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Cancer remains the leading cause of death in the world despite the significant advancements made in anticancer drug discovery. This study is aimed to computationally evaluate the efficacy of 63 in-house synthesized pyrazole derivatives targeted to bind with prominent cancer targets namely EGFR, RSK1, RAF1, PARP2 and LIN28B known to be expressed, respectively, in lung, colon, skin, ovarian and pancreatic cancer cells. Initially, we perform the molecular docking investigations for all pyrazole compounds with a comparison to known standard drugs for each target. Docking studies have revealed that some pyrazole compounds possess better binding affinity scores than standard drug compounds. Thereafter, a long-range of 1 μs molecular dynamic (MD) simulation study for top ranked docked compounds with all respective proteins was carried out to assess the interaction stability in a dynamic environment. The results suggested that the top ranked complexes showed a stable interaction profile for a longer period of time. The outcome of this study suggests that pyrazole compounds, M33, M36, M76 and M77, are promising molecular candidates that can modulate the studied target proteins significantly in comparison to their known inhibitor based on their selective binding interactions profile. Furthermore, ADME-T profile has been explored to check for the drug-likeness and pharmacokinetics profiles and found that all proposed compounds exhibited acceptable values for being a potential drug-like candidate with non-toxic characteristics. Overall, extensive computational investigations indicate that the four proposed pyrazole inhibitors/modulators studied against each respective target protein will be helpful for future cancer therapeutic developments.Communicated by Ramaswamy H. Sarma.

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine., Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves., Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration., Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future., Competing Interests: CONFLICT OF INTEREST The authors declare that they have no conflicts of interest., (© 2023 Korean Pharmacopuncture Institute.)

Microbial infections remain a worldwide leading cause of death, despite the evolution of a large number of new antibiotics every year. Currently, several bacteria have developed resistance against antibiotics drugs which remain a major issue in antibiotics drug discovery. This review provides detailed information about antimicrobial and antifungal agent synthesis belonging to the pyrazoles scaffold. We reassemble the results obtained from several studies to characterize the importance of heteroatom nuclei in many synthetic products. Additionally, several compounds based on pyrazole derivatives such as benzimidazole, benzothiazole, indole, acridine, oxadiazole, imidazole, isoxazole, pyrazole, triazole, quinoline and quinazoline including other pyrazole containing drugs such as pyridazine, pyridine and pyrimidine are highlighted. Furthermore, you will find in this review 134 best promise structures collected from recent studies, relating the pyrazoles structures to the relevant biological activities, in particular, antimicrobial and antifungal one., Competing Interests: The Authors declare that no competing interest exists., (Copyright © 2022 by West African Journal of Medicine.)

Despite continual efforts being made with multiple clinical studies and deploying cutting-edge diagnostic tools and technologies, the discovery of new cancer therapies remains of severe worldwide concern. Multiple drug resistance has also emerged in several cancer cell types, leaving them unresponsive to the many cancer treatments. Such a condition always prompts the development of next-generation cancer therapies that have a better chance of inhibiting selective target macromolecules with less toxicity. Therefore, in the present study, extensive computational approaches were implemented combining molecular docking and dynamic simulation studies for identifying potent pyrazole-based inhibitors or modulators for CRMP2, C-RAF, CYP17, c-KIT, VEGFR, and HDAC proteins. All of these proteins are in some way linked to the development of numerous forms of cancer, including breast, liver, prostate, kidney, and stomach cancers. In order to identify potential compounds, 63 in-house synthesized pyrazole-derivative compounds were docked with each selected protein. In addition, single or multiple standard drug compounds of each protein were also considered for docking analyses and their results used for comparison purposes. Afterward, based on the binding affinity and interaction profile of pyrazole compounds of each protein, potentially strong compounds were filtered out and further subjected to 1000 ns MD simulation analyses. Analyzing parameters such as RMSD, RMSF, RoG and protein-ligand contact maps were derived from trajectories of simulated protein-ligand complexes. All these parameters turned out to be satisfactory and within the acceptable range to support the structural integrity and interaction stability of the protein-ligand complexes in dynamic state. Comprehensive computational analyses suggested that a few identified pyrazole compounds, such as M33, M36, M72, and M76, could be potential inhibitors or modulators for HDAC, C-RAF, CYP72 and VEGFR proteins, respectively. Another pyrazole compound, M74, turned out to be a very promising dual inhibitor/modulator for CRMP2 and c-KIT proteins. However, more extensive study may be required for further optimization of the selected chemical framework of pyrazole derivatives to yield improved inhibitory activity against each studied protein receptor.

