Publications by authors named "Arafa Musa"

9 Publications

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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

Olive Oil/Pluronic Oleogels for Skin Delivery of Quercetin: In Vitro Characterization and Ex Vivo Skin Permeability.

Polymers (Basel) 2021 May 31;13(11). Epub 2021 May 31.

Department of Pharmaceutics, Faculty of Pharmacy, Ahram Canadian University, Giza 14756, Egypt.

The main objective of this study was to prepare and characterize oleogel as potential carrier for quercetin skin delivery. The formulations were prepared by adding olive oil (5-30%) to Pluronic F127 hydrogel and were evaluated for particle size, zeta potential, viscosity in vitro quercetin release and stability, and were compared with that of Pluronic F127 hydrogel. The selected formulation was characterized for its interaction possibility, ex vivo skin permeation and skin histological changes and safety. The particle sizes ranged from 345.3 ± 5.3 nm to 401.5 ± 2.8 nm, and possessed negative charges. The viscosities of the formulations were found in the range of 6367-4823 cps with inverse proportionality to olive oil percentage while the higher percentages showed higher quercetin release. Percentages of 25% and 30% olive oil showed instability pattern under the conditions of accelerated stability studies. Differential scanning calorimetry verified the existence of quercetin in micellar aggregation and the network in the case of hydrogel and oleogel respectively. Ex vivo skin permeation showed an improved skin permeation of quercetin when 20% olive oil containing oleogel was used. Skin histology after 10 days of application showed stratum corneum disruption and good safety profile. Based on these findings, the proposed oleogel containing 20% olive oil denotes a potential carrier for topical delivery of quercetin.
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http://dx.doi.org/10.3390/polym13111808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198417PMC
May 2021

Antiulcer Potential of L. cv. Arbequina Leaf Extract Supported by Metabolic Profiling and Molecular Docking.

Antioxidants (Basel) 2021 Apr 22;10(5). Epub 2021 Apr 22.

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

Gastric ulceration is among the most serious humanpublic health problems. L. cv. Arbequina is one of the numerous olive varieties which have scarcely been studied. The reported antioxidant and anti-inflammatory potential of the olive plant make it a potential prophylactic natural product against gastric ulcers. Consequently, the main goal of this study is to investigate the gastroprotective effect of L. cv. Arbequina leaf extract. LC-HRMS-based metabolic profiling of the alcoholic extract of L. cv. Arbequina led to the dereplication of 18 putative compounds (-). In vivo indomethacin-induced gastric ulcer in a rat model was established and the extract was tested at a dose of 300 mg kg compared to cimetidine (100 mg kg). The assessment of gastric mucosal lesions and histopathology of gastric tissue was done. It has been proved that significantly decreased the ulcer index and protected the mucosa from lesions. The antioxidant potential of the extract was evaluated using three in vitro assays, HO scavenging, xanthine oxidase inhibitory, and superoxide radical scavenging activities and showed promising activities. Moreover, an in silico based study was performed on the putatively dereplicated compounds, which highlighted that 3-hydroxy tyrosol () and oleacein () can target the 5-lipoxygenase enzyme (5-LOX) as a protective mechanism against the pathogenesis of ulceration. Upon experimental validation, both compounds 3-hydroxy tyrosol (HT) and oleacein (OC) ( and , respectively) exhibited a significant in vitro 5-LOX inhibitory activity with IC values of 8.6 and 5.8 µg/mL, respectively. The present study suggested a possible implication of leaves as a potential candidate having gastroprotective, antioxidant, and 5-LOX inhibitory activity for the management of gastric ulcers.
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http://dx.doi.org/10.3390/antiox10050644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146603PMC
April 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

Morpholine-based chalcones as dual-acting monoamine oxidase-B and acetylcholinesterase inhibitors: synthesis and biochemical investigations.

J Enzyme Inhib Med Chem 2021 Dec;36(1):188-197

Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon, Republic of Korea.

Nine compounds () containing the morpholine moiety were assessed for their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE). Most of the compounds potently inhibited MAO-B; most potently inhibited with an IC value of 0.030 µM, followed by (0.25 µM). most potently inhibited AChE (IC = 6.1 µM), followed by (IC = 12.01 µM) and most potently inhibited MAO-A (IC = 7.1 µM). was a reversible mixed-type inhibitor of MAO-B ( = 0.018 µM); reversibly competitively inhibited AChE ( = 2.52 µM); and reversibly noncompetitively inhibited AChE ( = 7.04 µM). , and crossed the blood-brain barrier, and were non-toxic to normal VERO cells. These results show that is a selective inhibitor of MAO-B and that is a dual-acting inhibitor of AChE and MAO-B, and that both should be considered candidates for the treatment of Alzheimer's disease.
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http://dx.doi.org/10.1080/14756366.2020.1842390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808749PMC
December 2021

Enhanced full-thickness wound healing via extract delivery based on a chitosan/gelatin dressing incorporating microemulsion.

