Al Mustansiriyah Journal of Pharmaceutical Sciences

In silico Study of New Five-Membered Heterocyclic Derivatives Bearing (1,3,4-oxadiazole and 1,3,4-thiadiazole) As Promising Cyclooxygenase Inhibitors

Safa Adnan Mahmood — 2024-07-09

A novel series of pyrazole, oxadiazole and thiadiazole bearing Nabumetone moiety were designed, synthesized, and evaluated for their anti-inflammatory activity against cyclooxygenase enzyme 2, after Insilico assay (by molecular docking study) a best set has been synthesized and characterized. After prediction of their activity by molecular docking study using Cambridge Crystallographic Data Base software tool (GOLD), We tested them in real in vivo as anti-inflammatory agents using egg white procedure. Due to their hydrogen bonding interaction with crucial amino acids in COX-2 isozymes Arg120, Tyr355, and Ser530, all tested compounds in molecular docking demonstrated significant activities compared with diclofenac, naproxen, and 6MNA as reference drugs. The data obtained from docking studies were highly correlated with that obtained from the in vivo assay in which compounds 3c, 6c, and 7c showed the best docking PLP fitness which were 91.35, 89.66, and 92.09 respectively with COX-2. Other compounds 2c, 4c, 5c, 6a, 6b, showed a PLP fitness above 80. The aim of this investigation was to produce novel NSAIDs, based on Nabumetone, that exhibit little or no gastro-toxicity and higher selectivity. This research offered helpful direction for the identification of novel pyrazole and thiadiazole anti-inflammatory compounds.

Drug Design, In Silico-Profiling of New Pyrrole Derivatives: Promising Anticancer Agents Against Acute Myeloid Leukemia

zaid alsalamy — 2024-07-09

Molecular docking simulation and synthesis of five compounds of N2, N4-bis (2-(4-substituted phenyl)-4-oxothiazolidin-3-yl)-3,5-dimethyl-1H-pyrrole-2,4-dicarboxamide was carried out to evaluate their theoretical binding affinities, targeting acute myeloid leukemia (AML). The chemical structure of the molecules was accurately drawn using ChemDraw Professional 19.1 software.

The designed compounds were evaluated for their selectivity towards FLT3's ATP pocket (PDB ID:6JQR) in comparison with the reference ligand (Gilteritinib) by using GOLD suite from the Cambridge Crystallographic Data Centre (CCDC) software (Version 2021.2.0). All the designed compounds exhibited good binding energies with the receptor active pocket and had promising activity. Compounds 2E and 3E showed the highest PLP Fitness (83.30, 80.86 respectively) and it is higher than that of Gilteritinib (71.91). In-silico ADME and drug-likeness studies were performed by using the Swiss ADME server. The results showed that most of the designed compounds expected to be absorbed from the GIT. Compounds 2B-E have high expected GI absorption. All the investigated compounds have no predicted BBB penetration. Additionally, compounds 2A, 2C, 2D, and 3A are not a substrate to P-gps which may indicate a lower expected incidence of resistance by cancer cells in vitro studies. Finally, all of the investigated compounds are not considered to inhibit CYP1A2 enzyme, except for compounds 2A and 3D.

Virulence Determinants of Acinetobacter baumannii Isolated from Different Infections in Baghdad Hospitals

Sajad Numan — 2024-07-09

Acinetobacter baumannii is an essential pathogenic bacteria cause nosocomial infections worldwide. The current work aimed to characterize several virulence factors in Acintobacter baumannii isolated from diverse clinical specimens in Baghdad.

Clinical samples including sputum, blood, urine, CSF and wound swabs were collected from patients who were admitted to hospitals in Baghdad. Identification of Acinetobacter baumannii isolates was performed using Vitek 2 system. Phospholipase (plcN) and elastase (lasB) genes were identified using Polymerase chain reaction (PCR) technique. Other virulence factors such as motility, biofilm formation,hemolysin production were screened.

Sixty-nine isolates were identified as Acinetobacter baumannii. The isolates were screened for Phospholipase (plcN) and elastase (lasB) production.The results of amplification revealed that out of the total isolates, 18 (26.6%) isolates included both (plcN) and (lasB) genes, 18(26.6%) isolates included only (plcN) and 23(33.3%) isolates have only (lasB).

Sixty (86.9%) isolates were positive for biofilm formation, 8 (11.6%) isolates indicated intermediate biofilm producers and 52(75.4%) isolates were weak biofilm producers. Sixty six A.baumannii isolates were motile on Nutrient agar (0.3%). Sixteen isolates were intermediate motile and 50 were highly motile. Positive association was found between the biofilm formation capacity and surface associated motility.

