In vitro cytotoxic activity of thiazole-indenoquinoxaline hybrids as apoptotic agents, design, synthesis, physicochemical and pharmacokinetic studies

Fayed, Eman A.; Ammar, Yousry A.; Ragab, Ahmed; Gohar, Nirvana A.; Mehany, Ahmed B. M.; Farrag, Ayman A.

doi:10.1016/j.bioorg.2020.103951

Cited by 46 publications

(22 citation statements)

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“…Prediction of Some Physicochemical, Pharmacokinetic, and Toxicity Properties Physicochemical properties are a widely recognized tool for designing bioavailable drugs and many efforts to assess drug "developability" depend on the calculated and measured physicochemical parameters [74]. As described in Table 10, some of the molecular properties for the most promising derivatives, 2a, 2b, 2d, 3a, 8, and 11, were calculated using the Swiss ADME tool (http://swissadme.ch/index.php (accessed on 21 October 2020)), as described in previously reported methods [59], to evaluate the drug-likeness properties. All the most active derivatives were found to have a number of rotatable bonds, a hydrogen bond acceptor and donor, as well as molecular weight and lipophilicity properties (MLogP), with the criteria limitation of Lipinski's rule without any violation.…”

Section: 3mentioning

confidence: 99%

“…Activation of T lymphocytes, natural killer, and macrophage cells mainly produce the cytokines that have immunomodulatory potential and plays a vital role in the immune response process by assisting the expulsion of abnormal cells [50]. In view of the above observations and in continuation of our program on the medicinal chemistry that demonstrated biological activity [51][52][53][54][55][56][57][58][59][60]. We report herein the synthesis of the versatile hitherto unknown 2-pyridone and chromeno- [3,4-c] pyridine derivatives containing the sulfaguanidine moiety in a single molecular framework; the rational study design is presented in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

“…Antibiotics 2021, 10, x FOR PEER REVIEW 3 of 31 the expulsion of abnormal cells [50]. In view of the above observations and in continuation of our program on the medicinal chemistry that demonstrated biological activity [51][52][53][54][55][56][57][58][59][60].…”

Section: Introductionmentioning

confidence: 99%

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Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors

et al. 2021

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Herein, a series of novel hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide 2a–d, pyridine-2-one 3–10, and 2-imino-2H-chromene-3-carboxamide 11, 12 derivatives, were synthesized, and their structure confirmed by spectral data and elemental analysis. All the synthesized compounds showed moderate to good antimicrobial activity against eight pathogens. The most promising six derivatives, 2a, 2b, 2d, 3a, 8, and 11, revealed to be best in inhibiting bacterial and fungal growth, thus showing bactericidal and fungicidal activity. These derivatives exhibited moderate to potent inhibition against DNA gyrase and DHFR enzymes, with three derivatives 2d, 3a, and 2a demonstrating inhibition of DNA gyrase, with IC50 values of 18.17–23.87 µM, and of DHFR, with IC50 values of 4.33–5.54 µM; their potency is near to that of the positive controls. Further, the six derivatives exhibited immunomodulatory potential and three derivatives, 2d, 8, and 11, were selected for further study and displayed an increase in spleen and thymus weight and enhanced the activation of CD4+ and CD8+ T lymphocytes. Finally, molecular docking and some AMED studies were performed.

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Section: 3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors

et al. 2021

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“…Based on the above findings, and in continuation to our work on the synthesis of new compounds with biological activities [28][29][30][31][32][33][34], we have synthesized a new series of quinolone-3-carboxamide derivatives containing a series of biologically active moites that are expected to be strongly inhibitory for several human cell lines and PIM-1 inhibitors as a result of our commitment to search for new potential anticancer agents related to heterocyclic [35][36][37][38][39][40][41][42]. | P a g e…”

Section: Figure 1: Structures For Pim-1 Inhibitors and The Newly Designed Quinoline Hybridsmentioning

confidence: 99%

“…Fetal bovine serum was obtained from (GIBCO, UK). The different cell lines mentioned above were used to determine the inhibitory effects of the tested compounds on cell growth using the SRB assay (SulphoRhodamine-B) [37].This colorimetric assay is based on the ability of SRB to bind to protein components of cells that have been fixed in tissue culture plates by trichloroacetic acid (TCA).…”

