Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors

Abdelbaset, Mahmoud S.; Abuo‐Rahma, Gamal El‐Din A.; Abdelrahman, Mostafa H.; Ramadan, Mohamed; Youssif, Bahaa G.M.; Bukhari, Syed Nasir Abbas; Mohamed, Mamdouh F. A.; Abdel‐Aziz, Mohamed

doi:10.1016/j.bioorg.2018.06.003

Cited by 53 publications

(9 citation statements)

References 34 publications

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“…Using doxorubicin as a control, the most active caspase activators 8e and 8g were further investigated for their impact on Bax and Bcl-2 levels in the MCF-7 breast cancer cell line [31,32]. Table 5 shows that 8e and 8g elicited a significant increase in Bax levels as compared to doxorubicin.…”

Section: Bax and Bcl-2 Levels Assaymentioning

confidence: 99%

Design and Synthesis of (2-oxo-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents

et al. 2021

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A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)bis(4-hydroxyquinolin-2(1H)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products are interesting precursors for their anti-proliferative activity. Compound 8g was the most active one, achieving IC50 = 1.2 ± 0.2 µM and 1.4 ± 0.2 µM against MCF-7 and Panc-1 cell lines, respectively. Moreover, cell cycle analysis of cells MCF-7 treated with 8g showed cell cycle arrest at the G2/M phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant pro-apoptotic activity is indicated by annexin V-FITC staining.

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Section: Bax and Bcl-2 Levels Assaymentioning

confidence: 99%

Design and Synthesis of (2-oxo-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents

et al. 2021

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“…In literature data, it is reported that quinoline-1,3,4-oxadiazole hybrid V (Fig. 2) showed higher antibacterial activity against Staphylococcus aureus as a Gram-positive strain tested with a MIC value equal to 10 ng/mL, which is threefold lower than that of ciprofloxacin (30 ng/mL), and equal to 25 ng/mL against Escherichia coli Gram-negative bacteria in emulation to ciprofloxacin with MIC value equal to 60 ng/mL [41]. Upon depending on the hybridization strategy in design of this research work, the aim is to synthesize a new ciprofloxacin-linked quinoline hybrids via a quinoline-4-carbonyl linker (8a-c) or quinolin-4-yl-1,3,4oxadiazole linker (6a-c); to study the impact of binding these groups to the C-7-piperazine moiety on antimicrobial and anticancer activities (Fig.…”

Section: Introductionmentioning

confidence: 90%

Design, synthesis, and biological investigation of quinoline/ciprofloxacin hybrids as antimicrobial and anti-proliferative agents

et al. 2022

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Ciprofloxacin-Piperazine C-7 linked quinoline derivatives 6a–c and 8a–c were synthesized and investigated for their antibacterial, antifungal, and anti-proliferative activities. Ciprofloxacin-quinoline-4-yl-1,3,4 oxadiazoles 6a and 6b showed promising anticancer activity against SR- leukemia and UO-31 renal cancer cell lines. The hybrids 8a–c and compound 6b exhibited noticeable antifungal activities against C.Albicans; 8a experienced the most potent antifungal activity compared to Itraconazole with MICs of 21.88 µg/mL and 11.22 µg/mL; respectively. Most of derivatives displayed better antibacterial activity than the parent ciprofloxacin against all the tested strains. Compound 6b was the most potent against the highly resistant Gram-negative K.pneumoniae with MIC 16.96 of µg/mL relative to the parent ciprofloxacin (MIC = 29.51 µg/mL). Docking studies of the tested hydrides in the active site of Topo IV enzyme of K.pneumoniae (5EIX) and S.aureus gyrase (2XCT) indicate that they had stronger binding affinity in both enzymes than ciprofloxacin but have different binding interactions. The hybrid 6b could be considered a promising lead compound for finding new dual antibacterial/anticancer agents. Moreover, Compound 8a could be a lead for discovering new dual antibacterial/antifungal agents. Graphical abstract

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“…Quinoline-based compounds play a vital role in the development of anti-cancer drugs. They have been very successful with different mechanisms of action, such as growth inhibition by cell cycle arrest, apoptosis, angiogenesis inhibition, cell migration disruption, and modulation [ 64 ]. The quinoline hybrids with a tubulin polymerization-disrupting mechanism are described in this review.…”

Section: Quinoline Hybridsmentioning

confidence: 99%

A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization

Ebenezer

Shapi

Tuszyński

2022

IJMS

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Microtubules are cylindrical protein polymers formed from αβ-tubulin heterodimers in the cytoplasm of eukaryotic cells. Microtubule disturbance may cause cell cycle arrest in the G2/M phase, and anomalous mitotic spindles will form. Microtubules are an important target for cancer drug action because of their critical role in mitosis. Several microtubule-targeting agents with vast therapeutic advantages have been developed, but they often lead to multidrug resistance and adverse side effects. Thus, single-target therapy has drawbacks in the effective control of tubulin polymerization. Molecular hybridization, based on the amalgamation of two or more pharmacophores of bioactive conjugates to engender a single molecular structure with enhanced pharmacokinetics and biological activity, compared to their parent molecules, has recently become a promising approach in drug development. The practical application of combined active scaffolds targeting tubulin polymerization inhibitors has been corroborated in the past few years. Meanwhile, different designs and syntheses of novel anti-tubulin hybrids have been broadly studied, illustrated, and detailed in the literature. This review describes various molecular hybrids with their reported structural–activity relationships (SARs) where it is possible in an effort to generate efficacious tubulin polymerization inhibitors. The aim is to create a platform on which new active scaffolds can be modeled for improved tubulin polymerization inhibitory potency and hence, the development of new therapeutic agents against cancer.

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Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors

Cited by 53 publications

References 34 publications

Design and Synthesis of (2-oxo-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents

Design and Synthesis of (2-oxo-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents

Design, synthesis, and biological investigation of quinoline/ciprofloxacin hybrids as antimicrobial and anti-proliferative agents

A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization

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