Iranian Journal of Pharmaceutical Sciences
Volume:19 Issue: 1, Winter 2023

A new series of derivatives of N, 2-diphenylquinazolin-4-amine (3a-g) was synthesized through nucleophilic substitution. The structures of compounds were characterized by FTIR, 1H-NMR, and 13C-NMR spectroscopy. All synthesized compounds were evaluated for their antimicrobial activities against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Lactobacillus rhamnosus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and also for antifungal activities, against Candida albicans, using broth microdilution method to determine their minimum inhibitory concentrations (MIC). Most of the compounds have shown moderate to good antibacterial activities, significantly compound 3g at 0.0625 mg/mL concentration had the highest activity against P. aeruginosa. Also, the MIC of compound 3f was 0.0078 mg/mL against S. aureus. Furthermore, the tested compounds exhibited remarkable antifungal activities against C. albicans, significantly compounds 3c and 3g showed the least MIC (equal to 0.0625 mg/mL). Also, a docking study into DNA gyrase has been made for these compounds. The synthesized compounds showed dock score values between -3.05 and -6.13kcal/mol. The highest dock score among them was -6.13 kcal/mol, found for compound 3c.

Lorcaserin is an anti-obesity agent used to treat chronic obesity. It is a selective 5-HT receptor agonist. Lorcaserin tablet formulation is not marketed in India but was available in the US and the patent expiration happens to be in 2023, there is greater scope for the launch of generic drugs in India as well as other countries. The literature review reveals that there are several clinical data for the estimation of Lorcaserin was reported so far but there are few Analytical reports available. Therefore, the attempt at method development and validation of Lorcaserin raw material was undertaken by various analytical methodologies such as Titrimetry, UV, and HPLC methods. But Lorcaserin tablet (Belviq) was withdrawn from US Market on Feb 13, 2020, due to cancer risk. In this view, the synthetic mixtures were prepared and evaluated by the proposed HPLC Method. The developed titrimetry, UV, and HPLC methods are easy to perform and specific to Lorcaserin and pay a wider way to the characterization of newer drug substances and formulations.

The aerial parts essential oils of nine populations of four Nepeta species (N. straussi Hausskn. & Bornm., N. amoena Stapf., N. haussknechtii Bornm. and N. speciosa Boiss. & Noë), from Iran, were analyzed by gas chromatography, flame ionization detector (GC-FID), and mass spectrometric detection (GC/MS). In the oil of one population of N. straussi, 1,8-cineole (40.1%) was the main constituent. In contrast, the oil of the second population consisted of germacrene D (11.6%), caryophyllene oxide (11.9%), and n-nonadecane (10.3%) as major compounds. Caryophyllene oxide (36.2%) in one population and hexadecanoic acid (33.4%) in another population of N. amoena were the major compounds. In the oils of two populations of N. haussknechtii, 1,8-cineole (45.1% and 48.6%) was the main constituent, while 4aα-7α-7aα-nepetalacton (26.7%) and 1,8-cineole (24.5%) were major components in the oil of third population. In the essential oil of one population of N. speciosa, 4aα-7β-7aα-nepetalacton (74.8%) and the other population, 1,8-cineole (32.3%), were the main constituents. Therefore, in addition to variations between essential oil compositions of different Nepeta species, there are variations in the oil composition of one Nepeta species from different localities that may be due to climatic conditions or having the potential to form chemotypes.

Interest in essential oils is continuously increasing due to their biological activities in various fields, from pharmaceuticals to food and agriculture. Essential oil is unstable and hydrophobic under normal storage conditions. Thus, it can quickly lose its anti-fungal and antibacterial activity. The new method of nano-emulsion production has been proposed as an effective solution to increase their stability and activity. In this study, the nano-emulsions of Myrthus communis, Rosmarinus officinalis, and Eryngium campestre essential oils were formulated using different proportions and evaluated on Candida albicans. Nano-emulsions were prepared using an ultrasonic method, and the field emission scanning electron microscopy (FESEM) apparatus determined the size of the prepared nano-emulsion particles. The dilution method determined the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC). Also, the bioassay of plant compounds was investigated using the agar well diffusion method. Mean droplet size of M. communis, R. officinalis, and E. campestre nanoparticles were reported in 200-500, 100-200, and 200-300 nm, respectively. The lowest MIC value was obtained for the M. communis (12.5) and R. officinalis (12.5) nano-emulsion. The activity of the essential oil and nano-emulsion of the tested plants against C. albicans was confirmed with an inhibition zone diameter of 3.9-27.5 mm. Examining the time growth curve of C. albicans showed that nano-emulsions were significantly more effective on the fungal pathogen than essential oils. Results show that using nano-emulsions increases the antimicrobial properties of essential oils from medicinal plants.