Erodium guttatum is widely used in folk medicine in many countries to treat various ailments such as urinary inflammation, diabetes, constipation, and eczema. The aim of this study is the determination of mineral and phenolic compounds of E. guttatum extracts as well as the investigation of their antidiabetic and antioxidant properties. The mineral composition was determined by the methods of inductively coupled plasma atomic emission spectroscopy analysis. Phytochemical contents of total polyphenols, total flavonoids, and catechic tannins were estimated by colorimetric dosages. The phenolic composition was identified by high-resolution mass spectrometry (HRMS) analysis. The antioxidant activity of E. guttatum extracts was measured in vitro by five methods (DPPH, ABTS, FRAP, H 2 O 2 , and xanthine oxidase) and in vivo by assaying the malondialdehyde marker (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). The obtained results showed that the root plant material is rich in minerals such as k, Ca, and Mg. The methanolic extract of E. guttatum is the richest in polyphenols (389.20 ± 1.55 mg EAG/gE), tannins (289.70 ± 3.57 mg EC/gE), and flavonoids (432.5 ± 3.21 mg ER/gE). Concerning the ESI-HRMS analysis, it showed the presence of numerous bioactive compounds, including shikimic acid, rottlerine, gallic acid, and vanillic acid. Moreover, the aqueous and alcoholic extracts of E. guttatum exhibited antiradical and antioxidant activity in five tests used, with the best effect of the methanolic extract. Moreover, findings showed that in vivo investigations confirmed those obtained in vitro. On the other hand, E. guttatum showed important antidiabetic effects in vivo . Indeed, diabetic mice treated with extracts of E. guttatum were able to significantly reduce MDA levels and increase the secretion of enzymatic and nonenzymatic antioxidants (SOD, CAT, and GSH, respectively). However, the antioxidant activity of the extracts might be attributed to the abundance of bioactive molecules; as results, this work serves as a foundation for additional pharmacological research., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Kaoutar Benrahou et al.)

Despite the decades of scientific studies for developing promising new therapies, cancer remains a major cause of illness and mortality, worldwide. Several cancer types are the major topic of research in drug discovery programs due to their global incidence cases and growing frequency. In the present study, using two different statistical approaches PCA (principal component analysis) and PLS (partial least squares), six 2D-QSAR (quantitative structure activity relationship) models have been developed for the set of compounds retrieved against seven cancer cell lines vizPC-3, B16F10, K562, MDA-MB-231, A2780, and ACHN. For the creation and validation of 2D-QSAR models, OECD (Organization for Economic Co-operation and Development) requirements have been strictly followed. All of the generated 2D-QSAR models produce a significant and high correlation coefficient value with several other statistical parameters. Moreover, developed 2D-QSAR models have been used for activity predictions of in-house synthesized 63 pyrazole derivatives compounds. Precisely, most statistically significant and accepted2D-QSAR model generated for each cancer cell line has been used to predict the pIC 50 value (anti-cancer activity) of all 63 synthesized pyrazole derivatives. Furthermore, designing of novel pyrazole derivatives has been carried out by substituting the essential functional groups based on the best derived 2D-QSAR models for each cancer cell line, more precisely, based on the most significant molecular descriptors with enhanced anti-cancer activity. Finally, the prediction of the new designed molecules reveals higher pIC 50 than the standard compounds., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Ltd.)

Moroccan folk healers use medicinal plants to treat several diseases including skin burns. The traditional knowledge of wound healing is not common among the general population. Only one ethnobotanical survey was carried out in Rabat, Morocco, to track the traditional use of medicinal plants in wound healing. Therefore, our report aimed to study the medicinal plants used in Taza region to treat wound healing. In total, 218 individuals participated in this survey. More than 40 medicinal plants belonging to 30 botanical families were cited as anti-burn remedies. The most commonly used medicinal plants were Agave sisalana L., Nerium oleander L., Tetraclinis articulata Benth., Lawsonia inermis L., Artemisia herba-alba Asso., and Trigonella foenum-graecum L. Most of the used medicinal plants belong to Asteraceae family. Comparing our results with the previous survey, we noted that twelve plants were reported for the first time as wound healing agents. The ethnomedicinal use showed that plants leaves are the most commonly used parts. Pulverization was the selected method of preparation. The direct application of powder to the burns was the most common way of treatment. Our study revealed, for the first time, the importance of medicinal plants to treat skin burns in Taza region. Our results could be considered as the stepping stone for creating a database of wound healing medicinal plants to promote scientific studies on these plants revealing their constituents and side effects., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Hanae Naceiri Mrabti et al.)

