In-vitro cytotoxic and radiosensitizing evaluation of novel 2-pyridone, isoquinoline, chromene and chromenopyridone derivatives

Alsaid, Mansour S.; El‐Gazzar, Marwa G.; Ghorab, Mostafa M.

doi:10.5155/eurjchem.3.2.228-234.596

Cited by 8 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To a stirred solution of cyanoacetic acid (100 mg, 1.18 mmol) in CH 2 Cl 2 (5 mL) were added corresponding aniline (1.18 mmol), EDC·HCl (450 mg, 2.35 mmol), and DMAP (29 mg, 0.24 mmol). The resulting mixture was stirred at room temperature for 24 h. The volatiles were evaporated, and the residue was chromatographed using column chromatography (SiO 2 , hexane/acetone = 5:1–1:1) to afford the corresponding amides ( 1a–g , 1h , 1i , 1j–k , 1l , 1m , 1n–p , 1q , 1r , 1s , 1t , 1u , 1v – w , 1x ) as a colorless solid.…”

Section: Methodsmentioning

confidence: 99%

Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer

et al. 2020

View full text Add to dashboard Cite

Aldo–keto reductase (AKR) 1C3 catalyzes the synthesis of active androgens that promote the progression of prostate cancer. AKR1C3 also contributes to androgen-independent cell proliferation and survival through the metabolism of prostaglandins and reactive aldehydes. Because of its elevation in castration-resistant prostate cancer (CRPC) tissues, AKR1C3 is a promising therapeutic target for CRPC. In this study, we found a novel potent AKR1C3 inhibitor, N-(4-fluorophenyl)-8-hydroxy-2-imino-2H-chromene-3-carboxamide (2d), and synthesized its derivatives with IC50 values of 25–56 nM and >220-fold selectivity over other AKRs (1C1, 1C2, and 1C4). The structural factors for the inhibitory potency were elucidated by crystallographic study of AKR1C3 complexes with 2j and 2l. The inhibitors suppressed proliferation of prostate cancer 22Rv1 and PC3 cells through both androgen-dependent and androgen-independent mechanisms. Additionally, 2j and 2l prevented prostate tumor growth in a xenograft mouse model. Furthermore, the inhibitors significantly augmented apoptotic cell death induced by anti-CRPC drugs (abiraterone or enzalutamide).

show abstract

Section: Methodsmentioning

confidence: 99%

Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…On the other hand, 2-pyridones and their derivatives play an essential role in medicinal chemistry and are proven to possess several biological properties; ,− thus, despite the large number of methods known for their synthesis, new procedures are required to be developed. Many catalysts have been used in the synthesis of 2-pyridinone from 1,3-diketones, such methanesulfonic acid, SiO 2 , and triethylamine or piprazine .…”

Section: Introductionmentioning

confidence: 99%

Ultrasonically Assisted N-Cyanoacylation and Synthesis of Alkyl(4-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)benzoyl)amino Acid Ester Derivatives

2020

View full text Add to dashboard Cite

This work represents the use of N-3-(3,5-dimethyl-1Hpyrazol-1-yl)-3-oxopropanenitrile as a cyanoacetylating agent for the synthesis of cyanoacetamide benzoic acid and benzophenone derivatives by two different methods, namely, conventional heating and ultrasonication. The cyanoacetamide derivatives were subjected to cyclization to produce N-substituted 2-pyridone derivatives under conventional heating and by an ultrasonic method as well. The ultrasonic method afforded the products in less reaction time with high yields and purities compared to the conventional method, as observed from their spectral data. N-(4-Carboxy phenyl)-4,6-dimethyl-3-cyano-2-pyridone was coupled with different amino acid esters by the OxymaPure/DIC methodology under traditional and ultrasonic conditions. Again, ultrasonication assisted the coupling step and afforded the products with higher yields and purities compared to the traditional method. Fourier transform infrared spectroscopy, NMR ( 1 H and 13 C), elemental analysis, and LC−MS were used to determine the structures of all compounds. Finally, a feature of this protocol is exploring the utilization of ultrasonication as an eco-friendly alternative conventional heating method for N-cyanoacylation and synthesis of N-substituted pyridinone derivatives and as a coupling method for the formation of an amide bond, which might be of interest for many researchers.

show abstract

Computer-aided anticancer drug design: In vitro and in silico studies of new iminocoumarin derivative

Kecel‐Gunduz

Budama‐Kilinc

Gök

et al. 2021

Journal of Molecular Structure

View full text Add to dashboard Cite

In-vitro cytotoxic and radiosensitizing evaluation of novel 2-pyridone, isoquinoline, chromene and chromenopyridone derivatives

Cited by 8 publications

References 18 publications

Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer

Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer

Ultrasonically Assisted N-Cyanoacylation and Synthesis of Alkyl(4-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)benzoyl)amino Acid Ester Derivatives

Computer-aided anticancer drug design: In vitro and in silico studies of new iminocoumarin derivative

Contact Info

Product

Resources

About