Al Mustansiriyah Journal of Pharmaceutical Sciences

This study included synthesis of new serotonin derivatives in which imidazolidine rings are present in their structures. The final imidazolidine derivatives compounds were synthesized by reaction of synthesized



Schiff bases derivatives of serotonin with the glycine (NH2-CH2COOH) in presence of tetrahydrofuran (THF) as a solvent. The imidazolidine derivatives were identified by physical characteristics, FT-IR spectroscopy and 1H- NMR spectroscopy. Biological activities against two Gram negative (Klebsiella and E. coli) and two Gram positive (Streptococcus pyogenes and Staphylococcus aureus) bacteria were also distinguished. All the synthesized compounds III(a-d) exhibit moderate activities on four types of bacteria comparing with the activity of standard drug (Trimethoprim) but the highest activities of these compounds occur on Streptococcus pyogenes and their least activities occur on E. coli. The synthesized compounds were studied for the molecular docking to know the interaction and affinity of binding between them and bacteria

Metformin is 1,1-dimethylbiguanide hydrochloride, is the first-line therapy for type 2 diabetes. Additionally, several studies focused on the role of metformin in antioxidant activities for the treatment of hepatic disorders. The experimentally



-based result on valproic acid's liver injury, a front-line medicine for the treatment of epilepsy, attracted a lot of interest. As a result, the effect of metformin on valproic acid-induced redox disturbances in rat hepatic tissue was studied. metformin at 250 mg/kg dose was administered via oral gavage for 30 days, and valproic acid at a dose of 400 mg/kg was administered by intraperitoneal route starting from the twenty-second day of the experiment, for eight days to induce hepatotoxicity. Treatment with metformin reduced valproic acid-enhancing alanine aminotransferase, aspartate aminotransferase activities. Tissue levels of malondialdehyde in the liver tissue of valproic acid-treated rats significantly increased (P-value < 0.05) whereas glutathione decreased. The coadministration of metformin with valproic acid significantly decreased the malondialdehyde levels and increased glutathione levels (P-value < 0.05). Finally, metformin protected rats from valproic acid-induced hepatotoxicity, improved antioxidant status, and reduced hepatic oxidative stress.

A variety of new pyrazolines, isoxazolines, and amide derivatives were designed, synthesized, and tested in vitro for their cytotoxic potential against the breast cancer cell line MCF-7. Nabumetone is a prodrug that is used as non-steroidal anti-inflammatory drug



(NSAID). Before synthesis, the Molecular docking program (GOLD suite v. 5.7.1) was used to evaluate the selectivity for ER-α receptor, which demonstrated good agreement with the in vitro findings. Specifically, compounds 1e and 2e that target the ER- α receptor had the greatest PLP fitness values of (75.61 and 73.36), respectively, when compared to the tamoxifen reference medication, which had a PLP fitness of (92.78). The IC50 values for the synthesized compounds revealed that compound (1e) has a high IC50 value of 19 µM against MCF-7, compared to tamoxifen, which has an IC50 value of (18.02) µM.

Azithromycin is an antibiotic that belongs to the macrolide family used in a wide variety of bacterial diseases. However, it has been proposed as a potential therapy for the treatment of SARS-CoV-2 pneumonia (off-label use) given for its antiviral and



immunomodulatory activity. Never-theless, its role in the treatment of COVID-19 remains unclear. Azithromycin has a well-characterized safety profile. However, its use outside the approved indication needs further follow up to ensure that the benefit-risk balance remains positive. One method to look for new/ changed safety information is through using the information component (IC025) value. IC025 is the lower limit of a 95% credibility interval for the IC. The credibility interval provides information about the stability of a particular IC value: the narrower the interval, the higher the stability.

Objective:

Study the submitted adverse events reports of Azithromycin to the Iraqi Pharmacovigilance center and compare the occurrence of these reported adverse events in Iraq to the internationally reported cases during 2020COVID-19 pandemic using IC025.



Methodology:

The reported adverse events of Azithromycin to the national Pharmacovigilance database were studied qualitatively (age, gender and seriousness) and quantitatively (using IC025) as a measure of presence of a new/changed safety information related to Azithromycin.



Results:

The total number of reports for Azithromycin were 419, female represent (43%) and male represent (55.8%), and the predominant age groups was from 45-64 years representing (41.1%). The most widely reported adverse events were gastrointestinal disorders (68%), cardiac disorders (14.1%), general disorders and administration site effect (6.9%), and investigations (Interfere with Lab tests) (5.7%). There were 96 drug-adverse reaction combinations. The IC025 value for the most widely reported adverse events showed a comparable value for ECG-QT prolonged (3.6/3.7), Arrhythmia (0.6/0.7). There was a decreased value for palpitation (0.5/0.9) and dyspnea (0.3/0.6). Tachycardia and increased liver enzymes showed an increased value of (2.0/0.1) and (0.5/0.1) respectively.



