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      Design, synthesis, characterization, in vitro screening, molecular docking, 3D-QSAR, and ADME-Tox investigations of novel pyrazole derivatives as antimicrobial agents

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          Abstract

          Novel pyrazoles were synthesized and evaluated for their antimicrobial activity. Molecular docking, 3D-QSAR, drug-likeness property and ADME-Tox studies were performed.

          Abstract

          In this work, we report the synthesis of some new pyrazole derivatives via an efficient and practical procedure. The structures of the obtained compounds were established using different spectroscopic techniques such as NMR and FT-IR spectroscopy as well as high resolution mass spectrometry (HRMS). The synthesized compounds were screened for their antimicrobial activity against the following pathogenic microorganisms: Listeria innocua (CECT 4030), Staphylococcus aureus (CECT 976), Escherichia coli (K12), and Candida albicans (ATCC 10231). The results of the in vitro tests reveal that compounds 5c, 9b, and 9c exhibit important antimicrobial activity against some tested microbe strains, and show excellent bactericidal and fungicidal activities. A molecular docking study was performed on the most active compounds against E. coli and C. albicans receptors, in order to determine the modes of hydrogen bonding, and electrostatic and hydrophobic interactions that occur between the selected ligands and the target proteins. Furthermore, the 3D-QSAR study based on CoMFA and CoMSIA analyses ascertained a good correlation between the antibacterial activity of the pyrazole derivatives and their structural parameters. The structural features identified in these analyses were successfully used to design new pyrazole derivatives that show better in silico antimicrobial activity than the synthesized ones. In addition, most of the synthesized and the newly designed compounds show good drug-like properties. The ADME-Tox profiles indicate a good oral bioavailability. The newly designed compounds were subjected to molecular docking, which showed that they could form stable complexes with the E. coli receptor. Therefore, the obtained results in this study might provide important information for designing and synthesizing new pyrazoles with enhanced antimicrobial activity.

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          Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study.

          Nosocomial bloodstream infections (BSIs) are important causes of morbidity and mortality in the United States. Data from a nationwide, concurrent surveillance study (Surveillance and Control of Pathogens of Epidemiological Importance [SCOPE]) were used to examine the secular trends in the epidemiology and microbiology of nosocomial BSIs. Our study detected 24,179 cases of nosocomial BSI in 49 US hospitals over a 7-year period from March 1995 through September 2002 (60 cases per 10,000 hospital admissions). Eighty-seven percent of BSIs were monomicrobial. Gram-positive organisms caused 65% of these BSIs, gram-negative organisms caused 25%, and fungi caused 9.5%. The crude mortality rate was 27%. The most-common organisms causing BSIs were coagulase-negative staphylococci (CoNS) (31% of isolates), Staphylococcus aureus (20%), enterococci (9%), and Candida species (9%). The mean interval between admission and infection was 13 days for infection with Escherichia coli, 16 days for S. aureus, 22 days for Candida species and Klebsiella species, 23 days for enterococci, and 26 days for Acinetobacter species. CoNS, Pseudomonas species, Enterobacter species, Serratia species, and Acinetobacter species were more likely to cause infections in patients in intensive care units (P<.001). In neutropenic patients, infections with Candida species, enterococci, and viridans group streptococci were significantly more common. The proportion of S. aureus isolates with methicillin resistance increased from 22% in 1995 to 57% in 2001 (P<.001, trend analysis). Vancomycin resistance was seen in 2% of Enterococcus faecalis isolates and in 60% of Enterococcus faecium isolates. In this study, one of the largest multicenter studies performed to date, we found that the proportion of nosocomial BSIs due to antibiotic-resistant organisms is increasing in US hospitals.
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            Infectious Disease Threats in the Twenty-First Century: Strengthening the Global Response

            The world has developed an elaborate global health system as a bulwark against known and unknown infectious disease threats. The system consists of various formal and informal networks of organizations that serve different stakeholders; have varying goals, modalities, resources, and accountability; operate at different regional levels (i.e., local, national, regional, or global); and cut across the public, private-for-profit, and private-not-for-profit sectors. The evolving global health system has done much to protect and promote human health. However, the world continues to be confronted by longstanding, emerging, and reemerging infectious disease threats. These threats differ widely in terms of severity and probability. They also have varying consequences for morbidity and mortality, as well as for a complex set of social and economic outcomes. To various degrees, they are also amenable to alternative responses, ranging from clean water provision to regulation to biomedical countermeasures. Whether the global health system as currently constituted can provide effective protection against a dynamic array of infectious disease threats has been called into question by recent outbreaks of Ebola, Zika, dengue, Middle East respiratory syndrome, severe acute respiratory syndrome, and influenza and by the looming threat of rising antimicrobial resistance. The concern is magnified by rapid population growth in areas with weak health systems, urbanization, globalization, climate change, civil conflict, and the changing nature of pathogen transmission between human and animal populations. There is also potential for human-originated outbreaks emanating from laboratory accidents or intentional biological attacks. This paper discusses these issues, along with the need for a (possibly self-standing) multi-disciplinary Global Technical Council on Infectious Disease Threats to address emerging global challenges with regard to infectious disease and associated social and economic risks. This Council would strengthen the global health system by improving collaboration and coordination across organizations (e.g., the WHO, Gavi, CEPI, national centers for disease control, pharmaceutical manufacturers, etc.); filling in knowledge gaps with respect to (for example) infectious disease surveillance, research and development needs, financing models, supply chain logistics, and the social and economic impacts of potential threats; and making high-level, evidence-based recommendations for managing global risks associated with infectious disease.
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              Author and article information

              Contributors
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              Journal
              NJCHE5
              New Journal of Chemistry
              New J. Chem.
              Royal Society of Chemistry (RSC)
              1144-0546
              1369-9261
              February 07 2022
              2022
              : 46
              : 6
              : 2747-2760
              Affiliations
              [1 ]Engineering Laboratory of Organometallic and Molecular Materials and Environment (LIMOME), Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796 (Atlas), 30000 Fez, Morocco
              [2 ]Université Sidi Mohamed Ben Abdellah, Cité de l’innovation, Fès, Morocco
              [3 ]Laboratory of Biotechnology, Environment, Agri-Food, and Health (LBEAS), Faculty of Sciences, University Sidi Mohamed Ben Abdellah (USMBA), 30050 Fez, Morocco
              [4 ]Laboratory of Engineering, Systems and Applications, National School of Applied Sciences, Sidi Mohamed Ben Abdellah-Fez University, Fez, Morocco
              [5 ]Laboratory of Bioorganic Chemistry, Department of Chemistry, Faculty of Sciences, Chouaïb Doukkali University, P.O. Box 24, 24000 El Jadida, Morocco
              [6 ]Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, B.P. 7955, Casablanca, Morocco
              Article
              10.1039/D1NJ05621B
              7f84bd62-466b-43cf-a6cf-1acb65868045
              © 2022

              http://rsc.li/journals-terms-of-use

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