Publications by authors named "Sami I Alzarea"

8 Publications

  • Page 1 of 1

6-Shogaol attenuated ethylene glycol and aluminium chloride induced urolithiasis and renal injuries in rodents.

Saudi J Biol Sci 2021 Jun 14;28(6):3418-3423. Epub 2021 Mar 14.

Department of Pharmaceutics, College of Pharmacy, Jouf University, Aljouf 72341, Saudi Arabia.

The 6-shogaol, is a flavanone type flavonoid that is abundant in citrus fruit and has a wide range of pharmacological effects. The present study attempted to evaluate the antiurolithic effect of 6-shogaol on ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. The efficacy of 6-shogaol 50 mg/kg and 100 mg/kg was studied in EG 0.75% (V/V) and AC 1% (W/V) experimentally induced urolithiasis in rats for 21 days. The weight difference, urine volume, the levels of calcium, phosphate, magnesium, oxalate and uric acid in urine was observed. The blood urea nitrogen, creatinine, uric acid in serum and levels of malondialdehyde (MDA) and glutathione (GSH) were also measured. Histopathological analyses in kidneys were also performed. The rats weights were higher in the 6-shogaol groups than the urolithiasis group. EG caused a significant increase in serum creatinine (p < 0.05), BUN (P < 0.001), and uric acid (p < 0.01) while treatment with Cystone (750 mg/kg), and 6-shogaol (50 and 100 mg/kg) showed the significant reduction in increased serum levels of creatinine (p < 0.001), uric acid (p < 0.01) and BUN (p < 0.001). Administration of EG and AC showed statistically significant (p < 0.001) elevated levels of MDA and reduction in GSH levels. Treatment of Cystone (750 mg/kg), and 6-shogaol (50 and 100 mg/kg) significantly (p < 0.001) reduced MDA levels and an increase GSH levels as compared to EG and AC-treated group. The histological findings further attested antiurolithiatic properties of 6-shogaol. The present study attributed clinical shreds of evidence first time that claiming the significant antiurolithic effect of 6-shogaol and could be a cost-effective candidate for the prevention and treatment of urolithiasis.
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http://dx.doi.org/10.1016/j.sjbs.2021.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176042PMC
June 2021

Cytotoxic Potential, Metabolic Profiling, and Liposomes of sp. Crude Extract Supported by in silico Analysis.

Int J Nanomedicine 2021 4;16:3861-3874. Epub 2021 Jun 4.

Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.

Introduction: Sponge- sp. (Family: Spongiidae) is a coastal sponge that possesses a broad variety of natural-products. However, the exact chemical constituents and cytotoxic activity of the extract are still undefinable.

Methodology: In the present study, the metabolomic profiling of sp. dereplicated 20 compounds, utilizing liquid chromatography coupled with high-resolution mass spectrometry (LC-HRESIMS). derived crude extract, before and after encapsulation within nanosized liposomes, was in vitro screened against hepatic, breast, and colorectal carcinoma human cell lines (HepG2, MCF-7, and Caco-2, respectively).

Results: The identified metabolites were fit to diverse chemical classes, covering diterpenes, an indole alkaloid, sesterterpenoid, sterol, and methylherbipoline salt. Comprehensive in silico experiments predicted several compounds in the sponge-derived extract (eg, compounds -) to have an anticancer potential via targeting multiple targets. The crude extract showed moderate antiproliferative activities towards studied cell lines with IC values range from 10.7 to 12.4 µg/mL. The formulated extract-containing liposomes (size 141±12.3nm, PDI 0.222, zeta potential 20.8 ± 2.3), significantly enhanced the in vitro anticancer activity of the entrapped extract (IC values ranged from 1.7 to 4.1 µg/mL).

Discussion: Encapsulation of both the hydrophilic and the lipophilic components of the extract within the lipid-based nanovesicles enhanced the cellular uptake and accessibility of the entrapped cargo. This study introduces liposomal nano-vesicles as a promising approach to improve the therapeutic potential of sponge-derived extracts.
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http://dx.doi.org/10.2147/IJN.S310720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187037PMC
June 2021

Novel Phenolic Compounds as Potential Dual EGFR and COX-2 Inhibitors: Design, Semisynthesis, in vitro Biological Evaluation and in silico Insights.

Drug Des Devel Ther 2021 31;15:2325-2337. Epub 2021 May 31.

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia.

Introduction: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance.

Methods: Three semi-synthetic series of compounds (, , and ) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of L. (-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities.

Results: Compounds and showed superior inhibitory activity against EGFR (IC: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds and exhibited the highest cytotoxic activity with average IC values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites.

Discussion: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.
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http://dx.doi.org/10.2147/DDDT.S310820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178614PMC
May 2021

Bioactive Apigenin loaded oral nano bilosomes: Formulation optimization to preclinical assessment.

Saudi Pharm J 2021 Mar 22;29(3):269-279. Epub 2021 Feb 22.

Department of Pharmaceutics and Ind. Pharmacy, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt.

Aim: Diabetic (type-2) is a metabolic disease characterized by increased blood glucose level from the normal level. In the present study, apigenin (AG) loaded lipid vesicles (bilosomes: BIL) was prepared, optimized and evaluated for the oral therapeutic efficacy.

Experimental: AG-BIL was prepared by a thin-film evaporation method using cholesterol, span 60 and sodium deoxycholate. The prepared formulation was optimized by 3-factor and 3-level Box-Behnken design using particle size, entrapment efficiency and drug release as a response. The selected formulation further evaluated for  permeation,  pharmacokinetic and pharmacodynamics study.

