New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies

Gaber, Abd El‐Aal M.; Sobhy, Mohamed; Turky, Abdallah; Eldehna, Wagdy M.; El‐Sebaey, Samiha A.; El‐Metwally, Souad A.; El‐Naggar, Abeer M.; Ibrahim, Ibrahim M.; Elkaeed, Eslam B.; Metwaly, Ahmed M.; Eissa, Ibrahim H.

doi:10.1371/journal.pone.0274081

Cited by 6 publications

(4 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The obtained effects of compounds 8b and 9b were consistent with those of known EGFR inhibitors. [29][30][31] Annexin V-FITC apoptosis assay…”

Section: Cell Cycle Analysismentioning

confidence: 99%

Novel 2‐[thio]acetamide linked quinazoline/1,2,4‐triazole/chalcone hybrids: Design, synthesis, and anticancer activity as EGFR inhibitors and apoptotic inducers

Abdelkhalek,

Kothayer,

Soltan

et al. 2024

Archiv der Pharmazie

View full text Add to dashboard Cite

Novel triazoloquinazolines carrying the 2‐[thio]acetamide entity (4 and 5a–d) and triazoloquinazoline/chalcone hybrids incorporating the 2‐[thio]acetamide linker (8a–b and 9a–f) were developed as anticancer candidates. NCI screening of the synthesized compounds at 10 μM concentration displayed growth inhibition not only up to 99.74% as observed for 9a but also a lethal effect could be achieved as stated for compounds 9c (RPMI‐8226 and HCT‐116) and 8b, 9a, and 9e on the HCT‐116 cell line. The antiproliferative activity was determined for the chalcone series on three cell lines: RPMI‐8226, HCT‐116, and MCF‐7. Compounds 8b, 9a, 9b, and 9f were the most active ones. To understand the mechanistic study, the inhibitory effect on the epidermal growth factor receptor (EGFR) kinase was evaluated. The results stated that the activity of compound 8b (IC50 = 0.07 μM) was near that of the reference drug erlotinib (IC50 = 0.052 μM) whereas compound 9b (IC50 = 0.045 μM) was found to be more potent than erlotinib. Both compounds 8b and 9b were selected for cell cycle analysis and apoptotic assays. Moreover, molecular docking results of the selected chalcone hybrids showed high binding scores and good binding affinities especially for 8b and 9b, which were consistent with the biological activity (EGFR).

show abstract

“…The obtained effects of compounds 8b and 9b were consistent with those of known EGFR inhibitors. [29][30][31] Annexin V-FITC apoptosis assay…”

Section: Cell Cycle Analysismentioning

confidence: 99%

Novel 2‐[thio]acetamide linked quinazoline/1,2,4‐triazole/chalcone hybrids: Design, synthesis, and anticancer activity as EGFR inhibitors and apoptotic inducers

Abdelkhalek,

Kothayer,

Soltan

et al. 2024

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

“…The targeted compound 25 was obtained from the treatment of 24 with POCl 3 at 110°C. On the other hand, the derivatives 28a-c were obtained by treating 26a-c with trifluoroacetic acid followed by the reaction with appropriate amines in isopropanol [45,46].…”

Section: Synthetic Pathways Of Triazoloquinazolines and Derivativesmentioning

confidence: 99%

Triazoloquinazoline: Synthetic Strategies and Medicinal Importance

Jabeen,

Aslam,

Ahmad

et al. 2023

Recent Advances on Quinazoline

View full text Add to dashboard Cite

Triazoloquinazoline is a fused heterocyclic nucleus, formed by the fusion of two fundamental heterocyclic moieties; triazole and quinazoline. This class of compound is known for its potential as a therapeutic agent and is endowed with several pharmacological applications. Triazoloquinazoline and its derivatives have shown a variety of biological applications such as anticancer, anti-inflammatory, antimicrobial, antiviral, antihypertensive, anticonvulsant, antidiabetic, antioxidant, adenosine receptor antagonist, and significant cytotoxic activities. Hence, this privileged scaffold could act as an important candidate in the field of drug development. Many synthetic protocols have been developed to efficiently synthesize this fused heterocycle and its derivatives. Triazole and quinazoline rings fused at different positions which occurs in various isomeric forms such as, 1,2,4-triazolo[1,5-c]quinazoline, 1,2,4-triazolo[1,5-a]quinazoline, 1,2,4-triazolo[4,3-c]quinazoline, 1,2,4-triazolo[4,3-a]quinazoline, etc. This book chapter covers the synthesis of various isomeric forms of triazoloquinazoline as well as their biological activities.

show abstract

“…The role of DNA-interfering compounds has different approaches to exert their anticancer activities involving intercalating with the DNA and/or enzymes necessary for relevant DNA functions giving rise to a cellular response change which leads to cell death 3 . Typical DNA intercalators are compounds characterized by their ability to be inserted perpendicularly into DNA to form a DNA-intercalator complex stabilized by different hydrophobic stackings without forming covalent bonds 4 . Polycyclic aromatic hydrocarbons have become one of the key molecular objectives in anticancer activity owing to their ability to be inserted between stacked base pairs of DNA 5 .…”

Section: Introductionmentioning

confidence: 99%

New imidazole-2-thiones linked to acenaphythylenone as dual DNA intercalators and topoisomerase II inhibitors: structural optimization, docking, and apoptosis studies

Mohamed,

Alshammari,

Aly

et al. 2024

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2 H )-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin , respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.

show abstract

New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies

Cited by 6 publications

References 74 publications

Novel 2‐[thio]acetamide linked quinazoline/1,2,4‐triazole/chalcone hybrids: Design, synthesis, and anticancer activity as EGFR inhibitors and apoptotic inducers

Novel 2‐[thio]acetamide linked quinazoline/1,2,4‐triazole/chalcone hybrids: Design, synthesis, and anticancer activity as EGFR inhibitors and apoptotic inducers

Triazoloquinazoline: Synthetic Strategies and Medicinal Importance

New imidazole-2-thiones linked to acenaphythylenone as dual DNA intercalators and topoisomerase II inhibitors: structural optimization, docking, and apoptosis studies

Contact Info

Product

Resources

About