Current drug discovery technologies最新文献

Background: The viral thymidine kinase (TK) phosphorylates the antiviral medication famciclovir (FCV), which treats herpes simplex virus (HSV-TK). The phosphorylated FCV destroys the infected cells by preventing cellular DNA synthesis.

Objective: We hypothesize that FCV impurity, which is a related substance to FCV, should be efficient in killing cells independent of HSV-TK and is currently the most widely used suicide agent for gene therapy of cancer.

Methods: This study proposes the binding affinity of these derivatives for the active site of TK through molecular docking to a protein (PDB ID: 1W4R). The derivatives' reliability was ensured through the in-silico preliminary drug designing model by screening their Lipinski rule of five violations, if any, ADMET prediction for their profile using online tools. Using MOE 2009.10 computational software, we performed molecular docking of approximately 22 famciclovir derivatives alongside the famciclovir drug.

Results: Our results suggest that these derivatives are indicative of possible chemical stability irrespective of all the parameters used to evaluate the selected derivatives as a possible drug candidates for their cytotoxicity. FC20 (i.e., 2-(2-(2-((1-(9-(4-Acetoxy-3-(acetoxymethyl)butyl)-2-amino-9Hpurin- 8-yl)ethyl)amino)-9H-purin-9-yl)ethyl)propane-1,3-diyl diacetate) and FC21 (i.e., 2-Amino-1,9- dihydro-9-(4-hydroxybutyl)-6H-purin-6-one), showed maximum and minimum scores of -26.95 and - 7.21 kcal/mol, respectively when compared to famciclovir (-15.4122 kcal/mol).

Conclusion: Considering that there might be a cytotoxicity effect due to competition between protein TK and the suicidal gene of famciclovir derivatives. The outcome of the study proved that the FCV impurity could successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug. Further, it can be used for the design and development of novel compounds of FCV impurity that could be cytotoxic agents if properly delivered to cancer cells.

Background: Candidiasis is a serious problem in women's health that is caused by Candida species, especially Candida albicans. In this study, the effect of carotenoids in carrot extracts on Candida species including Candida albicans ATCC1677, Candida glabrata CBS2175, Candida parapsilosis ATCC2195, and Candida tropicalis CBS94 was investigated.

Methods: In this descriptive study, the carrot plant was prepared from a carrot planting site in December 2012, and then the characteristics of the plant were determined. After extracting carotenoids from carrots, the susceptibility of different Candida species to carotenoids in carrot extract was determined. Also, the minimum inhibitory concentration and the minimum lethal concentration of the extracts were measured by the macro-dilution method. Finally, the data were analyzed by SPSS software using the Kruskal-Wallis test and Mann-Whitney post-hoc test with Bonferroni adjustment.

Results: The highest growth inhibition zone was obtained for carrot extract at a concentration of 500 mg/ml for C. glabrata and C. tropicalis. The MFC of carrot extract on Candida species was 62.5 mg/ml for C. albicans, C. glabrata, and C. parapsilosis, and 125 mg/ml for C. tropicalis. The MFC of carrot extract on Candida species was 125 mg/ml for C. albicans, C. glabrata, and C. parapsilosis, and 250 mg/ml for C. tropicalis.

Conclusion: The present study can be the starting point for research activities in this direction and promises new therapies based on the use of carotenoids.

Background: The frequency of observed invasive Aspergillosis has increased in recent years. Infection with other molds happens but does not lead to a large proportion of invasive infections. The present study aims to isolate Bacillus amyloliquefaciens M13-RW0 from soil and evaluate its antifungal effects against some saprophytic fungi, such as Aspergillus niger, Aspergillus flavus, and Mucor hiemalis.

Materials and methods: In this research, a total of 150 samples (from the soil, air, and surfaces) were prepared from different parts of Isfahan, Iran. Isolation and purification of growing bacteria were conducted using the nutrient agar medium. The inhibitory effects of 100 isolated bacteria were evaluated against the growth of A. niger, A. flavus, and M. hiemalis, 4 bacteria were isolated with inhibitory effects against the selected fungi, and consequently, one of the bacteria isolated from the soil samples was found to show the highest inhibition of fungal growth. Quantitative evaluation of the growth inhibitory effect was performed using linear culturing of fungal suspension (10⁴ spore/ml) at distances of 5, 10, 15, 20, 25, and 30mm from bacterial isolate (0.5 McFarland) on Sabouraud Dextrose Agar (SDA) medium. Results were checked 24, 48, 72, and 96 hours later. The bacterial isolate with the most inhibitory effect was identified by phenotypic and molecular tests.

Results: According to the results, among the 4 inhibitory bacterial isolates, Bacillus amyloliquefaciens strain M13-RW01, isolated from the soil samples, was identified as the bacterium with the most significant potential antifungal activity. The strong inhibitory effect was revealed after 48 hours for all distances of 15mm and more between the fungi and the bacterium.

