ORCID Profile
0000-0003-1348-6567
Current Organisations
College of Pharmacy, Umm Al-Qura University
,
Institute of Astronomy and Astrophysics Academia Sinica
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Publisher: Informa UK Limited
Date: 26-05-2022
DOI: 10.1080/13543776.2022.2078193
Abstract: The success of the CDK4/6 inhibitor Ibrance™ (Palbociclib) as an anticancer agent inspired and directed more efforts toward the discovery of selective cyclin-dependent kinase (CDKs) inhibitors. CDK2 is a member of the CDKs family that plays an important role in regulating the progression of cells into both S- and M-phases of the cell cycle. Studies suggest that overexpression of CDK2 may be implicated in tumor growth in cancer. This review covers the patent literature of CDK2 inhibitors published between 2017 and 2021. We searched the online databases of the European Patent Office, American Chemical Society, and Google patents. Developing selective CDK2 inhibitors is challenging due to the absence of a previously approved selective CDK2 inhibitor. However, ongoing efforts by Incyte Corporation and Pfizer Inc., which are reported herein, may stand out as a new starting point and bring novel information critical for the medicinal chemistry and drug design scientists in the field of CDK2 inhibitors' development.
Publisher: MDPI AG
Date: 13-10-2022
Abstract: In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 Mpro. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC50). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC50 value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC50 values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 Mpro enzyme was investigated by utilizing the SARS-CoV-2 Mpro assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 Mpro inhibitory potential was attained for fondaparinux sodium with an IC50 value of 2.36 µM, surpassing the reference tipranavir (IC50 = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 Mpro inhibitory potential was attained for dabigatran with an IC50 value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches.
Publisher: MDPI AG
Date: 28-02-2022
Abstract: (1) Background: Pneumocystis jirovecii pneumonia (PCP) has a substantial impact on the morbidity and mortality of patients, especially those with autoimmune disorders, thus requiring optimal dosing strategies of Trimethoprim–Sulfamethoxazole (TMP-SMX). Therefore, to ensure the safety of TMP-SMX, there is a high demand to review current evidence in PCP patients with a focus on dose optimization strategies (2) Methods: Various databases were searched from January 2000 to December 2021 for articles in English, focusing on the dose optimization of TMP-SMX. The data were collected in a specific form with predefined inclusion and exclusion criteria. The quality of each article was evaluated using a Newcastle–Ottawa Scale (NOS) for retrospective studies, Joanna Briggs Institute (JBI) critical checklist for case reports, and Cochrane bias tool for randomized clinical trials (RCTs) (3) Results: Thirteen studies met the inclusion criteria for final analysis. Of the 13 selected studies, nine were retrospective cohort studies, two case reports, and two randomized controlled trials (RCT). Most of the studies compared the high-dose with low-dose TMP-SMX therapy for PCP. We have found that a low dose of TMP-SMX provides satisfactory outcomes while reducing the mortality rate and PCP-associated adverse events. This strategy reduces the economic burden of illness and enhances patients’ compliance to daily regimen plan (4) Conclusions: The large-scale RCTs and cohort studies are required to improve dosing strategies to prevent initial occurrence of PCP or to prevent recurrence of PCP in immune compromised patients.
Publisher: Oxford University Press (OUP)
Date: 26-04-2016
DOI: 10.1093/PASJ/PSW029
Publisher: Springer Science and Business Media LLC
Date: 30-05-2023
DOI: 10.1007/S10658-023-02684-1
Abstract: Three concentrations (1.25, 2.5, and 5 × 10 7 spores ml −1 ) (of the biocontrol fungus Purpureocillium lilacinum (strain AUMC 10620) were tested on citrus nematode Tylenchulus semipenetrans under in vitro and field conditions. Larvae and eggs were exposed to the fungal spores in vitro for 24, 48, and 72 h, and the findings were recorded at each time point. These results were compared with the application of the nematicide abamectin. Strain AUMC 10620 effectively reduced larval activity and egg hatching of T. semipenetrans under laboratory conditions. The highest concentration (5× 10 7 spores ml −1 ) of P. lilacinum , resulted in 89.01% immobility in the larvae, compared to abamectin, which resulted in 65.93% immobility after 48 h of exposure. These percentages of immobility were increased after 72 h of exposure (100 and 85.09%) when P. lilacinum at a concentration of 5 × 10 7 spores ml −1 and abamectin were used, respectively. On the other hand, the two other P. lilacinum concentrations (1.25, and 2.5 × 10 7 spores ml −1 ) affected the T. semipenetrans larvae to a lesser extent. The highest fungal concentration 5× 10 7 spores ml −1 inhibited the hatching of T. semipenetrans eggs in vitro with 71.34, 80, and 86.67% after 24, 48 and 72 h of treatment compared to the abamectin treatment which showed 76.67, 78, and 87% after the abovementioned periods, respectively. In addition, the application of P. lilacinum (5 × 10 7 spores ml −1 ) or abamectin under field conditions significantly ( P 0.05) reduced the population of the major nematode species ( T. semipenetrans, Tylenchorhynchus spp., Helicotylenchus spp., and Pratylenchus spp.) infesting citrus after one, two, and three weeks of treatment compared to the control treatment but with no significant ( P 0.05) differences between the two treatments. Three weeks after the field application, the percentage of nematode reduction was significantly ( P 0.05) smaller than the control treatment at concentrations of 5, 2.5, and 1.25 × 10 7 spores ml −1 , respectively, by 78.42, 64.03, and 58.35%. It is evident from these results that the application of P. lilacinum strain (AUMC 10620) can be used in integrated pest management programs to control nematodes infesting citrus trees. Graphical abstract
