Abstract:A one-pot three-component reaction of o-formyl carbamate, a primary amine, a nucleophile (1H-indole or 2-napthol) in water generated a variety of functionalised 3,4-dihydroquinazolin-2(1H)-one derivatives.
“…A bunch of methods has been proposed to synthesize 3,4-dihydroquinazolinones with plausible yields. Take the examples of the multicomponent reaction (MCR) protocols investigated by Luke R. Odell et al [ 36 , 37 ], an organo-catalyzed enantioselective approach for the synthesis of chiral trifluoromethyl dihydroquinazolinones, as a biologically important scaffold, by Xie et al [ 38 ], and the catalyst-free and hydrophobically-directed approach for the production of functionalized 3,4-dihydroquinazolin-2(1H)-one by Chandrasekharam et al [ 39 ]. Fig.…”
Background
Cancer is the most cause of morbidity and mortality, and a major public health problem worldwide. In this context, two series of quinazolinone 5a–e and dihydroquinazolinone 10a–f compounds were designed, synthesized as cytotoxic agents.
Methodology
All derivatives (5a–e and 10a–f) were synthesized via straightforward pathways and elucidated by FTIR, 1H-NMR, CHNS elemental analysis, as well as the melting point. All the compounds were evaluated for their in vitro cytotoxicity effects using the MTT assay against two human cancer cell lines (MCF-7 and HCT-116) using doxorubicin as the standard drug. The test derivatives were additionally docked into the PARP10 active site using Gold software.
Results and discussion
Most of the synthesized compounds, especially 5a and 10f were found to be highly potent against both cell lines. Synthesized compounds demonstrated IC50 in the range of 4.87–205.9 μM against HCT-116 cell line and 14.70–98.45 μM against MCF-7 cell line compared with doxorubicin with IC50 values of 1.20 and 1.08 μM after 72 h, respectively, indicated the plausible activities of the synthesized compounds.
Conclusion
The compounds quinazolinone 5a–e and dihydroquinazolinone 10a–f showed potential activity against cancer cell lines which can lead to rational drug designing of the cytotoxic agents.
“…A bunch of methods has been proposed to synthesize 3,4-dihydroquinazolinones with plausible yields. Take the examples of the multicomponent reaction (MCR) protocols investigated by Luke R. Odell et al [ 36 , 37 ], an organo-catalyzed enantioselective approach for the synthesis of chiral trifluoromethyl dihydroquinazolinones, as a biologically important scaffold, by Xie et al [ 38 ], and the catalyst-free and hydrophobically-directed approach for the production of functionalized 3,4-dihydroquinazolin-2(1H)-one by Chandrasekharam et al [ 39 ]. Fig.…”
Background
Cancer is the most cause of morbidity and mortality, and a major public health problem worldwide. In this context, two series of quinazolinone 5a–e and dihydroquinazolinone 10a–f compounds were designed, synthesized as cytotoxic agents.
Methodology
All derivatives (5a–e and 10a–f) were synthesized via straightforward pathways and elucidated by FTIR, 1H-NMR, CHNS elemental analysis, as well as the melting point. All the compounds were evaluated for their in vitro cytotoxicity effects using the MTT assay against two human cancer cell lines (MCF-7 and HCT-116) using doxorubicin as the standard drug. The test derivatives were additionally docked into the PARP10 active site using Gold software.
Results and discussion
Most of the synthesized compounds, especially 5a and 10f were found to be highly potent against both cell lines. Synthesized compounds demonstrated IC50 in the range of 4.87–205.9 μM against HCT-116 cell line and 14.70–98.45 μM against MCF-7 cell line compared with doxorubicin with IC50 values of 1.20 and 1.08 μM after 72 h, respectively, indicated the plausible activities of the synthesized compounds.
Conclusion
The compounds quinazolinone 5a–e and dihydroquinazolinone 10a–f showed potential activity against cancer cell lines which can lead to rational drug designing of the cytotoxic agents.
“…26 This is a simple, highly attractive approach for accessing novel and densely substituted DHQ analogues, based on an array of different chemistries (Scheme 1). [27][28][29][30][31] During the course of our investigations on the reactivity of Nacyliminium ions (I), we observed the formation of an unknown side-product (4a) when formic acid was used as a solvent, in an aza-Henry based cyclization cascade, in lieu of acetic acid (Scheme 1). Subsequent characterization studies revealed that this compound retained the DHQ core but lacked the expected C4-substituent.…”
“…During the preparation of this manuscript, Chandrasekharam and co-workers reported a water-mediated multicomponent synthesis of 4-aryl substituted 3,4-dihydroquinazolinones under conventional heating. 24 However, it is important to highlight that the use of water as a reaction medium demanded long reaction times, and, in many cases, chromatographic purification was required, both of which detract from its appeal as a green protocol. Moreover, the scope of this method is restricted to indole and mono-functional amine nucleophiles, limiting its utility in library generation.…”
A one-pot
microwave-assisted
aza
-Friedel–Crafts
arylation of
N
-acyliminium ions, generated in situ
from
o
-formyl carbamates and different amines, is
reported. This metal-free protocol provides rapid access to diverse
4-aryl 3,4-dihydroquinazolinones in excellent yield without any aqueous
workup. A solvent-directed process for the selective
aza
-Friedel–Crafts arylation of electron-rich aryl/heteroaryl/butenyl-tethered
N
-acyliminium ions is also described.
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