed. Sources of peptide production and their applications. Some AMPs directly extracted from natural sources, some of them are chemically synthesized either using liquid or solid phase peptides synthesis, and for large scale production, recombinant expression using heterologous expression systems have been used. [ABSTRACT FROM AUTHOR]

Rapid and label-free detection of very low concentrations of biomarkers in disease diagnosis or therapeutic drug monitoring is essential to prevent disease progression in Point of Care Testing. For this purpose, we propose a multi-purpose optical Bio-Micro-Electro-Mechanical-System (BioMEMS) sensing platform which can precisely measure very small changes of biomolecules concentrations in plasma-like buffer samples. This is realized by the development of an interferometric detection method on highly sensitive MEMS transducers (cantilevers). This approach facilitates the precise analysis of the obtained results to determine the analyte type and its concentrations. Furthermore, the proposed multi-purpose platform can be used for a wide range of biological assessments in various concentration levels by the use of an appropriate bioreceptor and the control of its coating density on the cantilever surface. In this study, the present system is prepared for the identification of digoxin medication in its therapeutic window for therapeutic drug monitoring as a case study. The experimental results represent the repeatability and stability of the proposed device as well as its capability to detect the analytes in less than eight minutes for all samples. In addition, according to the experiments carried out for very low concentrations of digoxin in plasma-like buffer, the detection limit of LOD = 300 fM and the maximum sensitivity of S = 5.5 × 1012 AU/M are achieved for the implemented biosensor. The present ultrasensitive multi-purpose BioMEMS sensor can be a fully-integrated, cost-effective device to precisely analyze various biomarker concentrations for various biomedical applications. [ABSTRACT FROM AUTHOR]

Summary: Casein phosphopeptides (CPPs) are mineral‐binding bioactive peptides derived from enzymatic digestion of casein. They have been shown to increase iron bioavailability due to increasing iron solubility at the alkaline pH of the intestine. Thus, they are potentially applicable as an advantageous preparation for iron fortification of food. This study aimed to characterise a commercially available CPP and determines optimum experimental conditions for binding it with ferrous iron. The effect of three variables – pH (5–7.5), mass ratio of iron to CPP (MR) (0.04–0.16) and holding time (40–80 min) – on the CPP's iron content was investigated using the central composite design (CCD) in response surface methodology (RSM), and a quadratic model was developed. The optimisation in this survey was based on the maximum response. Among all the regression's terms, the main and quadratic effects of pH represented the most significant influences on the iron content (P‐value <0.05). The obtained optimum conditions were as follows: pH 6.5, MR 0.14 and holding time 72 min, resulting in binding 68.66 mg iron per gram of the CPP. The quantity of iron bound to the CPP depended considerably on the experimental conditions and proved the importance of optimisation. [ABSTRACT FROM AUTHOR]

Background: In the pharmaceutical industry, hard- and soft-shelled capsules are typically made from gelatin, commonly derived from bovine and porcine sources. To ensure that pharmaceutical products comply with halal regulations in Muslim countries (no porcine products allowed), development of a valid, reliable, quick, and most importantly, cost-effective tests are of utmost importance. Methods: We developed a species-specific duplex polymerase chain reaction (PCR) assay targeting 149 bp porcine and 271 bp bovine mitochondrial DNA (mtDNA) to simultaneously detect both porcine and bovine DNA (in one reaction at the same time) in gelatin. Some additional simplex PCR tests (targeting 126 bp bovine and 212 bp porcine mtDNA) and real-time PCR using a commercially available kit (for identification of porcine DNA) were used to verify the selectivity and sensitivity of our duplex PCR. After optimization of DNA extraction and PCR methods, hard/soft pharmaceutical gelatin capsules (containing drug) were tested for the presence of porcine and/or bovine DNA. Results: Duplex PCR detected the presence of as little as 0.1% porcine DNA, which was more accurate than the commercially available kit. Of all gelatin capsules tested (n = 24), 50% contained porcine DNA (pure porcine gelatin alone or in combination with bovine gelatin). Conclusions: Duplex PCR presents an easy-to-follow, quick, low-cost and reliable method to simultaneously detect porcine and bovine DNAs (>100 bp) in minute amounts in highly processed gelatin-containing pharmaceutical products (with a 0.1% sensitivity for porcine DNA) which may be used for halal authentication [ABSTRACT FROM AUTHOR]

