Kufa Journal of Pharmaceutical Sciences

New azo - azo-containing and azo-metal complex derivatives of ciprofloxacin (D and E) were synthesized to increase its antibacterial activity and decrease the microbial resistance caused by different bacterial species. Many types of metal ions can be used, in our research we used Ag+2. Some of the physicochemical characteristics and FT-IR were used to confirm the chemical structure of the resulting compounds. In silico study was done by using a molecular operating environment program (MOE) and it was noticed that the synthesized compounds showed a high affinity to the target site in topoisomerase enzyme. These results were compatible with the in vitro biological study.

Prolonged QTc intervals are a common and clinically significant issue, associated with an increased risk of cardiovascular events and overall mortality. Medication-induced QT prolongation is a frequent cause, involving widely used drugs such as antiarrhythmics, antidepressants, antibiotics, and antipsychotics. Addressing this risk requires improved physician awareness and proactive monitoring. This cross sectional study aimed to enhance the practice of physicians toward drug-induced QT prolongation and related cardiac events. Conducted over three months from January 15 to April 15, 2025, the study took place at Imam Al-Sadiq Teaching Hospital in Al-Hilla. 53 physicians were interviewed regarding their knowledge, attitude, and practice toward QT prolongation. The majority of participating physicians were under 40 years old, predominantly male (67.9%), and most commonly specialized in internal medicine (45.3%). Regarding their years of practice, 37.7% had been practicing medicine for(less) than 5 years, (28.3%) had between 5 and 10 years of (experience, and 34.0% had over (10 years) of experience. In the term of knowledge, 5.7% of physicians have a good knowledge and 94.3% have a bad knowledge. Favourable attitude was present in 24.5%. Adequate practice was found in 67.9% while 32.1% of physicians had inadequate practice. This study shows a bad knowledge, unfavourable attitudes and adequate practices among physicians about drugs induced QT prolongation.

Hepatocellular carcinoma (HCC) is the most detrimental and intrusive state of liver cancer. The incidence of HCC resumed advancing rapidly, ranking as the sixth most common cancer and the fourth ultimate cause of death. To evaluate the utility of metformin and fluvastatin, alone or in combination, as potential anticancer therapeutics using human liver cell lines (HepG2). Four groups were allocated and treated for 24 hours as follows: The control)Group1) consists of HepG2 cells treated with 0.1% dimethyl sulfoxide with an average absorption at 570 nm of 0.651; the fluvastatin (Group 2)in (6.5, 12.5, 25, 50, and 100 μM) concentrations; the metformin (Group 3) in (6.5, 12.5, 25, 50, and 100 mM); and the (Group 4) of 10 mM metformin with fluvastatin in (10, 15, 20, and 40 μM) of HepG2 cell. The results revealed a synergistic effect between metformin and fluvastatin, where the combination is more effective in achieving an IC50 of about 25. These are more potent at reducing cell viability by about 44.62%. Also, combining of 10 μM metformin with 10 and 40 μM fluvastatin concentrations. A current study demonstrated that metformin and
fluvastatin separately reduced the viability of HepG2 liver cancer cells in a dose-dependent way. Also, when metformin (10 mM) was used together with fluvastatin (10–40 μM), it displayed stronger cancer-killing properties than using any drug by itself. These recommend a potential synergistic effect of the combination.

Proton pump inhibitors (PPIs) as one of the most frequently prescribed medications for their acid-suppressing effects. Their using continuously growing annually in all over the world. With the endless expansion of their market making the wide utilization of this pharmaceutical class frequently associated with notable instances of therapeutic inappropriateness where this phenomenon positions serious questions about the appropriateness of prescription of these drugs globally. Accordingly, current study aimed to evaluate the pattern of PPI using among patients within emergency department (ED) of single Iraqi hospital. Where there were no similar studies evaluate the appropriateness of PPIs use was had been made previously. An observational, prospective cross-sectional study performed in March 2024 included 188 patients who visited ED for non-surgical complaint at Al-Hakeem General Hospital in Al-Najaf city/Iraq. Of the total cohort, 43.09% of patients received a PPI as a part of their medical regimen in ED. Omeprazole was the mainstay prescribed medication among this medical class, it used in 91.35% of patients where it given as IV doses. Of the total patients who treated with PPI in ED, 23.45% were already taking a PPI as a part of their standard medical regimen before ED visit. Among patients received PPI in ED, 39.5% were on medication with an incorrect scheduling and/or dosage. The appropriateness, dosage and regimen correctness were noted to increase with age. Result of the current study revealed the over prescription of PPI both pre and throughout ED visit with an elevated % of inappropriate use in both settings.

