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The discovery and development of new potent antimicrobial and antioxidant agents is an essential lever to protect living beings against pathogenic microorganisms and free radicals. In this regard, new functionalized pyrazoles have been synthesized using a simple and accessible approach. The synthesized aminobenzoylpyrazoles 3a-h and pyrazole-sulfonamides 4a-g were obtained in good yields and were evaluated in vitro for their antimicrobial and antioxidant activities. The structures of the synthesized compounds were determined using IR, NMR, and mass spectrometry. The structure of the compound 4b was further confirmed by single crystal X-ray diffraction. The results of the in vitro screening show that the synthesized pyrazoles 3 and 4 exhibit a promising antimicrobial and antioxidant activities. Among the tested compounds, pyrazoles 3a, 3f, 4e, 4f, and 4g have exhibited remarkable antimicrobial activity against some microorganisms. In addition, compounds 3a, 3c, 3e, 4a, 4d, 4f, and 4g have shown a significant antioxidant activity in comparison with the standard butylhydroxytoluene (BHT). Hence, compounds 3a, 4f, and 4g represent interesting dual acting antimicrobial and antioxidant agents. In fact, pyrazole derivatives bearing sulfonamide moiety (4a-g) have displayed an important antimicrobial activity compared to pyrazoles 3a-h, this finding could be attributed to the synergistic effect of the pyrazole and sulfonamide pharmacophores. Furthermore, Molecular docking results revealed a good interaction of the synthesized compounds with the target proteins and provided important information about their interaction modes with the target enzyme. The results of the POM bioinformatics investigations (Petra, Osiris, Molinspiration) show that the studied heterocycles present a very good non toxicity profile, an excellent bioavailability, and pharmacokinetics. Finally, an antiviral pharmacophore (O δ-, O δ-) was evaluated in the POM investigations and deserves all our attention to be tested against Covid-19 and its Omicron and Delta mutants.
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BACKGROUND: Artemisia negrei L. (A. negrei) is a medicinal and aromatic plant belonging to the family Asteraceae that is more widespread in the folded Middle Atlas Mountains, Morocco. MATERIALS AND METHODS: This study was run to investigate the phytochemical composition and antioxidant, antibacterial, and antifungal activities of Artemisia negrei L. essential oil. This oil was extracted from the fresh plant material by using the Clevenger apparatus. The phytochemical composition was characterized by GC-MS. The antioxidant activity was evaluated using different methods including DPPH, ß-carotene bleaching, and total antioxidant capacity. The antibacterial activity was tested vs. multidrug-resistant bacteria including both Gram-negative and Gram-positive using inhibition zones in agar media and minimum inhibitory concentration (MIC) bioassays. The antifungal activity was conducted on Candida albicans, Aspergillus niger, Aspergillus flavus, and Fusarium oxysporum using a solid medium assay. RESULTS: The chromatographic characterization of essential oils of A. negrei revealed the presence of 34 compounds constituting 99.91% of the total essential oil. The latter was found to have promising antioxidant activity by all bioassays used such as DPPH, ß-carotene bleaching, and total antioxidant capacity. The results obtained showed that our plant oils had potent antibacterial activity towards Gram-negative (E. coli 57, E. coli 97, K. pneumonia, and P. aeruginosa) and Gram-positive (S. aureus), so that the maximum inhibition zones and MIC values were around 18-37 mm and 3.25 to 12.5 mg/mL, respectively. The oil also showed antifungal activity towards Candida albicans, Fusarium oxysporum, and Aspergillus Niger except for flavus species. CONCLUSION: The findings obtained in the work showed that A. negrei can serve as a valuable source of natural compounds that can be used as a new weapon to fight radical damage and resistant microbes.
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BACKGROUND: Withania frutescens. L (W. frutescens) is a perennial woody medicinal plant belonging to family Solanaceae largely used by the indigenous population to Morocco for the treatment of disease. OBJECTIVE: The purpose of this study was to investigate the chemical composition, acute, and subacute toxicity of W. frutescens extract in mice. MATERIALS AND METHODS: The phytochemical composition of W. frutescens extract was determined using a gas chromatograph (GC/MS). Acute toxicity study was carried out in mice through oral administration of single doses 500 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was performed with oral administration of repeated doses 500 and 2000 mg/kg/day for 28 days. Biochemical parameters (alanine aminotransferase, aspartate aminotransferase, urea, and creatinine), as well as histopathological changes potentially occurred in organs, (liver, kidney, and spleen) were evaluated. RESULTS: The results of chromatographic analysis showed the richness of W. frutescens extract in interesting phytochemical compounds majorly constituted of bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-(C10H16). Regarding acute toxicity study, the results showed no clinical symptoms occurred in treated mice compared to the control group and no histological changes detected in analyzed organs of treated mice with dose put to 2000 mg/kg nor adverse effect on biochemical parameters. CONCLUSION: The outcome of this work showed no toxic effect of W. frutescens in mice up to dose 2000 mg/kg bodyweight. Therefore, this study could scientifically validate further traditional use with safety in the range of tested doses.