Drug Dev Ind Pharm 2021 Feb 4;47(2):215-224. Epub 2021 Jan 4.

Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia.

There are many synthetic drugs in literature have been utilized in healing of the wounds although the natural product specially antioxidants can offer similar if not better biological activity in that regard. Genus Sophora is well known to contain flavonoids and phenolic compounds which have antioxidant and inflammatory effects. So, the aim of the current study was to develop and evaluate chitosan/gelatin based extract-loaded microemulsion as wound dressing. extract (SGE) contained 16 major compounds which have reasonable antioxidant activity. The developed microemulsion showed that Tween 80 produced significant ( < 0.05) lower particle size than Pluronic F127 at the same SGE concentration whereas high concentration of extract results in large particle size. Thermodynamic stability studies showed that using higher concentration of the extract produced less stable formulations. The selected formulation was impregnated in the dressing base (chitosan/gelatin; 2:1 w/w ratio) which exhibited more water absorption. evaluation revealed that the dressing displayed superior wound repair compared to the control in terms histological examination and determination of alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA). Thus, SGE-loaded microemulsion-impregnated gelatin/chitosan could be a potential candidate for the wound healing.
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http://dx.doi.org/10.1080/03639045.2020.1863420DOI Listing
February 2021

Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors.

Molecules 2020 Nov 17;25(22). Epub 2020 Nov 17.

Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Korea.

Twelve pyridazinones (-) containing the (2-fluorophenyl) piperazine moiety were designed, synthesized, and evaluated for monoamine oxidase (MAO) -A and -B inhibitory activities. was found to be the most potent MAO-B inhibitor with an IC value of 0.013 µM, followed by (IC = 0.039 µM). Inhibitory potency for MAO-B was more enhanced by bromo substitution () than by bromo substitution (). For substitution, inhibitory potencies for MAO-B were as follows: -Cl () > -N(CH) () > -OCH () > Br () > F () > -CH () > -H (). and efficiently inhibited MAO-A with IC values of 1.57 and 4.19 µM and had the highest selectivity indices (SIs) for MAO-B (120.8 and 107.4, respectively). and were found to be reversible and competitive inhibitors of MAO-B with K values of 0.014 and 0.0071, respectively. Moreover, was less toxic to healthy fibroblast cells (L929) than . Molecular docking simulations with MAO binding sites returned higher docking scores for and with MAO-B than with MAO-A. These results suggest that and are selective, reversible, and competitive inhibitors of MAO-B and should be considered lead candidates for the treatment of neurodegenerative disorders like Alzheimer's disease.
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http://dx.doi.org/10.3390/molecules25225371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698448PMC
November 2020

An Agathokakological Tale of Δ-THC: Exploration of Possible Biological Targets.

Curr Drug Targets 2021 ;22(7):823-834

Department of Pharmaceutical Chemistry, National College of Pharmacy, Calicut, India.

Δ-Tetrahydrocannabinol (Δ-THC), the active phytocannabinoid in cannabis, is virtually an adjunct to the endogenous endocannabinoid signaling system. By interacting with G-proteincoupled receptors CB1 and CB2, Δ-THC affects peripheral and central circulation by lowering sympathetic activity, altering gene expression, cell proliferation, and differentiation, decreasing leukocyte migration, modulating neurotransmitter release, thereby modulating cardiovascular functioning, tumorigenesis, immune responses, behavioral and locomotory activities. Δ-THC effectively suppresses chemotherapy-induced vomiting, retards malignant tumor growth, inhibits metastasis, and promotes apoptosis. Other mechanisms involved are targeting cell cycle at the G2-M phase in human breast cancer, downregulation of E2F transcription factor 1 (E2F1) in human glioblastoma multiforme, and stimulation of ER stress-induced autophagy. Δ-THC also plays a role in ameliorating neuroinflammation, excitotoxicity, neuroplasticity, trauma, and stroke and is associated with reliving childhood epilepsy, brain trauma, and neurodegenerative diseases. Δ-THC via CB1 receptors affects nociception, emotion, memory, and reduces neuronal excitability and excitotoxicity in epilepsy. It also increases renal blood flow, reduces intraocular pressure via a sympathetic pathway, and modulates hormonal release, thereby decreasing the reproductive function and increasing glucose metabolism. Versatile medical marijuana has stimulated abundant research demonstrating substantial therapeutic promise, suggesting the possibilities of first-in-class drugs in diverse therapeutic segments. This review represents the current pharmacological status of the phytocannabinoid, Δ-THC, and synthetic analogs in cancer, cardiovascular, and neurodegenerative disorders.
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http://dx.doi.org/10.2174/1389450121666201001123515DOI Listing
January 2021
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