Inas Almazari
@zu.edu.jo
Clinical pharmacy/College of pharmacy
Zarqa University
RESEARCH INTERESTS
Biochemistry, cancer, chemoprevention, anti-oxidants, Nrf2, NfkappaB, anti-inflammatory
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Mohammad Abu Assab, Hamza Alhamad, Inas Almazari, Bilyana Azzam and Hanadi Abu Assab
The medication review process (MRP) is an extended, vital role of community pharmacists in improving health outcomes of medication use, yet it is neither systematically nor comprehensively provided bycommunity pharmacies in Jordan. This study aimed to identify the potential barriers hinderingMRP implementation bycommunity pharmacists in Jordan. A total of 550 community pharmacists electronically received a previously constructed and validated Arabic questionnaire explicitly developed to assess the current medication review practices and factors hindering the MRP, of whom 417 answered the questionnaire, giving a response rate of 75.8%. Among the investigated six categories’ seventeen barriers tothe implementation of the MRP, the highest rating was found for remuneration barriers (55.8%), followed by barriers related to regulations and patients, which scored 52.3% and 48.8%, respectively. Resource-related barriers were recognizedby 44.6% of participants, while qualifications and barriers related to physicians scored 42.9% and 41.8%, respectively. Although community pharmacists in Jordan are eager to extend their roles from traditional to more patient-centered ones, they encounter various barriers hinderingsuch development. Regulation adjustments accompanied by cost-effective remuneration and proper training are strong facilitators for community pharmacists to initiate the medication review service; make available the needed resources; and invest efforts, time, and money to operate it.
Mahmoud A. Al-Sha'er, Inas S. Almazari, and Mutasem O. Taha
Wiley
Inhibitor kappa‐B kinase‐beta (IKK‐β) controls the activation of nuclear transcription factor kappa‐B and has been linked to inflammation and cancer. Therefore, inhibitors of this kinase should have potent anti‐inflammatory and anticancer properties. Accordingly, we explored the pharmacophoric space of 218 IKK‐β inhibitors to identify high‐quality binding models. Subsequently, genetic algorithm‐based quantitative structure activity relationship (QSAR) analysis was employed to select the best possible combination of pharmacophoric models and physicochemical descriptors that explain bioactivity variation among training compounds. Three successful pharmacophores emerged in 2 optimal QSAR equations (r12175 = 0.733, r12LOO = 0.52, F1 = 65.62, r12PRESS against 43 test inhibitors = 0.63 and r22175 = 0.683, r22LOO = 0.52, F2 = 72.66, r22PRESS against 43 test inhibitors = 0.65). Two pharmacophores were merged in a single binding model. Receiver operating characteristic curve validation proved the excellent qualities of this model. The merged pharmacophore and the associated QSAR equations were applied to screen the National Cancer Institute list of compounds. Ten hits were found to exhibit potent anti‐IKK‐β bioactivity, out of which, one illustrates IC50 of 11.0nM.
Mahmoud A. Al-Sha’er, Iman Mansi, Inas Almazari, and Nancy Hakooz
Elsevier BV
The pharmacophoric features of the virtual co-crystallized protein of 17 Akt1 proteins were downloaded from the protein data bank, and explored to end up with 132 generated pharmacophores that had been evaluated using the decoy list composed of 1724 compounds. The areas under the curve of the Receiver-Operating Characteristic (ROC-AUC) were sorted, and the highest ranked pharmacophore 3MV5_2_01 was selected to be used as a searching tool in the National Cancer Institute (NCI) database. The captured hits were mapped based on successful hypotheses and the best fitted compounds were selected. The inhibition of Akt1 was measured and expressed as a percentage of inhibition. 24 out of the 40 compounds showed inhibition of Akt1, out of which 13 compounds showed more than 50% inhibition. Compound 1 showed 93.3% inhibition at 100 μM concentration. To confirm the inhibition of Akt1 phosphorylation, MCF10A cell line was co-treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) and 100 μM of each of the most potent 13 Akt inhibitors (1-13). It was found that compounds 1 exert 91.6% inhibition of Akt1 phosphorylation in MCF10A cell line.
