Al Mustansiriyah Journal of Pharmaceutical Sciences

Acute kidney injury (AKI) is characterized by a sudden loss of kidney function that is established by increased serum creatinine levels and decreased urinary output. AKI is one of a group of functional kidney conditions

known as acute kidney disease and disorders (AKD), which can vary in severity and self-limiting to severe and chronic. Adminstrations of glycerol generate significant elevation in serum urea and creatinine that’s mean occurance of functional abnormalities in the kidney. Vinpocetine drug has many pharmacological targets with multiple action, phosphodiesterase inhibiters-1(PDE-1) inhibitor, a voltage-gated sodium channel, and Inhibitory kinase B (IKK) are 3 main molecule targets of vinpocetine. PDE1 has been implicated in the regulation of vasoconstriction, vascular and cardiac structure remodeling, and neuro-transmission. Cilostazol, a phosphodiesterase (PDE) III inhibitors, that widely used for many cases such as reduces direct vascular injury via different mechanism, such as vasodilation and antiplatelet action, anti-inflammation and platelet-leukocyte interaction minimisation, and inhibition of vascular proliferation via up-regulation of hepatocyte growth factors. In present study, we looked at the effect and mechanism of the drugs vinpocetine and cilostazol in an animal model of glycerol-induced AKI. Experiment done during the 14-day trial, rats were divided into five groups: the control group received 2ml/kg normal saline; the induction group received 10ml/kg intramuscular glycerol injection; the vinpocetine group received 5mg/kg via gavage for 14 days and on day 7 given glycerol IM, the cilostazol group received 50mg/kg for 14 days and on day 7 given glycerol IM, and the combination group received half dose vinpocetine (2.5mg/kg) and cilostazol (25mg/kg). We discovered that the induction group had higher levels of urea and creatinine, as well as increased inflammation and oxidative stress, and that their renal tissue showed morphological changes typical of AKI, whereas the combination groups reduced glycerol induce acute renal damage. This revealed that vinpocetine and cilostazol can reinforce renal rat protection by reducing serum urea and creatinine and improving histopathological changes.

Dihydrofolate reductase (DHFR) is a fundamental enzyme in producing the precursor of purines and pyrimidines for biosynthesis of DNA, RNA and amino acids at various stages. It is considered the key target for both anticancer and antimicrobial drug design.

Terminalia chebula has unique phytoconstituents which are employed broadly in the development of medications against different diseases. It has been established that Terminalia chebula fruit could be used as therapeutic agent for cancer treatment. The aim of study was to evaluate the inhibitory effect of T. chebula fruit extract against DHFR enzyme activity and assessment the antioxidant and scavenging activity of T. chebula fruit extract, using DPPH and reducing activity tests Terminalia chebula fruits where extracted. The anti- DHFR enzyme activity was assessed in vitro for the four extracts of Terminalia chebula fruit and MTX. Phytochemical analysis of screening test, gas chromatography-mass spectrometry (GC-MS) analysis and high-performance liquid chromatography (HPLC) was done for the extract with highest biological activity. Antioxidant and radical scavenging activity of the extract with highest biological activity were evaluated via DPPH [1, 1-diphenyl-2-picrylhydrazyl (α, α-diphenyl-β-picrylhydrazyl] and reductive ability test. The percent of DHFR inhibiting activity for the cold methanolic extract was the highest and it was higher than that of MTX (96.0±1.4% vs. 89.0±1.1%, respectively), therefore, it was selected for the proceeding assay. Phytochemical analysis showed that the cold methanolic extract of T. chebula, showed a positive reaction for alkaloids, flavonoids, phenolic compounds, steroids and saponins. Besides, GC-MS analysis showed the presence of pyrogallol compound, while HPLC analysis recorded 3 major peaks with different retention times that were semi-identical to gallic acid, rutin and quercetin standard. The highest radical scavenging activity of T.chebula cold methanolic extract and ascorbic acid according to DPPH were (80.1±2.04% and 85.83±2.1%, respectively) at the maximum studied concentration (200μg/ml), where the activity of ascorbic acid was significantly higher (p≤0.05) than that of T.chebula. Meanwhile, the reductive ability of the cold extract was significantly higher (p ≤ 0.05) than that of vitamin E (0.72±0.15 and 0.41±0.08, respectively) at the maximum studied concentration (250μg/ml). These results suggesting the cold extract of Terminalia chebula has in vitro prominent anti-dihydrofolate reductase activity which is better than that of MTX.

Study of the pharmacological activity of new heterocyclic scaffolds becomes a passion of many medicinal chemists around the world. 1,2,4-thiadiazine 1,1-dioxide derivatives are one of the heterocyclic derivatives that haveattracted researchers' attention since the early 1940's. In spite of this, however, the study of the pharmacological activities of this nucleus remains scant and needs to shed lighter on it. Therefore, in this review, the authors in this review collected all the families that included this nucleus whose biological activities were studied for the period between 1993 and 2020 in order to get an idea of the effectiveness of these compounds and highlighted the most effective ones. In addition, knowing the pharmacological aspects that had not been studied previously to focus more on them in the future by interested researchers.