Objectives: Due to its significant role in supporting the development and spread of cancer, the inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) of angiogenesis has been used in cancer treatment. The research presented created and synthesized a number of phenoxy benzoic acid derivatives. This work develops and evaluates four novel drugs targeting cancer and the VEGFR. For the chemical synthesis, we used phenoxy benzoic acid, sulphuric acid, methanol, hydrazine hydrate, Isatin derivatives, and glacial acetic acid. In vitro cell line investigations and in silico docking studies showed antitumor efficacy for the produced substances. The results demonstrated that the inclusion of isatin in the molecular framework enhanced receptor binding by interacting with critical amino acids essential for VEGFR-2 enzymatic activity. The docking study showed that compounds F1 and F4 had the highest binding affinities, with S-scores of -8.54 and -8.2, respectively, interacting with key amino acids such as Glu885, Cys1045, and Asp1046. The in vitro cytotoxicity results demonstrated selective anticancer activity. Compound F4 exhibited the highest potency against MCF-7 cells (IC50 = 5.76 µM), while F1 displayed notable activity against HepG2 cells (IC50 = 9.73 µM). Compared to sorafenib, the synthesized compounds showed selective cytotoxicity toward cancer cells while sparing normal cells. These findings suggest that the newly synthesized compounds could be potential VEGFR-2 inhibitors with selective anticancer properties. In conclusion, the synthesized Isatin-based 3-phenoxybenzoic acid derivatives exhibited strong VEGFR-2 inhibitory activity and selective cytotoxicity against cancer cells while reducing toxicity to normal cells.

Designing and evaluating six novel isatin-niflumic acid derivatives as a tyrosine kinase inhibitor of vascular
endothelial growth factor receptor-2 (VEGFR-2). Since there is overexpression of VEGFR-2 in aggressive
malignancies, including glioblastoma, hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and
non-small cell lung cancer (NSCLC), this overexpression leads to dysregulated angiogenesis and
uncontrolled cellular growth. Inhibiting VEGFR-2 kinase active site (PDB code: 4AG8) is a critical target
in developing anticancer medications, as it can aid in the prevention of tumor growth and metastasis through
blocking phosphorylation cascades required for endothelial cell proliferation and utilizing the molecular
operating environment to assess the binding affinity of novel design compounds against targeting proteins
(VEGFR-2) kinase active site. The docking outcomes depend on two important parameters, S-score and
RMSD, for investigating molecular interactions and drug discovery. The newly designed compounds (I-VI)
exhibit improved binding energy (S.score) ranging from -9.1782 to -9.5120 Kcal/mol and reduced RMSD
values ranging from 1.0608 to 1.8914 with the enzyme active site with additional four to five binding
interactions, in comparison to Sunitinib binding energy of -8.7276 Kcal/mol and RMSD value of 2.0611 and
only exhibit two binding interactions with the active site. These results suggest that the newly designed
compounds have the potential to be effective VEGFR-2 tyrosine kinase inhibitors when compared to the
reference ligand (Sunitinib).