Section: N-(4-(((2-chloroquinolin-3-yl)methylene)amino)phenyl)-2-imino-2h-chromene-3-carboxamide (10)mentioning

confidence: 99%

Carboxamide appended quinoline moieties as potential anti-proliferative agents, apoptotic inducers and Pim-1 kinase inhibitors

et al. 2021

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The targeted approach of protein kinases (PKs), as PKs are the main regulators of cell survival and proliferation, has been a promising strategy for treatments for cancer. Here we analyze the potential of quinoline-carboximide derivatives for four cell lines: MCF-7, CACO, HepG-2 and HCT-116 as anticancer agents. 3e, 4b, 11b and 13d derivatives showed good anti-proliferative activities in comparison to the reference standard Doxorubicin, against the four cell lines tested. They have been chosen for further studies. First of all, the IC50 value surveys were carried out to ensure the protection of our hits and demonstrate that the cytotoxic effect (IC50 > 113 μM) is highly selective on normal human cells (WI-38). Secondly, apoptosis was accomplished by down-regulation of Bcl-2 and up-regulation of BAX and Caspase-3 by these active compounds. Also, the Pim-1 inhibitory activity of the active hybrids was done, which indicate that compound 3e was the most active with percentage of inhibition 82.27% and IC50 equal 0.11 when compaired to SGI-1776 as a reference standered. In addition, the in silico assessment of ADME properties, all of the strongest compounds are orally bioavailable without blood brain barrier penetration.

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Design, synthesis, molecular modeling, and antimicrobial potential of novel 3‐[(1H‐pyrazol‐3‐yl)imino]indolin‐2‐one derivatives as DNA gyrase inhibitors

Ammar

Salem

Abu-Elghait

2021

Archiv der Pharmazie

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A series of 3-[(1H-pyrazol-3-yl)imino]indolin-2-one derivatives were designed using the molecular hybridization method, characterized using different spectroscopic techniques, and evaluated for their in vitro antimicrobial activity. Most of the target compounds demonstrated good to moderate antimicrobial activity compared with ciprofloxacin and fluconazole. Four compounds (8b, 9a, 9c, and 10a) showed encouraging results, with minimal inhibitory concentration (MIC) values (53.45-258.32 µM) comparable to those of norfloxacin (100.31-200.63 µM) and ciprofloxacin (48.33-96.68 µM). Noticeably, the four derivatives revealed excellent bactericidal and fungicidal activities, except for the bacteriostatic potential of compounds 8b and 9a against Escherichia coli and Staphylococcus aureus, respectively. The time-killing kinetic study against S. aureus confirmed the efficacy of these derivatives. Furthermore, two of the four promising derivatives, 9a and 10a, could prevent the formation of biofilms of S. aureus without affecting the bacterial growth at low concentrations. A combination study with seven commercial antibiotics against the multidrug-resistant bacterium P. aeruginosa showed a notable reduction in the antibiotic MIC values, represented mainly through a synergistic or additive effect. The enzymatic assay implied that the most active derivatives had inhibition potency against DNA gyrase comparable to that of ciprofloxacin. Molecular docking and density functional theory calculations were performed to explore the binding mode and study the reactivity of the promising compounds.3-(pyrazol-3-yl)imino-2-oxoindoline derivatives, antibiofilm, antimicrobial activity, DFT calculations, DNA gyrase, drug combination, molecular docking, time-killing kinetics | INTRODUCTIONIn recent years, infectious diseases caused by bacterial pathogens have become a main public health problem due to the high occurrence of drug resistance. [1] Additionally, infections caused by multidrug-resistant bacteria are a major health concern worldwide. [2] Particularly important are infections caused by the Gram-positive bacteria Staphylococcus aureus and species of the genus Enterococcus due to the increasing incidence of infections caused by these microorganisms in hospitals and communities and their ability to

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In vitro cytotoxic activity of thiazole-indenoquinoxaline hybrids as apoptotic agents, design, synthesis, physicochemical and pharmacokinetic studies

Cited by 46 publications

References 47 publications

Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors

Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors

Carboxamide appended quinoline moieties as potential anti-proliferative agents, apoptotic inducers and Pim-1 kinase inhibitors

Design, synthesis, molecular modeling, and antimicrobial potential of novel 3‐[(1H‐pyrazol‐3‐yl)imino]indolin‐2‐one derivatives as DNA gyrase inhibitors

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