Publisher: MDPI AG
Date: 16-06-2022
DOI: 10.3390/PHARMACEUTICS14061279
Abstract: Icariin (ICA), a main active compound of the Epimedium genus, is used as an aphrodisiac in traditional Chinese herbal medicine. Despite its therapeutic efficacy, ICA displays reduced oral absorption, and therefore, low bioavailability hindered its clinical application. Implementing nanotechnology in the field of formulation has been a focus to improve the efficacy of ICA. In this regard, polymeric nanoparticles find a potential application as drug delivery systems. A nanosphere formula was designed, aiming to improve the drug’s efficacy. The proposed ICA nanosphere formula (tocozeinolate) was optimized using D-optimal response surface design. The concentrations of ICA (X1), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS, X2), zein (X3), and sodium deoxycholate (SDC, X4) expressed as percentages were investigated as quantitative independent variables. As per the experimental design, 23 formulations were developed, which were investigated for particle size (PS, nm), zeta potential (ZP, mV), and entrapment efficiency (EE, %) as response parameters. Numerical optimization and desirability approach were employed to predict the optimized variable levels that, upon combination, could result in minimized size and maximized zeta potential and ICA entrapment. The optimized ICA–tocozeinolate nanospheres showed a particle size of 224.45 nm, zeta potential of 0.961 mV, and drug entrapment of 65.29% that coincide well with the predicted values. The optimized ICA–tocozeinolate nanospheres were evaluated for sexual behavior in Wistar male rats compared to raw ICA at equivalent doses (20 mg/kg). In vivo assessment results showed significant sexual behavior enhancement by the optimized formulation, as evidenced by decreased average time of both mount latency (ML) and ejaculation latency (EL) to almost half those of raw ICA. Additionally, intromission latency (IL) time was reduced by 41% compared to the raw ICA. These results highlighted the potential of the proposed ICA–tocozeinolate nanospheres as a promising platform for improving the delivery and efficacy of therapeutic agents.
Publisher: Oxford University Press (OUP)
Date: 23-06-2015
DOI: 10.1093/PASJ/PSV044
Publisher: Oxford University Press (OUP)
Date: 25-05-2016
DOI: 10.1093/PASJ/PSW043
Publisher: Oxford University Press (OUP)
Date: 14-04-2018
DOI: 10.1093/PASJ/PSY030
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 02-2012
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2RA04385H
Abstract: As promising antimicrobials against MDR pathogens, two novel series of isatin thiazolyl-pyrazoline conjugates were developed. Compounds 9f and 10h were the most effective against the tested MDR strains.
Publisher: MDPI AG
Date: 18-10-2022
DOI: 10.3390/MOLECULES27207020
Abstract: Aphthous ulcers are very common disorders among different age groups and are very noxious and painful. The incidence of aphthous ulcer recurrence is very high and it may even last for a maximum of 6 days and usually, patients cannot stand its pain. This study aims to prepare a buccoadhesive fast dissolving film containing Corchorus olitorius seed extract to treat recurrent minor aphthous ulceration (RMAU) in addition to clinical experiments on human volunteers. An excision wound model was used to assess the in vivo wound healing potential of Corchorus olitorius L. seed extract, with a focus on wound healing molecular targets such as TGF-, TNF-, and IL-1. In addition, metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds was explored. Moreover, molecular docking experiments were performed to elucidate the binding confirmation of the isolated compounds with three molecular targets (TNF-α, IL-1β, and GSK3). Additionally, the in vitro antioxidant potential of C. olitorius seed extract using both H2O2 and superoxide radical scavenging activity was examined. Clinical experiments on human volunteers revealed the efficiency of the prepared C. olitorius seeds buccal fast dissolving film (CoBFDF) in relieving pain and wound healing of RMAU. Moreover, the wound healing results revealed that C. olitorius seed extract enhanced wound closure rates (p ≤ 0.001), elevated TGF-β levels and significantly downregulated TNF-α and IL-1β in comparison to the Mebo-treated group. The phenotypical results were supported by biochemical and histopathological findings, while metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds yielded a total of 21 compounds belonging to erse chemical classes. Finally, this study highlights the potential of C. olitorius seed extract in wound repair uncovering the most probable mechanisms of action using in silico analysis.
Publisher: Informa UK Limited
Date: 26-04-2022
Location: Taiwan, Province of China
No related grants have been discovered for Mohammed Abourehab.