One-pot strategy for thiazole tethered 7-ethoxy quinoline hybrids: Synthesis and potential antimicrobial agents as dihydrofolate reductase (DHFR) inhibitors with molecular docking study
TL;DR: Molecular docking study against DHFR enzyme (1DLS) was carried out, and the active derivatives bind to some the nearly the same amino acid residues as MTX that support the hypothesis that quinoline antibiotic class can be solved by discovering new targets and inhibitors.
About: This article is published in Journal of Molecular Structure.The article was published on 2021-10-15. It has received 29 citations till now. The article focuses on the topics: Dihydrofolate reductase & Quinoline.
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TL;DR: In this article, a series of new bis-thiazolyl-pyrazole derivatives 3, 4a-c, 5a, b, and 6a -c was synthesized by reacting bis hydrazonoyl bromide with several active methylene reagents in a one-pot reaction.
34 citations
TL;DR: In this paper, a series of new magenta azomethine reactive disperse dyes were synthesized and applied into polyester/cotton blend fabrics, and various spectroscopic and analytical techniques characterized all the synthesized dyes.
33 citations
TL;DR: In this paper , a series of new thiazolo-indolin-2-one derivatives were synthesized based on acid and base catalyzed condensation or reaction of thiosemicarbazone 8 with different electrophilic reagents.
31 citations
TL;DR: This study aims to design a simple and efficient cyclo-condensation reaction of 6-aminouracil derivatives 2a–e and isatin derivatives 1a–c to synthesize spiro-oxindoles 3a–d, 4 a–e, and 5a-e to synthesise spiro’s most active hybrids.
Abstract: The first outbreak in Wuhan, China, in December 2019 was reported about severe acute coronaviral syndrome 2 (SARS-CoV-2). The global coronavirus disease 2019 (COVID-19) pandemic in 2020 resulted in an extremely high potential for dissemination. No drugs are validated in large-scale studies for significant effectiveness in the clinical treatment of COVID-19 patients, despite the worsening trends of COVID-19. This study aims to design a simple and efficient cyclo-condensation reaction of 6-aminouracil derivatives 2a–e and isatin derivatives 1a–c to synthesize spiro-oxindoles 3a–d, 4a–e, and 5a–e. All compounds were tested in vitro against the SARS-CoV-2. Four spiro[indoline-3,5′-pyrido[2,3-d:6,5-d’]dipyrimidine derivatives 3a, 4b, 4d, and 4e showed high activities against the SARS-CoV-2 in plaque reduction assay and were subjected to further RNA-dependent-RNA-polymerase (RdRp) and spike glycoprotein inhibition assay investigations. The four compounds exhibited potent inhibitory activity ranging from 40.23 ± 0.09 to 44.90 ± 0.08 nM and 40.27 ± 0.17 to 44.83 ± 0.16 nM, respectively, when compared with chloroquine as a reference standard, which showed 45 ± 0.02 and 45 ± 0.06 nM against RdRp and spike glycoprotein, respectively. The computational study involving the docking studies of the binding mode inside two proteins ((RdRp) (PDB: 6m71), and (SGp) (PDB: 6VXX)) and geometrical optimization used to generate some molecular parameters were performed for the most active hybrids.
29 citations
TL;DR: A series of 6-(morpholinosulfonyl)quinoxalin-2(1H)-one based hydrazone, hydrazine, and pyrazole moieties were designed, synthesized, and evaluated for their in vitro antimicrobial activity.
29 citations
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01 Jan 2000
16,612 citations
Journal Article•
TL;DR: Decades after the first patients were treated with antibiotics, bacterial infections have again become a threat because of the rapid emergence of resistant bacteria-a crisis attributed to abuse of these medications and a lack of new drug development.
Abstract: Decades after the first patients were treated with antibiotics, bacterial infections have again become a threat because of the rapid emergence of resistant bacteria-a crisis attributed to abuse of these medications and a lack of new drug development.
