Pyrrolo[3,2‐<i>h</i>]quinazolines as Photochemotherapeutic Agents

Barraja, Paola; Caracausi, Libero; Diana, Patrizia; Montalbano, Alessandra; Carbone, Anna; Salvador, Alessia; Brun, Paola; Castagliuolo, Ignazio; Tisi, Silvia; Dall’Acqua, Francesco; Vedaldi, Daniela; Cirrincione, Girolamo

doi:10.1002/cmdc.201100085

Cited by 50 publications

(25 citation statements)

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“…Anticancer agent Iressa (ZD1839) A is a clinically approved example of quinazoline-based inhibitors which is in phase III clinical trials for cancer used to inhibit the receptor tyrosine kinase of epidermal growth factor. also exhibit pronounced biological activities as antimicrobial, 7,8 anti-HIV (NNRTI), 9,10 anti-tumour, [11][12][13][14][15][16] potential analgesic and anti-inflammatory activity. 17 Non-proteinogenic amino acids are major component in a number of drugs including β-lactam antibiotics 18 and glutamate antagonists.…”

Section: Introductionmentioning

confidence: 99%

“…The mixture was kept at -5 º C for 24 hrs., then at 25 º C for another 24 hrs., followed by washing with 0.5 N HCl, water, 3% solution of NaHCO3 and finally dried (Na2SO4). The solution was evaporated to dryness, and the residue was recrystallized from petroleum ether/ ethyl acetate to give the corresponding quinazoline dipeptide of dione derivative (16) 3H, s, OCH3), 3.52-3.46 (2H, m, NHCH2), 2.50-2.46 (2H, t, J 6.0 Hz, CH2). The initial structures of 3a was edited by an Avogadro package 53 The structure was optimized using the DFT calculations at the B3LYP level of theory employing 6-311G basis set.…”

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confidence: 99%

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Synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate

Ismail¹,

Ali²,

Fathalla³

et al. 2017

Arkivoc

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A series of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate 10-13a-f has been developed on the basis of the N-chemoselective reaction of 3-substituted quinazoline-2,4-diones 3a-d with ethyl chloroacetate and azide coupling method with amino acid ester hydrochloride. The precursor quinazoline diones 3a-d chemoselective reactions were studied using DFT(B3LYP)/6-311G level of theory and were prepared by a new rearrangement method from the corresponding 2-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio) acetohydrazide 6.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate

Ismail¹,

Ali²,

Fathalla³

et al. 2017

Arkivoc

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“…[87] Indole ethyl isothiocyanates were investigated due to their similarity to benzyl isothiocyantes and phenyl ethyl isothiocyanes, both of which have been reported to have anti-cancer activity in a range of cancers. [6,[88][89][90] Of all the indole ethyl isothiocyanates tested, 7-methyl indole-3-ethyl isothiocyanate (7Me-IEITC, Figure 19) was found to be the most active, and when tested on a range of neuroblastoma cell lines was found to have an IC50 in the range of 2.5-5 µM, while not affecting the primary control cells. 7Me-IEITC activates the apoptoptic markers caspase-3, caspase-8 and caspase-9, activates the pro-apoptoptic p38 mitogen-activated protein kinases and signaling pathway SAPK/JNK, and downregulates AKT.…”

Section: Ros Producersmentioning

confidence: 99%

Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives

Sherer

Snape

2015

European Journal of Medicinal Chemistry

134

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HIGHLIGHTS• Brain cancer mortality rates are much higher than mortality rates for cancers of other sites. •Due to the blood brain barrier, many drugs that work on cancers of other sites do not work on brain cancers • Indoles, carbazoles and indolocarbazoles make good scaffolds for drugs to be built up around due to their rigidity, planarity and ease of synthesis. GRAPHICAL ABSTRACT ACRONYMS/INITIALISMSAML -Acute myeloid leukaemia CK2 -Casein kinase 2 CNS -Central nervous system PARP -Poly ADP ribose polymerase PDGF -Platelet-derived growth factor PKC -Protein kinase C ROS -Reactive oxygen species VEGF -Vascular endothelial growth factor ABSTRACT Tumours of the central nervous system are intrinsically more dangerous than tumours at other sites, and in particular, brain tumours are responsible for 3% of cancer deaths in the UK. Despite this, research into new therapies only receives 1% of national cancer research spend. The most common chemotherapies are temozolomide, procarbazine, carmustine, lomustine and vincristine, but because of the rapid development of chemoresistance, these drugs alone simply aren't sufficient for longterm treatment. Such poor prognosis of brain tumour patients prompted us to research new treatments for malignant glioma, and in doing so, it became apparent that aromatic heterocycles play an important part, especially the indole, carbazole and indolocarbazole scaffolds. This review highlights compounds in development for the treatment of tumours of the central nervous system which are structurally based on the indole, carbazole and indolocarbazole scaffolds, under the expectation that it will highlight new avenues for research for the development of new compounds to treat these devastating neoplasms.

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“…To overcome some of the disadvantages of classical thymidylate synthase inhibitors, our team has tried to synthesize novel 5-amino-2-(4-chlorophenyl)-7-substituted phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo (3,2-α)pyrimidine-6-carbonitrile derivatives. Pyrimidine and its derivatives have been recognized as important heterocyclic compounds due to their variety of chemical and biological significance to medicinal chemistry [12][13][14][15]. Hybridization of two different bioactive molecules with complementary pharmacophoric functions often showed synergistic effects [16,17].…”

Section: Introductionmentioning

confidence: 99%

Ultrasound Mediated One-Pot, Three Component Synthesis, Docking and ADME Prediction of Novel 5-Amino-2-(4-chlorophenyl)-7-Substituted Phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile Derivatives as Anticancer Agents

Tiwari¹,

Seijas

Vázquez-Tato

et al. 2016

Molecules

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Herein, we report an environmentally friendly, rapid, and convenient one-pot ultrasoundpromoted synthesis of 5-amino-2-(4-chlorophenyl)-7-substituted phenyl-8,8a-dihydro-7H-(1,3,4) thiadiazolo(3,2-α)pyrimidine-6-carbonitrile derivatives. The in-vitro anticancer activities of these compounds were evaluated against four human tumor cell lines. Among all the synthesized derivatives, compound 4i, which has substituent 3-hydroxy-4-methoxyphenyl is found to have the highest GI 50 value of 32.7 µM, 55.3 µM, 34.3 µM, 28.9 µM for MCF-7, K562, HeLa and PC-3 cancer cell lines respectively. A docking study of the newly synthesized compounds were performed, and the results showed good binding mode in the active site of thymidylate synthase enzyme. ADME properties of synthesized compounds were also studied and showed good drug like properties.

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Pyrrolo[3,2‐h]quinazolines as Photochemotherapeutic Agents

Cited by 50 publications

References 29 publications

Synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate

Synthesis of methyl [3-alkyl-2-(2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl)-acetamido] alkanoate

Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives

Ultrasound Mediated One-Pot, Three Component Synthesis, Docking and ADME Prediction of Novel 5-Amino-2-(4-chlorophenyl)-7-Substituted Phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile Derivatives as Anticancer Agents

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