Fifty-seven isolates showed hemolysis on Blood agar on the second day of the incubation. Of these, 48 (69.56%) isolates show β –hemolysis and 9 (13.04%) isolates show α-hemolysis,

In Silico Prediction of Binding Affinities of Hybrid Molecules of Benzothiazole Linked with Hydroxamic Acid by Disulfide Bond and Certain Linkers with HDAC8 Enzyme

Mayssam Hazem — 2024-07-09

A new hybrid molecule of Benzothiazole cross-linked with hydroxamic acid through an amino acid or aminoalkanoic acid were synthesised. All the synthesized hybrid molecules (1-5) were subjected to molecular docking studies to evaluate their binding affinities with histone deacetylase enzyme (HDAC8, PDB ID: 1T69) and recorded lower ΔG (-8.276, -10.093, -8.647, -6.315, -8.676 kcal/mole, respectively) than the reference ligand (Vorinostat, suberoylanilide hydroxamic acid, SAHA -5.375 kcal/mole).

Molecular docking studies were performed using the maestro software (Schrödinger, version 2022-1). Moreover, compound 2, which is Benzothiazole-p-amino benzoic acid-hydroxamate has recorded the lowest binding score (-10.093). This may indicate that this compound is the most potent hybrid molecule. There were no violations from Lipinski’s rule and all the synthesized hybrid molecules comply with all parameters. Swiss ADME server was employed for the in silico molecular docking for prediction of the physicochemical and ADME properties of the investigated compounds. All hybrid molecules showed low possible passive oral absorption and no penetration into BBB. The hybrid molecules 1and 3 may be considered as P-gp substrates.

Prevalence of Cutaneous Adverse Drug Reactions According to Iraqi Pharmacovigilance Center; A retrospective study for 11 years (2010-2021)

Ahmed Sami — 2024-07-09

Background: Cutaneous Adverse Drug Reactions (CADRs) are among the leading causes of morbidity and mortality. Insufficient data exists on cutaneous adverse reactions, as many of these reactions are not reported due to their constantly changing patterns and the interaction of multiple risk factors.

Aim: This study aims to evaluate the prevalence of cutaneous reactions in Iraq and find the most commonly involved active ingredients with the commonest skin manifestations.

Method: A retrospective study based on the safety reports of patients having cutaneous reactions that were collected and submitted to VigiBase by the Iraqi Pharmacovigilance Center between 2010 and 2021. The study involved the analysis of gender, age, medicines, type of CADR, and seriousness of more than 4,300 reports.

Results: Skin rash was the most commonly reported CADR, and antibiotics were the leading drug class; ceftriaxone and vancomycin were responsible for 40.3% and 16.2% of the cases caused by antibiotics only, respectively. The mean age of the patients was 28 years, and the male-to-female ratio was 0.78:1. Out of the total number of cases, more than 1300 were deemed serious, and 15 patients have passed away.

Conclusion: Iraq comes in the 51^st place among other countries in the number of skin and skin-related ADR cases. Older adults are at higher risk of developing serious CADRs. Ceftriaxone and rash were the leading drug and cutaneous manifestations, respectively.

Hepatotoxic Effects of an Oral Amiodarone in White Albino Rats: Sub-Acute Biochemical, and Histopathological Assessments

Alzahraa Fatima Safa'a Fadhil — 2024-07-09

Amiodarone, potent antidysrhythmic, widely used drug that has been associated with hepatic toxicity in long-term or excessive use. In the presented study twelve rats were allocated into two groups and given daily doses via gastric gavage orally for two weeks as follows;

The first group served as a control normal group, whereas the second got amiodarone at a dosage of 300mg/kg/day orally. Liver tissues were processed for light microscopy, and blood samples were examined for serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and phospholipase a2 enzyme (Pla2) (which are thought to be an indicator of phospholipidosis and lipid buildup). Amiodarone was shown to produce hepatic histological abnormalities such as blood vessel congestion, leucocytic infiltration, liver degeneration, and stages of steatosis and necrosis of hepatocytes. The biochemical assessments were revealed that there was an elevation in amiodarone group's ALT and AST levels as a result of hepatic necrosis leading to leakage of enzymes content, while serum Pla2 was lowered significantly. Also, histopathology indicates stages of steatosis (Lipid accumulation) in hepatocytes, which may lead to farther damage in the late stages of hepatotoxicity.

