One-pot synthesis and molecular docking of some new spiropyranindol-2-one derivatives as immunomodulatory agents and in vitro antimicrobial potential with DNA gyrase inhibitor
TL;DR: The most potent compounds showed an increase in the intracellular killing activity of neutrophils which confirmed the immunostimulatory power, and compounds 7f showed the much better than norfloxacin with higher potency results.
About: This article is published in European Journal of Medicinal Chemistry.The article was published on 2020-02-15. It has received 59 citations till now. The article focuses on the topics: DNA gyrase & Norfloxacin.
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TL;DR: In this paper, the authors provide a description of the general chemistry based on existing corresponding structureactivity relationships (SARs) and compile all recent developmentary studies on oxindole-derived compounds as a successful pharmaceutical agent.
75 citations
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TL;DR: The most potent compounds 2, 7, 9, 10, 12 and 13c were exhibited bactericidal activity, in addition to fungistatic activity by dead live assay, and showed a significant result against all multi-drug resistance (MDRB) used especially compound 13c that displayed the best results with MICs of MDRB.
52 citations
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TL;DR: Immunomodulatory activities showed that the promising Schiff bases increase the immunomodulator effect of defense cell and the Schiff base 8a is the highest one by (Intra. killing activity = 136.5 ± 0.3%) having a pyrazole moiety as well as amide function (O=C-NH2) and piperidinyl core.
Abstract: A series of Bis-pyrazole Schiff bases (6a-d and 7a-d) and mono-pyrazole Schiff bases (8a-d and 9a-d) were designed and synthesized through the reaction of 5-aminopyrazoles 1a-d with aldehydes 2-5 using mild reaction condition with a good yield percentage. The chemical structure of newly formed Schiff bases tethered pyrazole core was confirmed based on spectral and experimental data. All the newly formed pyrazole Schiff bases were evaluated against eight pathogens (Gram-positive, Gram-negative, and fungi). The result exhibited that, most of them have good and broad activities. Among those, only six Schiff bases (6b, 7b, 7c, 8a, 8d, and 9b) displayed MIC values (0.97-62.5 µg/mL) compared to Tetracycline (15.62-62.5 µg/mL) and Amphotericin B (15.62-31.25 µg/mL), MBC values (1.94-87.5 µg/mL) and selectivity to tumor cell than normal cells. Immunomodulatory activities showed that the promising Schiff bases increase the immunomodulator effect of defense cell and the Schiff base 8a is the highest one by (Intra. killing activity = 136.5 ± 0.3%) having a pyrazole moiety as well as amide function (O=C-NH2) and piperidinyl core. Furthermore, the most potent one exhibited broad activity depending on both MIC and MBC values. Moreover, to study the mechanism of these pyrazole Schiff bases, two active Schiff bases 8a and 9b from six derivatives were introduced to study the enzyme assay as dihydrofolate reductase (DHFR) on E. coli organism and DNA gyrase with two different organisms, S. aureus and B. subtilis, to determine the inhibitory activities with lower values in the case of DNA gyrase (8a and 9b) or nearly as DHFR compound 9b, while pyrazole 8a showed excellent inhibitory against all enzyme assay. The molecular docking study against dihydrofolate reductase and DNA gyrase were performed to study the binding between active site in the pocket with the two Schiff bases (8a and 9b) that exhibited good binding affinity with different bond types as H-bonding, aren-aren, and arene-cation interaction as well as study the physicochemical and pharmacokinetic properties of the two active Schiff bases 8a and 9b.
49 citations
Cites background or methods from "One-pot synthesis and molecular doc..."
...aureus DNA gyrase enzyme (PDB: 2XCT) and Ciprofloxacin was found co-crystallized inside the pocket [57,60]....
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...87 Kcal/mol), respectively (see Table 9) [57,60]....
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...The immunomodulatory activity of the potent Schiff bases (6b, 7b, 7c, 8a, 8d, and 9b) was evaluated according to previous work [57,66]....
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...The docking process methodology of new compounds was performed according to previous work [57,58,68]....
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...MBC is usually presented as MBC50, which means the drug concentration kills 50% of the initial bacterial population [57]....