Conclusion: The identified bacterium could not only be considered an inhibitor bacterium against saprophytic fungi but could also be put forward to help produce new antifungal drugs for controlling fungal diseases.

Background: Diabetes occurs due to insulin deficiency or less insulin. To manage this condition, insulin administration as well as increased insulin sensitivity is required, but exogeneous insulin cannot replace the sensitive and gentle regulation of blood glucose levels same as β cells of healthy individuals. By considering the ability of regeneration and differentiation of stem cells, the current study planned to evaluate the effect of metformin preconditioned buccal fat pad (BFP) derived mesenchymal stem cells (MSCs) on streptozotocin (STZ) induced diabetes mellitus in Wistar rats.

Materials & methods: The disease condition was established by using a diabetes-inducing agent STZ in Wistar rats. Then, the animals were grouped into disease control, blank, and test groups. Only the test group received the metformin-preconditioned cells. The total study period for this experiment was 33 days. During this period, the animals were monitored for blood glucose level, body weight, and food-water intake twice a week. At the end of 33 days, the biochemical estimations for serum insulin level and pancreatic insulin level were performed. Also, histopathology of the pancreas, liver and skeletal muscle was performed.

Results: The test groups showed a decline in the blood glucose level and an increase in the serum pancreatic insulin level as compared to the disease group. No significant change in food and water intake was observed within the three groups, while body weight was significantly reduced in the test group when compared with the blank group, but the life span was increased when compared with the disease group.

Conclusion: In the present study, we concluded that metformin preconditioned buccal fat pad-derived mesenchymal stem cells have the ability to regenerate damaged pancreatic β cells and have antidiabetic activity, and this therapy is a better choice for future research.

Background: Antipsychotics interfere with virtually all hallmarks of cancer, including angiogenesis. Vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth receptors (PDGFRs) play crucial roles in angiogenesis and represent targets of many anti-cancer agents. We assessed and compared the binding effects of antipsychotics and receptor tyrosine kinase inhibitors (RTKIs) on VEGFR2 and PDGFRα.

Methods: FDA-approved antipsychotics and RTKIs were retrieved from DrugBank. VEGFR2 and PDGFRα structures were obtained from Protein Data Bank and loaded on Biovia Discovery Studio software to remove nonstandard molecules. Molecular docking was carried out using PyRx and CBDock to determine the binding affinities of protein-ligand complexes.

Results: Risperidone exerted the highest binding effect on PDGFRα (-11.0 Kcal/mol) as compared to other antipsychotic drugs and RTKIs. Risperidone also demonstrated a stronger binding effect on VEGFR2 (-9.6 Kcal/mol) than the RTKIs, pazopanib (-8.7 Kcal/mol), axitinib (-9.3 Kcal/mol), vandetanib (-8.3 Kcal/mol), lenvatinib ( -7.6 Kcal/mol) and sunitinib (-8.3 Kcal/mol). Sorafenib (an RTKI), however, exhibited the highest VEGFR2 binding affinity of -11.7 Kcal/mol.

Conclusion: Risperidone's superior binding affinity with PDGFRα when compared to all reference RTKIs and antipsychotic drugs, as well as its stronger binding effect on VEGFR2 over the RTKIs, sunitinib, pazopanib, axitinib, vandetanib, and lenvatinib, imply that it could be repurposed to inhibit angiogenic pathways and subjected to pre-clinical and clinical trials for cancer therapy.

Background: Hypothyroidism is a common endocrine disease in the world that causes morbidity and mortality due to its association with metabolic diseases, especially in old age, and longterm treatment with levothyroxine causes many side effects for patients. Treatment with herbal medicine can regulate thyroid hormones and prevent side effects.

Objective: The purpose of this systematic review is the evaluation of the effect of herbal medicine on the signs and symptoms of primary hypothyroidism.

Methods: PubMed, Embase, Google Scholar, Scopus, and Cochrane Central Register of Controlled Trials were searched until 4 May, 2021. We selected randomized clinical trials (RCTs) that have assessed the effect of herbal medicine on hypothyroidism.

Results: Out of 771 articles, 4 trials with 186 participants were included. In one study, Nigella sativa L. caused a significant decrease in weight (P=0.004) and body mass index (BMI) (P=0.002). TSH levels were reported to be decreased and T3 increased in the treatment group (P =0.03) (P=0.008), respectively. In another study on Nigella sativa L., results did not show a significant difference between the two groups (p=0.02). A significant decrease in total cholesterol (CHL) and fasting blood sugar (FBS) was reported in participants with negative anti-thyroid peroxidase (anti-TPO) antibodies. In patients with positive anti-TPO antibodies, a significant increase in total cholesterol and FBS was observed in the intervention group (p=0.02). In the third RCT, T3 in the ashwagandha group at 4 and 8 weeks significantly increased by 18.6% (p=0.012) and 41.5% (p < 0.001), respectively. A noticeable increase was found in the T4 level from baseline by 9.3% (p= 0.002) and 19.6% (p < 0.001) at 4 and 8 weeks, respectively. TSH levels fell remarkably in the intervention group compared to placebo at 4 weeks (p <0.001) and 8 weeks (p <0.001), respectively. In the last article selected, Mentha x Piperita L. showed no significant difference in fatigue scores between intervention and control groups at the midpoint (day 7), while fatigue scores improved in the intervention group in all subscales compared to the control group on day 14.