I. Almazari, J.-M. Park, S.-A. Park, J.-Y. Suh, H.-K. Na, Y.-N. Cha, and Y.-J. Surh
Oxford University Press (OUP)
Guggulsterone (GS) [4,17(20)-pregnadiene-3,16-dione] is a phytosterol found in the gum resin of the Commiphora mukul. GS exists naturally in two stereoisomers: E-GS (cis-GS) and Z-GS (trans-GS). In this study, the effects of both isomers on expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) were evaluated in human mammary epithelial (MCF10A) cells. NF-E2-related factor 2 (Nrf2) is considered a master regulator in activating antioxidant response element (ARE)-driven expression of HO-1 and many other antioxidant/cytoprotective proteins. cis-GS upregulated the transcription and protein expression of HO-1 to a greater extent than did trans-GS. cis-GS treatment enhanced nuclear translocation and ARE-binding activity of Nrf2. MCF10A cells transfected with an ARE luciferase construct exhibited significantly elevated Nrf2 transcriptional activity upon cis-GS treatment compared with cells transfected with the control vector. In addition, silencing of the Nrf2 gene abrogated cis-GS-induced expression of HO-1. Incubation of MCF10A cells with cis-GS increased phosphorylation of Akt. The pharmacological inhibition of phosphoinositide 3-kinase (PI3K), an upstream kinase responsible for Akt phosphorylation, abrogated cis-GS-induced Nrf2 nuclear translocation. Pretreatment with the thiol-reducing agents attenuated Akt phosphorylation, Nrf2 activation and HO-1 expression, suggesting that cis-GS may cause thiol modification of an upstream signaling modulator. Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN) is a negative regulator of the PI3K-Akt axis. The mutation in cysteine 124 present in the catalytic domain of PTEN abolished cis-GS-induced HO-1 expression as well as Akt phosphorylation. Whether this cysteine is a 'bona fide' target of cis-GS in its activation of Nrf2 needs additional investigation.
Hyun-Hee Lee, Sin-Aye Park, Inas Almazari, Eun-Hee Kim, Hye-Kyung Na, and Young-Joon Surh
Elsevier BV
Piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene), derived from the seeds of Euphorbia lagascae, has been reported to have anti-proliferative, anti-inflammatory, and antioxidant properties. However, the mechanisms underlying its chemoprotective effects remain largely unresolved. In the present study, we found that piceatannol treatment (30 microM) significantly upregulated the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) and its mRNA transcript at 6h and 3h, respectively in human breast epithelial (MCF10A) cells. A redox-sensitive transcription factor NF-E2-related factor (Nrf2) plays a pivotal role in induced expression of many cytoprotective enzymes including HO-1. Piceatannol induced translocation of Nrf2 into the nucleus and its transcriptional activities when treated to the MCF10A cells for 6h. Upregulation of HO-1 expression by piceatannol through direct binding of Nrf2 to antioxidant response element (ARE) was verified by the chromatin immunoprecipitation (ChIP) assay. siRNA knock down of Nrf2 gene abolished piceatannol-induced HO-1 expression. In addition, piceatannol-induced activation of Nrf2 and/or HO-1 expression was abrogated by the pharmacological inhibitor (LY294002) as well as the kinase-dead form of Akt. In an attempt to elucidate the molecular mechanisms underlying cytoprotective or chemoprotective activity exerted by piceatannol, we examined its effect on the signaling pathways responsible for induction of HO-1 expression. We hypothesize that an electrophilic quinone formed as a consequence of oxidation of piceatannol bearing the catechol moiety may bind directly to Kelch-like ECH-associated protein 1 (Keap1), an inhibitory protein that sequesters Nrf2 in the cytoplasm. This will diminish the affinity of Keap1 for Nrf2. The thiol reducing agents, dithiothreitol (100 microM) or beta-mercaptoethanol (1.4 microM), attenuated piceatannol-induced Nrf2 activation and HO-1 expression. It is hence likely that piceatannol modifies specific cysteine residues of Keap1, which allows Nrf2 to translocate into the nucleus and bind to ARE, leading to enhancement of the expression of HO-1. The characteristic catechol moiety of piceatannol appears to be critical for induction of Nrf2 activation and subsequent upregulation of HO-1.