Thymus broussonetii Boiss ( T. broussonetii ) is a rare medicinal and aromatic plant. It is widely used in traditional medicine to treat several diseases, including diarrhea, fever, cough, irritation, skin diseases, rheumatism, respiratory ailments, influenza, and digestion problems. In this review, we have critically summarized previous data on T. broussonetii about its phytochemistry, botanical and geographical distribution, toxicological investigation, and pharmacological properties. Using scientific research databases such as Wiley Online, SciFinder, ScienceDirect, PubMed, SpringerLink, Web of Science, Scopus Wiley Online, and Google Scholar, the data on T. broussonetii were collected and discussed. The presented data regrouped bioactive compounds and biological activities of T. broussonetii . The findings of this work showed that essential oils and extracts of T. broussonetii exhibited numerous pharmacological activities ( in vitro and in vivo ), particularly antibacterial, antifungal, antioxidant, anticancer, anti-inflammatory, insecticidal, antipyretic, antinociceptive, and immunological and behavioral effects. While toxicological studies of T. broussonetii essential oils and extracts are lacking, modern scientific tools revealed the presence of different classes of secondary metabolites such as terpenoids, alkaloids, flavonoids, tannins, coumarins, quinones, carotenoids, and steroids. T. broussonetii essential oils, especially from the aerial parts, exhibited potent antibacterial, antifungal, and antioxidant effects. An in-depth toxicological investigation is needed to validate the efficacy and safety of T. broussonetii extracts and essential oils and their secondary metabolites. However, further pharmacokinetic and pharmacodynamic studies should be performed to validate its bioavailability., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Hanae Naceiri Mrabti et al.)

Type 2 diabetes is one of the noncommunicable diseases that is becoming a pandemic in Africa. In Morocco, traditional healers have started to use herbal medicines for the treatment of diabetes either individually or in combination with food. The current study aimed to perform an ethnobiological survey of antidiabetic plants use in the Taza region of Morocco. A total of 193 traditional healers were interviewed using a semistructured questionnaire. Data collected were analyzed utilizing the use value (UV), fidelity level (FL), and relative frequency citation (RFC) indices. Forty-six plant species belonging to 28 families were recorded for the treatment of diabetes in the Taza region of Morocco. The most frequently cited plant species are Salvia officinalis , Marrubium vulgare , and Ajuga iva. Lamiaceae, Asteraceae, and Fabaceae were the most reported families. Leaves are the most used part of plants to prepare drugs, the decoction is the preferred mode of preparation, and remedies are often administered orally. Interestingly, Cytisus battandieri, Urginea maritima, Plantago ovata, and Ziziphus jujuba were reported as new medicinal plants used to treat diabetes in the Taza region of Morocco. People in the Taza region still rely on indigenous plants for their basic healthcare needs. Further research should be carried out to validate the antidiabetic effect of the newly reported plant species. This validation can be investigated by the determination of bioactive compounds and evaluation of their in vitro and in vivo antidiabetic effects., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Hanae Naceiri Mrabti et al.)

Pyrazole is a five-membered aromatic heterocyclic ring with two adjacent nitrogen atoms C 3 H 3 N 2 H.The presence of this nucleus in pharmacological agents of various therapeutic categories gifts a broad spectrum of biological activities and pharmaceuticals that contain pyrazole like celecoxib (anti-inflammatory), CDPPB (antipsychotic), Rimonabant (anti-obesity), Difenamizole, (Analgesic), Betazole (H2 receptor agonist), Fezolamide (Antidepressant), etc… The pharmacological potential of the pyrazole fraction is proved in many publication where they synthesized and evaluated pyrazoles against several biological agents. The aim of this article review is to survey recent works linking pyrazole structures to anticancer activities corresponding to 9 different type of cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)