Results: The optimized AG bilosomes (AG-BILopt) has shown the vesicle size 183.25 ± 2.43 nm, entrapment efficiency 81.67 ± 4.87%. TEM image showed a spherical shape vesicle with sharp boundaries. The drug release study revealed a significant enhancement in AG release (79.45 ± 4.18%) from AG-BILopt as compared to free AG-dispersion (25.47 ± 3.64%). The permeation and pharmacokinetic studies result revealed 4.49 times higher flux and 4.67 folds higher AUC than free AG-dispersion. The antidiabetic activity results showed significant (P < 0.05) enhancement in therapeutic efficacy than free AG-dispersion. The results also showed marked improvement in biochemical parameters.

Conclusion: Our findings suggested, the prepared apigenin loaded bilosomes was found to be an efficient delivery in the therapeutic efficacy in diabetes.
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http://dx.doi.org/10.1016/j.jsps.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085606PMC
March 2021

Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown Algae : An In-Silico-Supported In-Vitro Study.

Antibiotics (Basel) 2021 Apr 10;10(4). Epub 2021 Apr 10.

Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae "Sargassaceae" dereplicated eleven compounds -. Further phytochemical investigation afforded two new aryl cresol -, along with eight known compounds -. Both new metabolites, along with showed moderate in vitro antiproliferative activity against HepG2, MCF-7, and Caco-2. Pharmacophore-based virtual screening suggested both 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The in vitro enzyme assays revealed and were able to inhibit 5-LOX more preferentially than 15-LOX, while showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico investigation revealed the molecular interactions inside both enzymes' active sites and explained the varying inhibitory activity for and toward 5-LOX and 15-LOX.
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http://dx.doi.org/10.3390/antibiotics10040416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069941PMC
April 2021

Methanolic extract of Cucumis melo attenuates ethylene glycol-induced nephrolithiasis in Wistar rats.

Urolithiasis 2021 Aug 9;49(4):301-308. Epub 2021 Apr 9.

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Evaluation of the effects of methanolic extract of Cucumis melo in ethylene glycol-induced nephrolithiasis on Wistar rats. 0.75% solution of ethylene glycol (EG) in payable water was given to produce nephrolithiasis on Wistar rats. The action of oral intake of methanolic extract of Cucumis melo seed in nephrolithiasis is studied and is matched with the action of oral intake of Cystone (standard) on Wistar rats. EG resulted in hyperoxaluria and deposition of calcium oxalate as well as raised urinary excretion of oxalate and calcium. Supplementation with methanolic extract of Cucumis melo seed decreased the increased renal oxalate, indicating a regulatory effect on oxalate formation endogenously. The outcomes stipulate that the seed of Cucumis melo is endowed with antinephrolithiatic action.
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http://dx.doi.org/10.1007/s00240-021-01263-5DOI Listing
August 2021

New Cytotoxic Natural Products from the Red Sea Sponge .

Mar Drugs 2020 May 3;18(5). Epub 2020 May 3.

Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, New Minia 61111, Egypt.

Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (), and a cerebroside, stylissoside A (), from the methanol extract of the Red Sea sponge . Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract's metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, and , displayed strong cytotoxicity against the MCF-7 cell line, with IC values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC at 36.8 ± 0.16 µM for and IC 30.5 ± 0.23 µM for compared to the standard drug cisplatin. Molecular docking experiments showed that and displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.
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http://dx.doi.org/10.3390/md18050241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281077PMC
May 2020

Sulfonamide-based 4-anilinoquinoline derivatives as novel dual Aurora kinase (AURKA/B) inhibitors: Synthesis, biological evaluation and in silico insights.

Bioorg Med Chem 2020 07 25;28(13):115525. Epub 2020 Apr 25.

Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf 72341, Saudi Arabia; Department of Pharmaceutical Organic Chemistry, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address:

Aurora kinases (AURKs) were identified as promising druggable targets for targeted cancer therapy. Aiming at the development of novel chemotype of dual AURKA/B inhibitors, herein we report the design and synthesis of three series of 4-anilinoquinoline derivatives bearing a sulfonamide moiety (5a-d, 9a-d and 11a-d). The % inhibition of AURKA/B was determined for all target quinolines, then compounds showed more than 50% inhibition on either of the enzymes, were evaluated further for their IC on the corresponding enzyme. In particular, compound 9d displayed potent AURKA/B inhibitory activities with IC of 0.93 and 0.09 µM, respectively. Also, 9d emerged as the most efficient anti-proliferative analogue in the US-NCI anticancer assay toward the NCI 60 cell lines panel, with broad spectrum activity against different cell lines from diverse cancer subpanels. Docking studies, confirmed that, the sulfonamide SO oxygen was involved in a hydrogen bond with Lys162 and Lys122 in AURKA and AURKB, respectively, whereas, the sulfonamide NH could catch hydrogen bond interaction with the surrounding amino acid residues Lys141, Glu260, and Asn261 in AURKA and Lys101, Glu177, and Asp234 in AURKB. Furthermore, N1 nitrogen of the quinoline scaffold formed an essential hydrogen bond with the hinge region key amino acids Ala213 and Ala173 in AURKA and AURKB, respectively.
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http://dx.doi.org/10.1016/j.bmc.2020.115525DOI Listing
July 2020
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