[Display omitted] • Antimicrobial peptides (AMPs) can have antibacterial, antifungal, antiviral and anti-inflammatory activities. • Net charge, hydrophobicity, and amino acid sequence can affect AMPs function. • Modification with other functional groups can also influence the AMPs activities. Proteins and peptides, as polypeptide chains, have usually got unique conformational structures for effective biological activity. Antimicrobial peptides (AMPs) are a group of bioactive peptides, which have been increasingly studied during recent years for their promising antibacterial, antifungal, antiviral and anti-inflammatory activity, as well as, other esteemed bioactivities. Numerous AMPs have been separated from a wide range of natural resources, or produced in vitro through chemical synthesis and recombinant protein expression. Natural AMPs have had limited clinical application due to several drawbacks, such as their short half-life due to protease degradation, lack of activity at physiological salt concentrations, toxicity to mammalian cells, and the absence of suitable methods of delivery for the AMPs that are targeted and sustained. The creation of synthetic analogs of AMPs would both avoid the drawbacks of the natural analogs and maintain or even increase the antimicrobial effectiveness. The structure–activity relationship of discovered AMPs or their derivatives facilitates the development of synthetic AMPs. This review discovered that the relationship between the activity of AMPs and their positive net charge, hydrophobicity, and amino acid sequence and the relationship between AMPs' function and other features like their topology, glycosylation, and halogenation. [ABSTRACT FROM AUTHOR]

A quantitative structure activity relationship analysis has been applied to a data set of 20 N-phenyl-N′-(4-pyridinyl)-urea derivatives with anticonvulsant activity. Semi-empirical quantum chemical calculations at AM1 level was used to find the optimum 3D geometry of the studied molecules. Four types of molecular descriptors including classical (substituent constants), constitutional, topological and quantum chemical was used to derive a quantitative relationship between the anticonvulsant activity and structural properties. A multi-parametric equation containing three descriptors with good statistical qualities was obtained using multiple linear regression (MLR). In addition, partial least squares (PLS) regression was used to model the structure-activity relationships, more accurately. The results confirmed the superiority of the results obtained by PLS relative to MLR. The respective percent relative errors of prediction for the MLR and PLS regression methods was between (-3.18)–(+3.15) and (-1.28)–(+1.52). [Copyright &y& Elsevier]

Feature extraction is one of the most important preprocessing steps in predicting the interactions between RNAs and proteins by applying machine learning approaches. Despite many efforts in this area, still, no suitable structural feature extraction tool has been designed. Therefore, an online toolbox, named RPINBASE which can be applied to different scopes of biological applications, is introduced in this paper. This toolbox employs efficient nested queries that enhance the speed of the requests and produces desired features in the form of positive and negative samples. To show the capabilities of the proposed toolbox, the developed toolbox was investigated in the aptamer design problem, and the obtained results are discussed. RPINBASE is an online toolbox and is accessible at http://rpinbase.com. • Generating queryable positive samples from PDB complexes • Generating queryable artificial proposed negative samples (based on family and clan) • Providing a wide range of extracted features for primary and secondary structures of RNA and protein macromolecules. • Selecting efficient and high performance dataset powered by preprocessed and stored data to download feature vectors quickly. • Possibility of sample filtering by PDB information and structural features of macromolecules. [ABSTRACT FROM AUTHOR]

Today, the treatment of bacterial infections is a major challenge, due to growing rate of multidrug-resistant bacteria, complication of treatment and increased healthcare costs. Moreover, new treatments for bacterial infections are limited. Oligonucleotide aptamers are single stranded DNAs or RNAs with target-selective high-affinity feature, which considered as nucleic acid-based affinity ligands, replacing monoclonal antibodies. The aptamer-based systems have been found to be talented tools in the treatment of microbial infections, regarding their promising anti-biofilm and antimicrobial activities; they can reduce or inhibit the effects of bacterial toxins, and inhibit pathogen invasion to immune cell, as well as they can be used in drug delivery systems. The focus of this review is on the therapeutic applications of aptamers in infections. In this regard, an introduction of infections and related challenges were presented, first. Then, aptamer definition and selection, with a brief history of aptamers development against various pathogens and toxins were reviewed. Diverse strategies of aptamer application in drug delivery, as well as, the effect of aptamers on the immune system, as the main natural agents of human defense against pathogens, were also discussed. Finally, the future trends in clinical applications of this technology were discussed. [ABSTRACT FROM AUTHOR]