Mucopolysaccharidosis I (MPS I) or Hurler and Mucopolysaccharidosis VI (MPS VI) or Maroteaux-Lamy syndrome are infrequent genetic disorder inherited as an autosomal recessive disease attributed to genetic



variants genetic variant causing α-L iduronidase (IDUA) and arylsulfatase B (ARSB)enzyme deficiency, respectively. Here, two cases of children suffering from MPS disorder were described, the first case was MPS I while the second case was MPS VI and both cases were treated with allogenic Hematopoietic Stem Cell Transplantation approach in order to limit skeletal deterioration and retard neurocognitive alterations and hence, improve the quality of life of affected children. Following Transplantations outcomes reveal a full engraftment of donor cells as well as improvement of recipient enzymatic activity, enzyme replacement therapy post-transplantation will augment transplantation clinical outcomes. Transplantation will be more successful if the disease diagnosed early before the severe irreversible symptoms ensue.

Oxazine and thiazine are heterocyclic organic compounds that have a wide range of pharmacological applications. In this study, some chalcone derivatives (1–5) were synthesized based on the reaction of an equal amount of p-substituted acetophenone and terephthalaldehyde in a basic medium. Oxazine derivatives (6-10) and thiazine derivatives (11–15) are synthesized from the reactions of chalcones (1-5) with urea and thiourea, respectively, in a basic medium. The newly synthesized compounds were identified using various physical techniques like 1H-NMR and FT-IR spectra, in addition to docking analysis for some of these derivatives. Finally, these compounds were tested for their biological activity, IC50, and % of PC3 cell line viability as markers of anticancer activity.

A series of nine novel 4, 5-dihydro-1H- pyrazole-1-yl acetate derivatives (IVa-i) by Shahlaa et al. was investigated in vitro for their antiproliferative activity against two cancer cell lines, breast cancer cell line (MCF-7) and lung cancer cell lines (A549), According to



the cytotoxicity effect of these compounds, IVa, IVc and IVi compounds have antiproliferative effect with percentage (81.30%, 87.4% & 54.66%) respectively at 72h treatment on MCF-7 cell line compared to other compounds, these results indicate that the new compound IVc have the higher antiproliferative percent comparable to tamoxifen as a standard anti-tumour for oestrogen receptor positive breast cancer cell line after 72h followed by IVa after 72h (83.31%). cytotoxicity effect of compound IVb was highest among tested compounds on lung cancer cell line (A549) with antiproliferative percentage (58.49% & 75.04%) at 48 & 72h respectively, but it is less than erlotinib as a standard anti-tumour for lung cancer cell line cytotoxicity effect (77.10% & 82.46%) at these times. three compounds (IVa, IVc & IVi) have antiproliferative effect on breast cancerous cell line (MCF-7) and compound (IVc) have inhibition percentage comparable to that of the authorized medication Tamoxifen. One compound (IVb) had antiproliferative activity, but less than that of erlotinib on lung cancerous cell line (A549) and there is good agreement between our docking results and the experimental results.

Anastrozole (ANZ) is a potent non-steroidal aromatase II inhibitor (AI) used to decrease or delay the progression of breast tumor growth in some women. Since ANZ could be delivered transdermally due to its physicochemical characteristics as (log p of 3.5, aqueous solubility of 0.5 mg /mL, low dosage and half-life of 46.8 hr.) so, it could be used as a modelling drug evaluation of ethosomes, the current study aimed to formulate ANZ loaded ethosomes and evaluate the formulated ethosomes for particle size and PDI, entrapment efficiency and in vitro release profile. Film hydration method was used to prepare ANZ-loaded ethosoms. using different ratios of phospholipid (Soy phosphatidyl choline) and ethanol at variables probe sonication energy and time ratios.

polydispersity index and particle size were used to evaluate the prepared ANZ-loaded ethosoms. The optimized formula of ethosomes which contain (1% Soy phosphatidyl choline,20% ethanol subjected to 300watt sonication energy with 1/3 sonication on /off ratio) was studied for in vitro drug release. It had 127.75±0.36 nm particle diameter and 74.7136 ± 3.457 % entrapment efficiency, the release kinetics obey Korsmeyer-Peppas and non-Fickian release as R2=0.9779 and n=0.737.

The ratios of Soy phosphatidyl choline, ethanol, sonication energy and duration had a significant impact on the particle size of ethosomes at (p0.05). The preformulating analysis of Powder X-ray diffraction (P-XRD) indicate amorphous ethosomes. Fourier transform infrared (FTIR) showed the inertness among components.