Patients with COVID-19 are at risk for long-COVID (LC) symptoms after recovery. LC is associated with neuropsychiatric disorders and inflammatory symptoms. Depression is an important symptom that affects the everyday life of patients. In the present study, we recruited the leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), Gasdermin-D (GSDMD), and C-reactive protein as tools for prediction of depression in LC patients. Leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome overactivation brought on by severe acute respiratory syndrome in certain instances, cytokine storm is also caused by coronavirus 2 (SARS-CoV-2). Gasdermin-D (GSDMD) is cleaved by caspase-1 upon caspase-1 activation, which causes pyroptosis, an anticipated cell death. Patients with COVID-19 also have elevated levels of CRP, another biomarker. In patients with COVID-19, elevated CRP levels have been linked to higher mortality, inflammatory alterations in chest CT scans, and severe infection. A vital initial line of defense against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is innate immunity one However, dysregulated innate immune responses can be harmful, leading to an overabundance of proinflammatory cytokines that worsen tissue damage. As an intravascular effector of innate immunity, immunothrombosis refers to complicated networks of molecular pathways and cellular interactions functioning to restrict the survival and spread of pathogens. When pro-inflammatory cytokines like interleukin-6 (IL-6) are stimulated, the liver is the primary source of the acute-phase protein known as C-reactive protein (CRP). It is a proven biomarker for tracking COVID-19 patients' rates of inflammation. By attaching itself to pathogen surfaces and injured cells, CRP plays a crucial part in triggering the innate immune response. Serum levels of NLRP3, GSDMD, were measured using the ELISA technique. Depression symptoms were estimated using the Hamilton depression (HAMD). Results indicate a substantial rise (p<0.001) in median CRP levels in LC+Dep and LC groups compared to the control group. Serum NLRP3 levels were considerably higher (p<0.001) in the LC+Dep group compared to LC patients and the control group. The LC+Dep and LC groups had considerably greater GSDMD levels (p<0.001) than the control group, which had the lowest value. The partial correlation study among the study groups after controlling for age, weight, height, BMI, and smoking in LC patients showed significant correlation between total HAMD score and CRP, GSDRMD, and NLRP3. GSDMD has the best diagnostic ability for depression in LC patients at a cut-off value of 60.98 pg/ml indicating that the subjects may predict depression in LC patients with a significant sensitivity (69.8%) and specificity (69.9%). The present study revealed the importance of inflammation and NLRPs and GSDMD in the pathophysiology of the LC symptoms. DSDRMD is the best predictor for depression in LC patients.

Patients with chronic kidney disease (CKD), irrespective of the extent of renal impairment, are acknowledged to have an elevated risk for venous thromboembolism (VTE) and stroke; yet, study findings on the association between CKD and the heightened risk of VTE and stroke have been inconclusive. Venous thromboembolism (VTE) predominantly arises during hospitalization for significant surgical procedures or trauma, however it may potentially manifest several months post-surgery. The quantity of anticoagulants approved for the prevention and treatment of thromboembolic disorders has risen. Irrespective of the anticoagulants employed, prior studies indicated that improper utilization in patients with renal impairment elevates the risk of hemorrhage. An interventional study was done to evaluate the proper utilization of anticoagulants in patients with renal impairment within healthcare institutions in Najaf Province. Intervention consists of lectures, brochures, rollups and buck lists about updated guideline of safe anticoagulant use in patients with renal impairment. The study included two patients\' groups according to receiving intervention or not. the appropriateness of intervention was assessed at 3 periods preintervention, 4 weeks after-intervention and 12 weeks after intervention according to CHAD-VASC scoring system for stroke risk and PADUA scoring system for VTE risk. Results shown that at baseline there were no significance difference between two groups according to Chi-square analysis with respect to inappropriate prescribing of anticoagulants. After 4 weeks of intervention the significant decline in percentage of patients receiving inappropriate anticoagulants (9%) in comparison to patients not received intervention (23.5%). After 12 weeks of intervention the is significant decline in percentage of patients receiving inappropriate anticoagulants (2.5%) in comparison to patients not received intervention (21.5%). The results also shown that inappropriate prescribing has been improved dramatically after 12 weeks in comparison to 4 weeks of intervention. This study demonstrated that appropriate prescribing of anticoagulants in CKD patients significantly improved following the intervention and prolonged monitoring is advised to evaluate the enduring effects of this intervention.