Conclusion: Some herbal remedies, including Nigella sativa L., ashwagandha, and Mentha x Piperita L., can improve the signs and symptoms of primary hypothyroidism, but using a more extensive and advanced methodology will provide us with more complete results.

More than two hundred years ago, taurine was first isolated from materials derived from animals. It is abundantly found in a wide range of mammalian and non-mammalian tissues and diverse environments. Taurine was discovered to be a by-product of the metabolism of sulfur only a little over a century and a half ago. Recently, there has been a renewed academic interest in researching and exploring various uses of the amino acid taurine, and recent research has indicated that it may be useful in the treatment of a variety of disorders, including seizures, high blood pressure, cardiac infarction, neurodegeneration, and diabetes. Taurine is currently authorised for the therapy of congestive heart failure in Japan, and it has shown promising results in the management of several other illnesses as well. Moreover, it was found to be effective in some clinical trials, and hence it was patented for the same. This review compiles the research data that supports the prospective usage of taurine as an antibacterial, antioxidant, anti-inflammatory, diabetic, retinal protective, and membrane stabilizing agent, amongst other applications.

Spirulina or Arthrospira, a Cyanobacterium from the class Cyanophyceae, with a wide range of properties, has been applied for over 400 years. The present study aimed to review available investigations surrounding the clinical and pharmacological properties of Spirulina that have been carried out so far. Databases including Scopus, PubMed, Google Scholar, and Web of Science were searched for relevant literature using the keywords: (Spirulina), (pharmacology), and (clinical). About 130 papers that studied the pharmacological characteristics of Spirulina in animal models, as well as clinical trials, were selected from the beginning to 29 July 2021. According to this review, antioxidative, anti-inflammatory, anti-neoplastic, hypolipidemic, antiviral, immunomodulatory, antimicrobial, anti-atherogenic, anti-diabetic, and radio-protective functions are attributed to Spirulina. Moreover, Spirulina's positive influence on several organs, including hair, skin, liver, CNS, lung, and genitourinary tract, are ascribed to different components of various species of Spirulina such as Spirulina platensis, Spirulina fusiformis, and Spirulina maxima. Although so many studies have been accomplished on every aspect of Spirulina in recent years, the lack of a comprehensive investigation surrounding this microalga encouraged us to prepare this paper. Therefore, the present study could be considered an up-to-date overview of the clinical, pharmacological, and molecular aspects of Spirulina, resulting in more occupational research on this valuable organism.

Background: In this study, zinc oxide nanoparticles (ZnO-NPs) were biologically synthesized from Abelmoschus esculentus L. (Okra) mucilage fraction (OM).

Methods: Analytical techniques were employed to study the formation and properties of OM-ZnO NPs, including their morphology, shape, size distribution, and surface charges. Additionally, OM-ZnO NPs were assessed for their antimicrobial, antioxidant, and cytotoxic properties.

Results: UV-visible spectroscopy confirmed the formation of OM-ZnO NPs, evident by the appearance of an SPR peak at 368.8 nm. The FTIR spectroscopy demonstrated that OM functional groups contribute to the formation and stability of the NPs. Micrographs from TEM and SEM showed that OM-ZnO NPs ranged from 15-40 nm in diameter, whereas hydrodynamic diameter and surface charge values obtained from Zeta and DLS were 72.8 nm and 14.6 mv, respectively. XRD analysis indicated the OM-ZnO NPs were crystalline with a wurtzite structure and a crystallite size of 27.3 nm, while EDX revealed a zinc: oxygen ratio of 67.5:34. Further, the OM-ZnO NPs demonstrated significant antimicrobial activity in response to different types of bacteria. In the antioxidant assay, the OM-ZnO NPs scavenged DPPH with 68.6% of the efficiency of ascorbic acid (100%).

Conclusion: The present study demonstrated the cytotoxic efficacy of MO-ZnO NPs against MCF7 cells with an IC50 of 43.99 μg/ml. Overall, the green synthesis of ZnO NPs by OM was successful for many biological applications, such as antimicrobial, antioxidant, and anticancer. Moreover, OM-ZnO NPs can be applied as a biologically-derived nanotherapeutic agent.