Synthesis, Characterization, Docking Study and Biological Activates of New 3-Aminorhodanine Derivatives

Noor Alhuda Dakel khalaf — 2024-07-09

Abstract: Increase in fatalities among cancer patients is one of untreated facts and today cancer remains one of the main health issues. The most common cause of cancer death is lung cancer. Rhodanine has been recognized as a privileged scaffold in medicinal chemistry due to its well-known ability to demonstrate a broad range of biological activities,

and most of its derivatives exhibited remarkable anticancer activity in the (μg/mL) concentration range, while causing negligible cytotoxicity to normal cells. New N- and 5- disubstituted aminorhodanine derivatives were synthesized by Schiff base and Knoevenagel condensation reactions over two consecutive steps. Human cancer cells and Hdfn (human dermal fibroblasts isolated from neonatal foreskin) cells line, were used to evaluate the synthesized compounds’ activity by MTT assay. The new compounds revealed higher anticancer activity against A549 lung cells cancer when compared with reference drug Erlotinib (anticancer drug) and determined no toxicity or safety on normal cell. Among the tested compounds, 2b2 compound show potent anticancer activity which have IC₅₀ about (55.8 μg/mL).

Assessment of Factors Affecting Therapeutic Response of the DPP-4 Inhibitor Sitagliptin in A Sample of Iraqi Type 2 Diabetic Patients

Ahmad Nazar Jawad — 2024-07-09

Background: Type 2 diabetes is a complex and diverse disease, and the response to dipeptidyl peptidase-4 inhibitors may exhibit substantial variability between individuals. Several variables may play a role in variances in individual responses to treatment.

Objective: The purpose of the research was to assess the degree to which Iraqi patients with type 2 diabetes responded to sitagliptin and to investigate the factors that contribute to sitagliptin's overall efficacy.

Patients and methods: Eighty patients with type 2 diabetes who were using sitagliptin (100 mg per day) were included in this observational, cross-sectional study. Sociodemographic and patient clinical data were collected. Glycated hemoglobin (HbA1c), lipid profile parameters, and C-reactive protein were measured.

Results: The response rate to sitagliptin was 43.8%. Smokers and hypertensive patients, in addition to those not on diet, had higher HbA1c levels with nearly significant p values than non-smokers, normotensive patients, and those on diet, respectively. Poor response patients had higher levels of total cholesterol and triglycerides.

Conclusions: Possible variables that may have influenced the response to sitagliptin include smoking, hypertension, and an unhealthy diet. Furthermore, elevated levels of triglycerides may serve as an indicator of poor response.

Antihypertrophic Scar Effect of Iraqi Plantago major Extracts

Haider M. Badea Albadri — 2024-07-09

Background: Plantago major, historically renowned for its medicinal attributes across diverse cultures, has recently been under the research spotlight for its antihypertrophic scar effects.

Aim: To investigate the efficacy of Plantago major extracts in the treatment of hypertrophic scars, particularly comparing the effects of methanol and ethyl acetate extracts.

Methodology: Samples of the plant, procured from Baghdad's Al-Salihiya Neighbourhood in November 2021, underwent authentication at the Iraqi local Herbarium in the Al-Razi centre for alternative medicine. Using the Soxhlet apparatus, the dried plant material was extracted with methanol and subsequently partitioned with ethyl acetate. Both the ethyl acetate and methanol extracts were later formulated into ointments.

Results: The ointments were tested on hypertrophic scars induced in rats. Three groups of 12 rats each were used—ethyl acetate, methanol, and a control group using only Vaseline. Both extracts demonstrated efficacy in reducing scars, with the methanol extract showing more pronounced results.

Conclusion: The methanol extract displayed superior outcomes, potentially attributable to its richer phytochemical content compared to the ethyl acetate extract.

Evaluation of Nicorandil in Treatment of induced pulmonary arterial hypertension in male Rats

Taha Hashim Ahmed — 2024-07-09

Pulmonary arterial hypertension (PAH) is a chronic, rare, and non-treatable disease, resulting in elevated mean arterial pressure (≥25mmHg) during rest and (≥30mmHg) during exercise.

Pulmonary arteries remodeling including endothelial apoptosis, smooth muscle hyperplasia, and endothelial dysfunction are distinct features of PAH. This study aims to evaluate effect of nicorandil as an alternative treatment for PAH in comparison to tadalafil by evaluating its anti-inflammatory effect and histopathological changes. A total of 60 male wistar rats were divided to 6 groups, a control healthy group, and another 5 groups injected with monocrotaline to induce PAH. The induction group was left untreated while the other 4 groups were treated with either nicorandil or tadalafil, with or without treatment blockers (N-Nitroarginine methyl ester and glimepiride), after 21 days they were sacrificed for histopathology and measurement of inflammatory markers. Nicorandil reduced the levels of osteopontin, and cardiac marker brain natriuretic peptide (BNP) significantly (P≤0.05) , also it showed an improved histopathological picture of PAH by reducing smooth muscle proliferation, necrosis, and inflammation in pulmonary arteries. In conclusion, nicorandil in this study showed promising results in reducing inflammation and improving endothelial function.