The "bispecifics" market improved over the past decade due to the development of many technological platforms including bispecific T cell engagers (BiTEs). The approval of blinatumomab, the most advanced bispecific T-cell engager (BiTE) in clinical trials, can be a significant milestone in the development of bispecific antibodies. Both Chinese hamster ovary (CHO) cells and E. coli strain are considered as the most widely used hosts for the large-scale production of therapeutic monoclonal antibodies. Since both of the economic and qualitative aspects of protein production are important in industry, selection of a suitable protein expression system is very critical. The BsAb gene was cloned into the expression vectors FC550A-1, pcDNA3.1 (+), and PET22b and 6 × His-tagged BsAb then purified on a Ni-NTA chromatography column. Both SDS-PAGE and Western blotting analysis of the purified protein demonstrated that blinatumomab was successfully expressed as a 55 kDa in both expression systems. The antigen-binding properties of blinatumomab were compared in the mammalian system versus Escherichia coli. The results showed that the purified antibody from a mammalian expression system has better binding activity than the one from E. coli host. [ABSTRACT FROM AUTHOR]

miRNAs as one of the potential therapeutic agents have been recently considered for cancer treatment. AS1411 (aptNCL) is a DNA aptamer specifically binding to nucleolin protein on the cancer cell surface with antiproliferative effect. The aim of the study was to develop a conjugate consisting of aptNCL (as targeted delivery of therapeutic agent) and miRNA let-7d (as a tumor suppressor) using two different linking methods and also to evaluate the potential effect of the conjugates on the proliferation of gastric cancer (MKN-45) cell line compared to negative control cell line of human dermal fibroblast (HDF). Conjugation was performed covalently by SM (PEG)2 as a bifunctional crosslinker (conjugate-1) and noncovalently, using 19bp complementary sticky end sequences (conjugate-2). Nucleolin positive MKN-45 and nucleolin negative HDF cells were cultured and treated with the conjugates. Then, the changes in let-7d expression and cell proliferation were determined using Real-time PCR and MTT methods, respectively. In MKN-45 cells, the conjugates caused significant increase in let7-d uptake compared with HDF cells (P = 0.0001). The conjugate-1, likely due to its higher stability compared with the conjugate-2, led to significantly more increase in intracellular let-7d in MKN-45 cells (30 fold versus 15 fold, respectively, P = 0.0001). The conjugates revealed more potent antiproliferative effect against gastric cancer cells compared with aptNCL alone (P = 0.0001). It was found that the aptNCL-let-7d conjugate efficiently carried let-7d into the cancer cells. Also, it appears that in the setting of aptNCL-let-7d conjugate, let-7d and aptNCL moieties could cooperate and synergistically exhibit the antiproliferative effect on cancer cells. [ABSTRACT FROM AUTHOR]

Abstract: DNAzyme and aptamer conjugations have already been used for sensitive and accurate detection of several molecules. In this study, we tested the relationship between conjugation orientation of DNAzyme and aflatoxin B1 aptamer and their subsequent peroxidase activity. Circular dichroism (CD) spectroscopy and biochemical analysis were used here to differentiate between these two conjugation patterns. Results showed that DNAzyme–aptamer has more catalytic activity and efficiency than aptamer–DNAzyme. Thereby, DNAzyme–aptamer with its superior efficiency can be used for design and development of more sensitive aflatoxin B1 DNA based biosensors. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are one of the most important origins of cancer progression and metastasis. CSCs have unique self-renewal properties and diverse cell membrane receptors that induced the resistance to the conventional chemotherapeutic agents. Therefore, the therapeutic removal of CSCs could result in the cancer cure with lack of recurrence and metastasis. In this regard, targeting CSCs in accordance to their specific biomarkers is a talented attitude in cancer therapy. Various CSCs surface biomarkers have been described, which some of them exhibited similarities on different cancer cell types, while the others are cancer specific and have just been reported on one or a few types of cancers. In this review, the importance of CSCs in cancer development and therapeutic response has been stated. Different CSCs cluster of differentiation (CD) biomarkers and their specific function and applications in the treatment of cancers have been discussed, Special attention has been made on targeted nano-delivery systems. In this regard, several examples have been illustrated concerning specific natural and artificial ligands against CSCs CD biomarkers that could be decorated on various nanoparticulated drug delivery systems to enhance therapeutic index of chemotherapeutic agents or anticancer gene therapy. The outlook of CSCs biomarkers discovery and therapeutic/diagnostic applications was discussed. [ABSTRACT FROM AUTHOR]

Combination of aptamers with DNAzymes attracted intense attention for development of DNA-based biosensors for detection of mycotoxins. In the present study a combination of aflatoxin B1 specific aptamer and HRP- (horseradish peroxidase-) mimicking DNAzyme was optimized for detecting aflatoxin B1. Detecting approach is based on the binding affinity of aflatoxin B1 to its specific aptamer and conversion of substrate to a detectable colorimetric signal by a linked DNAzyme. Compared to conventional methods for aflatoxin B1 detection, DNA-based assay has the advantages of low cost, long-term stability, and rapid, simple, and user-friendly steps. [ABSTRACT FROM AUTHOR]

