Design, synthesis and biological evaluation of novel 5-((substituted quinolin-3-yl/1-naphthyl) methylene)-3-substituted imidazolidin-2,4-dione as HIV-1 fusion inhibitors

Ibrahim, Tarek S.; Bokhtia, Riham M.; Al‐Mahmoudy, Amany M. M.; Taher, Ehab S.; AlAwadh, Mohammed A.; Elagawany, Mohamed; Abdel‐Aal, Eatedal H.; Panda, Siva S.; Gouda, Ahmed M.; Asfour, Hany Z.; Alhakamy, Nabil A.; Youssif, Bahaa G.M.

doi:10.1016/j.bioorg.2020.103782

Cited by 32 publications

(26 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All the chemicals were purchased from Sigma-Aldrich (Cairo, Egypt) or Lancaster Synthesis Corporation (London, UK). Intermediates 12 – 15a – j [ 38 , 39 , 40 ] and 17 [ 41 , 42 , 43 ], 18 [ 44 , 45 ] were prepared as previously reported.…”

Section: Methodsmentioning

confidence: 99%

Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

et al. 2020

Self Cite

View full text Add to dashboard Cite

A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound, 19h, demonstrated superior IC50 values ranging from 0.02 to 0.04 µM against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting 19h’s selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, 19h caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that 19h holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin.

show abstract

Section: Methodsmentioning

confidence: 99%

Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…All chemicals were purchased from Sigma-Aldrich or Lancaster Synthesis Corporation (UK). Intermediates 6-8a-i were prepared according to reported procedure 47,48 .…”

Section: Chemistrymentioning

confidence: 99%

“…The synthesis was initiated with acetylation of the starting aniline derivatives 5a-h using acetic anhydride and glacial acetic acid at 0 C. The produced amides 6a-h were subjected to Vilsmeier-Haack reaction to give the corresponding quinoline-3aldehyde derivatives 7a-h. Addition of methoxy substituent to 7a-h to give 8a-h was achieved through the use of sodium methoxide at 40 C in methanol 47,48 . The synthesis of the second core 3,4,5-trimethoxyphenyl moiety 11 started with acylation of the acid 9 under highly acidic condition using SOCl 2 to give acyl benzotriazole 10 (Scheme 2) 57,58 .…”

Section: Design and Chemistrymentioning

confidence: 99%

Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect

Ibrahim

Hawwas

Malebari

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC 50 ranging from 0.010 to 0.042 mM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G 2 /M phase arrest. Besides, 12c induces apoptosis via a mitochondrial-dependant apoptosis pathway and caused reactive oxygen stress generation in MCF-7 cells. These results provide guidance for further rational development of potent tubulin polymerisation inhibitors for the treatment of cancer. HIGHLIGHTS A novel series of quinoline derivatives of combretastatin A-4 have been designed and synthesised. Compound 12c showed significant antiproliferative activities against different cancer cell lines. Compound 12c effectively inhibited tubulin polymerisation and competed with [ 3 H] colchicine in binding to tubulin. Compound 12c arrested the cell cycle at G 2 /M phase, effectively inducing apoptosis and inhibition of cell migration.

show abstract

“…24,25 In the present study, CS was extracted and used to prepare three new SBs of CS by reacting CS with 2-chloroquinoline-3carbaldehyde, quinazoline-6-carbaldehyde, and oxazole-4-carbaldehyde. The structures of the prepared CSSBs were confirmed using 1H NMR, 13 C NMR, and FT-IR techniques.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, this study attempts to develop a synthesis method for three new CSSB derivatives CS-P1, CS-P2, and CS-P3 through coupling CS with 2-chloroquinoline-3carbaldehyde, quinazoline-6-carbaldehyde, and oxazole-4-carbaldehyde, respectively. The structures of the prepared derivatives were verified via FT-IR and 1 H and 13 C NMR spectroscopy. The antimicrobial potential of CS and the new derivatives was tested against four kinds of bacteria, E. coli, K. pneumonia, S. aureus, and S. mutans, in addition to two kinds of fungi, C. albicans and A. fumigates.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Three New Chitosan Schiff Base Derivatives

2020

View full text Add to dashboard Cite

Recently, chemical modifications of chitosan (CS) have attracted the attention of scientific researchers due to its wide range of applications. In this research, chitin (CH) was extracted from the scales of Cyprinus carpio fish and converted to CS by three chemical steps: (i) demineralization, (ii) deprotonation, and (iii) deacetylation. The degree (measured as a percentage) of deacetylation (DD %) was calculated utilizing the acid–base titration method. The structure of CS was characterized by Fourier transform infrared (FT-IR) spectroscopy and thermogravimetric analysis (TGA). Three new CS Schiff bases (CSSBs) (CS-P1, CS-P2, and CS-P3) were synthesized via coupling of CS with 2-chloroquinoline-3-carbaldehyde, quinazoline-6-carbaldehyde, and oxazole-4-carbaldehyde, respectively. The newly prepared derivatives were verified, structurally, by nuclear magnetic resonance (1H and 13C NMR) and FT-IR spectroscopy. Antimicrobial activity was evaluated for the prepared compounds against both “Gram-negative” and “Gram-positive” bacteria, namely, Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Streptococcus mutans, in addition to two kinds of fungi, Candida albicans and Aspergillus fumigates. Cytotoxicity of the synthesized CSSBs was evaluated via a MTT screening test. The results indicated a critical activity increase of the synthesized compound rather than CS generally tested bacteria and fungi and the absence of cytotoxic activity. These findings suggested that these new CSSBs are novel biomaterial candidates with enhanced antibacterial and nontoxic characteristics for applications in areas of both biology and medicine.

show abstract

Design, synthesis and biological evaluation of novel 5-((substituted quinolin-3-yl/1-naphthyl) methylene)-3-substituted imidazolidin-2,4-dione as HIV-1 fusion inhibitors

Cited by 32 publications

References 29 publications

Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect

Synthesis and Biological Evaluation of Three New Chitosan Schiff Base Derivatives

Contact Info

Product

Resources

About