Primary Sjogren syndrome (PSS) is one of the most common systemic autoimmune diseases. Lymphocytic infiltration of exocrine glands, especially lacrimal and salivary in PSS, causes ocular and oral dryness. Dry mouth may lead to difficulty in speaking, chewing, and swallowing and result in reduced quality. The pathogenesis of PSS involves multiple factors, such as genetic, environmental, and immunological factors. Despite extensive research over the last few decades, the exact etiology and progression of PSS and its inflammatory lesions is still unknown. Gene co-expression network analysis (WGCNA) is a system biology method that can be used to describe the correlation between different genes and find modules of highly correlated genes and key genes. Also, by using these modules, we can get gene ontology information and biological pathways. In this study, we used WGCNA to analyze the GSE40611 dataset, which consists of 17 PSS patients and 18 healthy controls. We construct a co-expression network for mRNA expression data of patients and control groups and then find the most significant module and hub genes that play important roles in PSS. We also identify biological pathways and related miRNA for hub genes. Among all the modules, turquoise had the most correlation with PSS and some of the hub genes, including GPR18, FCRL1, VNN2 and etc. Also, a large number of pathways were identified in the turquoise module, most of them related to immune system activity, like T-cell activation, lymphocyte differentiation, leukocyte and lymphocyte activation, regulation of immune system processes, regulation of immune response, and cell-cell adhesion. External validation using bulk RNA sequencing data also confirmed the presence of selected hub-genes in pathogenicity of PSS. Finally, these results can lead to finding key players in treatment of PSS.

Mometasone furoate is a synthetic glucocorticoid with anti-inflammatory and anti-allergic effects, used for the treatment of allergic rhinitis, asthma, and dermatoses. In this study, a spectrophotometric method, as a selective and sensitive method, was developed for the determination of mometasone furoate after derivatization. For this purpose, mometasone was first reacted with sodium cyanide to prepare the drug derivatives. After that, the effects of different variables such as reaction solvent, concentration of the reagents, pH, and reaction time were studied. The final results showed that the determination method was linear in the range of 2-18 μg/ml. It seems that after 24 hours, the reaction was complete. The reaction product was characterized by NMR and FT-IR spectroscopy, and the accuracy and precision of the developed method were also studied. At last, the method was checked on Mometasone Ointment (0.1%), and the results were compared with the results of the HPLC method as a standard method.

Milicia excelsa stem bark is applied in traditional medicine in some African societies, primarily as a tonic to rejuvenate the body after demanding episodes. However, there is a paucity of scientific evidence to support this usage. Therefore, this research aimed to evaluate the anxiolytic and anti-stress potentials of ethanol extract of the stem bark of Milicia excelsa (ESBME) in mice. The central nervous system inhibitory effect of the extract was determined using novelty-induced rearing, grooming, and locomotion behaviors while the anxiolytic effect was investigated by using a hole board and elevated plus maze (EPM) test models. The extract’s ability to alleviate the anxiety-like and depressive-like behaviors triggered by acute restraint stress was evaluated with the use of EPM and tail suspension test respectively. The ESBME significantly (p<0.05) decreased the novelty-induced rearing, grooming, and locomotion behaviors indicating a central nervous system inhibitory effect. At 37.5 mg/kg, ESBME significantly (p<0.05) increased the number of head poking in the hole board test designating anxiolytic potential. Subsequently, the ESBME significantly (p<0.05) increased the percentage of open-arm entries and percentage open-arm duration as well as reducing the anxiety index on elevated plus Maze consistent with the antianxiety effect. The extract also significantly (p<0.05) alleviated the anxiety-like and depressive-like behaviors triggered by acute restraint stress suggesting an anti-stress effect. In conclusion, ESBME possesses central nervous system inhibitory, anxiolytic, and anti-stress effects thereby providing scientific evidence to the ethnomedicinal claim of the plant as an anti-stress agent.

The aim of this study was to investigate the effects of long-term administration of clenbuterol on the histomorphometry and histopathology of testicular tissue in mice. 30 male NMRI mice were divided into three groups including the control group that received (0.1 ml of normal saline) the second group, (2.5 mg /kg clenbuterol) and the third group (8 mg/kg clenbuterol) that received for 30 consecutive days. At the days 3 and 30 from the beginning of the study, five mice were randomly sacrificed from each experimental group. The testicular tissue was removed from the right testis and fixed in the Bouin's solution for histomorphometric and pathological examinations. Degenerative lesions including distortion of the germ cells, reducing their number, and presence of vacuoles within the seminiferous epithelium were demonstrated in the clenbuterol treated groups. At the present study, administration of clenbuterol decreased spermatogenesis parameters including meiosis index, Johansen score, spermatogenesis percentage, seminiferous tubules diameter and epithelium height of seminiferous tubules both in the day 3 in low and high dose of clenbuterol with more severity in high dose. On the 30th day, testicular degenerative changes due to clenbuterol were more in the low dose of rather than high dose. According to the obtained results, it can be concluded that administration of clenbuterol may has potentially negative affect on the sperm production and fertility in male mice.