Design and synthesis of novel 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivatives as antiproliferative EGFR and BRAFV600E dual inhibitors

Al-Wahaibi, Lamya H.; Gouda, Ahmed M.; Abou-Ghadir, Ola F.; Salem, Ola I. A.; Ali, Asmaa T.; Farghaly, Hatem S.; Abdelrahman, Mostafa H.; Trembleau, Laurent; Abdu-Allah, Hajjaj H.M.; Youssif, Bahaa G.M.

doi:10.1016/j.bioorg.2020.104260

Cited by 57 publications

(55 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EGFR-TK assay was performed to evaluate the inhibitory potency of novel compound 1 against the EGFR [33]. For full methodology see the Supplementary File.…”

Section: Egfr Inhibition Activitymentioning

confidence: 99%

Chemical Constituent Profiling of Phyllostachys heterocycla var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells

et al. 2021

View full text Add to dashboard Cite

Different extracts of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens were screened against panel of cancer cell lines and normal one. The cell viability results exhibited that the ethyl acetate extract showed the least vitality percentage of 2.14% of HepG2 cells. Accordingly, it was subjected to chromatographic separation, which resulted in the isolation of a new natural product; 7-hydroxy, 5-methoxy, methyl cinnamate (1), together with four known compounds. The structures of the pure isolated compounds were deduced based on different spectroscopic data. The new compound (1) was screened against the HepG2 and MCF-7 cells and showed IC50 values of 7.43 and 10.65 µM, respectively. It induced apoptotic cell death in HepG2 with total apoptotic cell death of 58.6% (12.44-fold) compared to 4.71% in control by arresting cell cycle progression at the G1 phase. Finally, compound 1 was validated as EGFR tyrosine kinase inhibitor in both enzymatic levels (IC50 = 98.65 nM compared to Erlotinib (IC50 = 78.65 nM). Finally, in silico studies of compound 1 through the molecular docking indicated its high binding affinity towards EGFR protein and the ADME pharmacokinetics indicated it as a drug-like.

show abstract

“…EGFR-TK assay was performed to evaluate the inhibitory potency of novel compound 1 against the EGFR [33]. For full methodology see the Supplementary File.…”

Section: Egfr Inhibition Activitymentioning

confidence: 99%

Chemical Constituent Profiling of Phyllostachys heterocycla var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Compounds 5a – n showed a number of inhibitory profiles against the transmembrane tumor-associated isoform hCA IX. Compounds 5g , 5b , 5d , 5e , 5j and 5n had sub micromolar inhibitory potencies against hCA IX (Kis) of 0.32, 0.36, 0.72, 0.84, 1.10, and 1.3 μM, respectively, with a pronounced selectivity for hCA IX over hCA XII (12, 11.50, 7.00, 6.50, 5.60, and 5.0, respectively) in comparison to AAZ (selectivity ratio for hCA IX over hCA XII = 0.20) [ 20 , 21 ]. In addition, compounds 5a – n displayed a variable degree of inhibition against the other transmembrane tumor-associated isoform, hCA XII, with Kis below 7 μM for all these compounds.…”

Section: Resultsmentioning

confidence: 99%

“…Cell viability assay was carried out using human mammary gland epithelial cell line (MCF-10A) [ 20 ]. MCF-10A cells were incubated with compounds 5b , 5d , 5e , 5g , 5j and 5n for 4 days and MTT assay [ 21 ] was used to determine the viability of cells. See Appendix A .…”

Section: Methodsmentioning

confidence: 99%

“…MTT assay was carried out to study the effect of compounds on mammary epithelial cells (MCF-10A) [ 20 , 21 ]. The medium in which cells were propagated contained Dulbecco’s modified Eagle’s medium (DMEM)/Ham’s F-12 medium (1:1) supplemented with epidermal growth factor (20 ng/mL), hydrocortisone (500 ng/mL), insulin (10 μg/mL), 2 mM glutamine and 10% fetal calf serum.…”

Section: Appendix A1 Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors

et al. 2021

Self Cite

View full text Add to dashboard Cite

A novel series of tri-aryl imidazole derivatives 5a–n carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA IX and XII activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of 5g > 5b > 5d > 5e > 5g > 5n (Ki = 0.3–1.3 μM, and selectivity ratio for hCA IX over hCA XII = 5–12) relative to acetazolamide (Ki = 0.03 μM, and selectivity ratio for hCA IX over hCA XII = 0.20). The previous sixth inhibitors have been further investigated for their anti-proliferative activity against four different cancer cell lines using MTT assay. Compounds 5g and 5b demonstrated higher antiproliferative activity than other tested compounds (with GI50 = 2.3 and 2.8 M, respectively) in comparison to doxorubicin (GI50 = 1.1 M). Docking studies of these two compounds adopted orientation and binding interactions with a higher liability to enter the active side pocket CA-IX selectively similar to that of ligand 9FK. Molecular modelling simulation showed good agreement with the acquired biological evaluation.

show abstract

“…Thus, materials obtained by these molecules could be versatile [ 41 ]. There is growing interest in CDPs, and recent reviews exist that discuss their bioactivity [ 58 , 61 , 62 ], supramolecular organization [ 31 , 40 ], and use as scaffolds for drug discovery [ 52 , 63 , 64 , 65 , 66 ].…”

Section: Introductionmentioning

confidence: 99%

Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

Scarel

Marchesan

2021

Molecules

View full text Add to dashboard Cite

Cyclodipeptides (CDPs) or 2,5-diketopiperazines (DKPs) can exert a variety of biological activities and display pronounced resistance against enzymatic hydrolysis as well as a propensity towards self-assembly into gels, relative to the linear-dipeptide counterparts. They have attracted great interest in a variety of fields spanning from functional materials to drug discovery. This concise review will analyze the latest advancements in their synthesis, self-assembly into gels, and their more innovative applications.

show abstract

Design and synthesis of novel 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivatives as antiproliferative EGFR and BRAFV600E dual inhibitors

Cited by 57 publications

References 42 publications

Chemical Constituent Profiling of Phyllostachys heterocycla var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells

Chemical Constituent Profiling of Phyllostachys heterocycla var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors

Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

Contact Info

Product

Resources

About