3,147 citations
TL;DR: This review will focus on the emergence of antimicrobial resistance in S. aureus, the leading overall cause of nosocomial infections and, as more patients are treated outside the hospital setting, is an increasing concern in the community.
Abstract: In the early 1970s, physicians were finally forced to abandon their belief that, given the vast array of effective antimicrobial agents, virtually all bacterial infections were treatable. Their optimism was shaken by the emergence of resistance to multiple antibiotics among such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. The evolution of increasingly antimicrobial-resistant bacterial species stems from a multitude of factors that includes the widespread and sometimes inappropriate use of antimicrobials, the extensive use of these agents as growth enhancers in animal feed, and, with the increase in regional and international travel, the relative ease with which antimicrobial-resistant bacteria cross geographic barriers (1–3).
The irony of this trend toward progressively more resistant bacteria is that it coincides with a period of dramatically increased understanding of the molecular mechanisms of antimicrobial resistance. Unfortunately, while this insight has resulted in the identification of novel drug targets, it has not yet resulted in effective new chemotherapeutic agents. This paradox stands in sharp contrast to the dramatic progress made in antiviral (notably antiretroviral) therapy in the past ten years, where a number of newly discovered molecular targets have resulted in clinically effective therapeutic agents.
Nowhere has this issue been of greater concern than with the Gram-positive bacteria pneumococci, enterococci, and staphylococci. Multidrug resistance is now the norm among these pathogens. S. aureus is perhaps the pathogen of greatest concern because of its intrinsic virulence, its ability to cause a diverse array of life-threatening infections, and its capacity to adapt to different environmental conditions (4, 5). The mortality of S. aureus bacteremia remains approximately 20–40% despite the availability of effective antimicrobials (6). S. aureus is now the leading overall cause of nosocomial infections and, as more patients are treated outside the hospital setting, is an increasing concern in the community (7, 8).
S. aureus isolates from intensive care units across the country and from blood culture isolates worldwide are increasingly resistant to a greater number of antimicrobial agents (4, 8). Inevitably this has left fewer effective bactericidal antibiotics to treat these often life-threatening infections (Figure (Figure1).1). As rapidly as new antibiotics are introduced, staphylococci have developed efficient mechanisms to neutralize them (Table (Table11).
Figure 1
S. aureus infections in intensive care units in the National Nosocomial Infections Surveillance System. Data include the total number of infections from 1987 to 1997. Isolates were tested for sensitivity to the following antimicrobial agents: gentamicin, ...
Table 1
Mechanisms of S. aureus resistance to antimicrobialsA
Recent reports of S. aureus isolates with intermediate or complete resistance to vancomycin portend a chemotherapeutic era in which effective bactericidal antibiotics against this organism may no longer be readily available (9, 10). This review will focus on the emergence of antimicrobial resistance in S. aureus. It will review the historical evolution of resistant strains, their spread, the molecular mechanisms of resistance for selected antibiotics, and progress toward the development of alternative drug targets or novel approaches for therapeutic or prophylactic intervention.
1,382 citations
TL;DR: Enterococci associated with cultures obtained from burn patients have been on the increase, worldwide, over the past decade and are now among the four most common nosocomial pathogens in the US and have been called the ‘nosocomial infections of the 1990s’.
1,165 citations
TL;DR: The more significant bioactivities of a variety of semicarbazones (anti-protozoa, anticonvulsant) and thiosemicarbazone and their metal complexes are reviewed together with proposed mechanisms of action and structure-activity relationships.
Abstract: The more significant bioactivities of a variety of semicarbazones (anti-protozoa, anticonvulsant) and thiosemicarbazones (antibacterial, antifungal, antitumoral, antiviral) and their metal complexes are reviewed together with proposed mechanisms of action and structure-activity relationships. Clinical or potential pharmacological applications of these versatile compounds are discussed.
669 citations