Protein specific aptamers are highly applicable affinity ligands in different fields of research and clinical applications. They have been developed against various targets, in particular, biomacromolecules such as proteins. Among human proteins, the coagulation factors are the most attractive targets for aptamer selection and their specific aptamers have valuable characteristics in therapeutic and analytical applications. In this study, a plasma derived coagulation factor VIII was considered as the protein target for DNA aptamer selection using size exclusion chromatography-SELEX. Potential aptameric oligonucleotides with high affinity and specificity were achieved during eight rounds of selection. Binding affinity constant of selected aptamer and aptameric enriched pool were in nanomolar range that was comparable to monoclonal antibodies. Further improvement studies can result in aptamers that are more promising as an industrial affinity ligand for the purification of anti-hemophilia factor from plasma source. [ABSTRACT FROM AUTHOR]

Some antimicrobial peptides have been shown to be able to inhibit the proliferation of cancer cell lines. Various strategies for treating cancers with active peptides have been pursued. According to the reports, anticancer peptides are important therapeutic peptides, which can act through two distinct pathways: they either just create pores in the cell membrane, or they have a vital intracellular target. In this review, publications up to Sep. 2021 had extracted form Scopus and PubMed using "antimicrobial peptide" and "anticancer peptide" as keywords. In second step, "computational design" related publications extracted. Among publications, those have similar scopes were classified and selected based on mechanisms of action and application. In this review, the most recent advances in the field of antimicrobial peptides with anti-cancer activities have been summarized. Freely available webservers such as AntiCP, ACPP, iACP, iACP-GAEnsC, ACPred are discussed here. In conclusion, despite some limitations of ACPs such as production cost and challenges, short half-life and toxicity on normal cells, the beneficial properties of AMPs make some of them good therapeutic agents for cancer therapy. Towards designing novel ACPs, the computational methods have substantial position and have been used progressively, today. [Display omitted] • Antimicrobial peptides can also have anti-cancer activities named anti-cancer peptides (ACPs). • Pore formation, cell-penetration and tumor targeting are the main mechanisms of ACPs. • The computational methods have substantial position in ACP design. • AntiCP, ACPP, iACP, iACP-GAEnsC, ACPred are some of available webservers for ACP prediction. [ABSTRACT FROM AUTHOR]

Voltage-dependent calcium channels are crucial targets for a wide range of clinically active pharmacological agents. From these agents, 1,4-dihydropyridines constitute a group of small organic compounds are based on a core pyridine structure which can both block and enhance calcium currents. They are considered specific for L-Type calcium channels; however, other channel types, and in particular certain T-Type channels, may show sensitivity to dihydropyridine compounds. In this study, we synthesized a novel group of bis-1,4-dihydropyridines using the procedure reported by Dagnino that involved the condensation of n-alkyl diacetoacetate ( n = 2–7) with methyl-3-aminocrotonate and nitrophenylaldehyde. The synthesis was run under two conditions: (i) reflux and (ii) microwave. Calcium channels antagonist activity were determined in vitro using guinea-pig ileum longitudinal smooth muscle assay. Synthesis of these compounds was confirmed with 1H-NMR, IR and mass spectrometry. Then IC50 of them are calculated and compared with Nifedipine. Finally, the result of this pharmacological assay was used in quantitative structure–activity relationship studies utilizing multiple linear regression analysis. Most of these compounds are less active compared with Nifedipine. Decrease in activity is the result of increase in steric hindrance. The quantitative structure–activity relationship study indicates that the activity is related to the electrostatic and topological parameters and the distance between two C5-esteric groups of 1,4-dihydropyridine rings. [ABSTRACT FROM AUTHOR]

Peptides are oligomers of amino acids, which have been used in a wide range of applications, particularly in medical and pharmaceutical sciences. Linear peptides have been extensively developed in various fields of medicine as therapeutics or targeting agents. The branched structure of peptide dendrimers with peptide (commonly, poly l ‑Lysine) or non-peptide (commonly poly‑amidoamine) core, often exhibits valuable novel features, improves stability and enhances the functionality of peptide in comparison with small linear peptides. The potential applications of Branched and hyper-branched peptidic structures which are known as peptide dendrimers in biomedical sciences have been approved vastly. A peptide dendrimer contains three distinct parts including core, building blocks and branching units or surface functional groups. These structures provide a lot of opportunities in the pharmaceutical field, particularly for novel drug development. In this review, a brief summary of different biomedical applications of peptide dendrimers is presented, and peptide dendrimers as active pharmaceutical ingredients and drug delivery carriers are discussed. Applications of peptide dendrimers in vaccines and diagnostic tools are also presented, in brief. Generally, peptide dendrimers are promising biomaterials with high evolution rate for clinical and non-clinical applications in medicine. Unlabelled Image [ABSTRACT FROM AUTHOR]