Conclusion:

Using the IC025 was helpful in finding the increased reporting rate of adverse events compared to the background rate.

Methotrexate is used in the treatment of cancer, psoriasis, rheumatoid arthritis and several other disorders. It has a hepatotoxic potential side effect. Patients who have no access to alternative medications face a serious



challenge as a result. The current study aimed to assess the apoptotic potential of methotrexate on liver cells and evaluate the hepatoprotective activity of the potent antioxidant astaxanthin, by downregulation of apoptotic biomarkers caspase 9 and caspase 3.

A model of methotrexate-induced liver toxicity was employed on male rats. Thirty-six rats were divided into six groups; a negative control group, methotrexate induction group given (20 mg/kg) on day 13, three groups pretreated with astaxanthin in ascending doses (50, 75 and 100 mg/kg) for 14 days before methotrexate, and a conventional therapy group pretreated with silymarin (200mg/kg).

The use of methotrexate significantly increased liver tissue caspase 9 and caspase 3 compared to the negative control. On the other side, astaxanthin used in all three doses significantly normalized these biomarkers. This study revealed that since astaxanthin significantly decreased caspase 9 and caspase 3 that are involved in the apoptotic pathway, it could be used as pretreatment in patients treated with methotrexate to alleviate its hepatotoxicity.

An accurate prediction of the ligand-receptor binding free energies (ΔG) is a critical step in the early stages of rational drug design. The Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) method is a popular



approach to estimate ΔG. However, correlations between the predicted and the experimental ΔG are variable. The goal of this study is to investigate various approaches to optimize accuracy of the MM-GBSA method. A molecular dynamic (MD) simulations protocol was applied using penicillopepsin receptor against its inhibitor ligands, repeated 50 times for each complex system. After that, ΔG of the five inhibitors were predicted using MM-GBSA method. Moreover, a diverse ΔG values were calculated from the replicate MD simulations of each system. The results were showed correlations not only between the predicted and the experimental binding affinities of the systems but also between the predicted values and root-mean-square deviation. In addition, statistical analysis was evaluated the sample size.

This review is about 1,2,4-triazoles include their synthesis; their physio-chemical properties, SAR, reactions, derivatives. Finally, their biological activities with a demonstrated showing
different requirements to achieve different activity

Rosa canina belongs to rosacea family. Rosa. canina has a high concentration of phyto-constituents such as flavonoids, carotenoids, triterpene and vitamins as vitamin C, E, and A Rosa canina have an anti-inflammatory and antioxidant



effects. The antioxidant effect belongs to presence of large quantities of phytochemicals such as flavonoids and polyphenols. Rosa canina has been used for arthritis gout, osteoarthritis, urinary tract disorder, diabetes, inflammation and cancer. After grinding the leaves of Rosa canina, they are extracted by using ethanol solvent (cold extraction method), then the extract concentrated by rotary evaporator at 40 c° and leaving it to dry. Median lethal dose (LD50) has been examined on 84 mice (male and female) divided into seven groups, each one contains 12 (6 male and 6 female). The animals were monitored for signs and any behavior changes after administration of Rosa canina ethanol extract. Acute toxicity study was done on 20 rats (male and female for fourteen days. The weight of animals was taken at day 0, 7, and 14. At day fourteen, relative organ weight as well as histopathological examination for (heart, liver, spleen, kidney, lung, abdominal stomach, testes and ovaries) were taken. In addition to the serum biochemical tests for) blood glucose, urea, creatinine, ALT, AST and total bilirubin (were done at day fourteen. The result of this study, indicated that lethal dose 50 was 16.527 gram/kilogram. Acute toxicity study, revealed that there is no significant difference between relative organ weight of controlled and treated groups for all organs that were selected and mentioned above. In addition, there is no significant difference between serum biochemical tests for both controlled and treated groups. Finally, no changes have been found between controlled and treated groups regarding histopathology examination due to the p value was P ˃ 0.05.

Conclusion
According to the presented study, ethanol extract of Rosa canina showed wide range of safety depending on the result of lethal dose 50h (16.527 g/kg). Therefore, the extract considered nontoxic. No cytotoxic effect appeared by using ethanol extract of Rosa canina in acute toxicity study. This belongs to the results obtained, which include no significant difference between control and treated male and female rats in biochemistry tests and histopathological examination.