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TL;DR: A series of Schiff bases 3, 5, 7 and hydrazones 9 were achieved via reaction of 5-(morpholinosulfonyl)indol-2,3-dione with appropriate amines and/or hydrazide derivatives and enabled a better understanding of their structural features.
48 citations
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TL;DR: A new series of quinoxaline derivatives synthesized and pharmacologically evaluated against (HepG-2, HCT-116, and MCF-7) cell lines and revealed that it increases apoptotic cells and induced cell cycle arrest at pre-G1 and G2/M phases.
39 citations
References
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TL;DR: The biotech industry is establishing itself as the discovery arm of the pharmaceutical industry, and in bridging the gap between academia and large pharmaceutical companies, the biotech firms have been effective instruments of technology transfer.
Abstract: Driven by chemistry but increasingly guided by pharmacology and the clinical sciences, drug research has contributed more to the progress of medicine during the past century than any other scientific factor. The advent of molecular biology and, in particular, of genomic sciences is having a deep impact on drug discovery. Recombinant proteins and monoclonal antibodies have greatly enriched our therapeutic armamentarium. Genome sciences, combined with bioinformatic tools, allow us to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future medicines, thereby increasing the number of treatment options. The dramatic increase in the complexity of drug research is enforcing changes in the institutional basis of this interdisciplinary endeavor. The biotech industry is establishing itself as the discovery arm of the pharmaceutical industry. In bridging the gap between academia and large pharmaceutical companies, the biotech firms have been effective instruments of technology transfer.
2,551 citations
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TL;DR: The method, termed topological PSA (TPSA), provides results which are practically identical with the 3D PSA, while the computation speed is 2-3 orders of magnitude faster and may be used for fast bioavailability screening of virtual libraries having millions of molecules.
Abstract: Molecular polar surface area (PSA), i.e., surface belonging to polar atoms, is a descriptor that was shown to correlate well with passive molecular transport through membranes and, therefore, allows prediction of transport properties of drugs. The calculation of PSA, however, is rather time-consuming because of the necessity to generate a reasonable 3D molecular geometry and the calculation of the surface itself. A new approach for the calculation of the PSA is presented here, based on the summation of tabulated surface contributions of polar fragments. The method, termed topological PSA (TPSA), provides results which are practically identical with the 3D PSA (the correlation coefficient between 3D PSA and fragment-based TPSA for 34 810 molecules from the World Drug Index is 0.99), while the computation speed is 2-3 orders of magnitude faster. The new methodology may, therefore, be used for fast bioavailability screening of virtual libraries having millions of molecules. This article describes the new methodology and shows the results of validation studies based on sets of published absorption data, including intestinal absorption, Caco-2 monolayer penetration, and blood-brain barrier penetration.
2,400 citations
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TL;DR: Chronic granulomatous disease is an X-linked defect in the killing of certain bacteria by peripheral blood granulocytes and may be detected with the nitroblue tetrazolium (NBT) test.
Abstract: Chronic granulomatous disease is an X-linked defect in the killing of certain bacteria by peripheral blood granulocytes and may be detected with the nitroblue tetrazolium (NBT) test. The r...
860 citations
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TL;DR: The efficiency of separation of MN and PMN leucocytes by the Hypaque-Ficoll method was dependent on both the Ficoll concentration and the density of the medium.
552 citations
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TL;DR: It was shown that the difficultly accessible isopropylidene side chain of spirotryprostatin A is not necessary for biological activity and three analogues lacking the diketopiperazine system were shown to be quite active as cell cycle inhibitors.
Abstract: The total synthesis of the title compound has been accomplished. A key step involves the oxidative rearrangement of the β-carboline derivative to an oxindole via the action of N-bromosuccinimide. From this point, a diketopiperazine was introduced. A thiophenyl group served as a precursor of the isopropylidene function. Implementation of the same sort of chemistry starting with a methoxytryptophan derivative led to the parent structures. Furthermore, it was shown that the difficultly accessible isopropylidene side chain of spirotryprostatin A is not necessary for biological activity. Moreover, three analogues lacking the diketopiperazine system were shown to be quite active as cell cycle inhibitors.
387 citations