Pyrimidoquinoline Derivatives Research Articles

Synthesis and Antitumor Activity Evaluation of Novel Pyrimidoquinoline Derivatives

Quinoline-based structures possess various types of biological activities and recently have attracted attention as an antitumor scaffold via different known anti-cancer mechanisms. In this study, a novel series of tetrahydropyrimido[4,5-b]quinoline-4,6(3H,7H)-diones (7a-r) were synthesized and evaluated for their in vitro cytotoxic effects on breast cancer cells (MCF-7 cells), prostate cancer cells (LNCaP cells), and normal human adult dermal fibroblast (HDF) cells. Among them, the compounds (7c), (7d), (7 g), (7j), (7k), (7 l), and (7r) showed high activity against LNCaP and MCF-7 cancer cells with IC50 values ranging from 37.62 to 67.3 µM, compared to etoposide as reference drug. The compound (7 l) was the most active compound against LNCaP cancer cells and was examined for further 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining which confirmed apoptosis and DNA damage in LNCaP cells. The study showed upregulation of Bax and downregulation of Bcl-2 as two potential markers of an intrinsic pathway of apoptosis in LNCaP cell line by using quantitative real-time PCR (qRT-PCR) method. Finally, we found that compound 7I can be considered as a potential agent for induction of apoptosis in cancer cells (LNCaP cells).

Modified Biginelli Reaction: Synthesis of Pyrimidoquinoline Derivatives

Compounds having quinolone and pyrimidine skeleton plays an important role in the medicinal chemistry. The objective of the present work was to modify the Biginelli reaction by using heterocylic ketones under microwave condition. We have demonstrated new synthetic route of quinolone fused 1,4-dipyrimidines by the reaction of 6-methyl-4-hyrdoxyquinolin-2(1H)-one (1), substituted aromatic aldehydes (2a-g) with phenyl urea (3). The structure of these newly synthesized compounds was characterized IR, NMR, Mass spectral and elemental analysis.

ChemInform Abstract: Efficient Syntheses of Fluorine‐Containing Pyrimido[5,4‐c]quinolines and Benzo[h][1,6]naphthyridines by Condensation Reactions of 3‐Trifluoroacetylquinolin‐4‐amine with Aldehydes and Ketones.

Abstract3‐Trifluoroacetyl‐4‐aminoquinoline (I) undergoes a three‐component condensation reaction with aldehydes ammonia to afford pyrimidoquinoline derivatives as single or major products.

ChemInform Abstract: A Green Multicomponent Synthesis of Bioactive Pyrimido[4,5‐b]quinoline Derivatives as Antibacterial Agents in Water Catalyzed by RuCl3·xH2O.

AbstractSome of the synthesized pyrimidoquinoline derivatives (IV) (20 examples) exhibit good to excellent antibacterial activity.

Anticancer and radiosensitizing evaluation of novel sulfonamides with quinoline and pyrimidoquinoline groups

Because of the reported anticancer activity of quinolines and pyrimidoquinolines containing the biologically active sulfonamide moiety, a new series of quinoline and pyrimidoquinoline derivatives were synthesized and tested for in-vitro anticancer activity against liver-cancer cells. Reaction of 5,5-dimethylcyclohexane-1,3-dione 1 with sulfanilamide 2 in ethanol yielded the corresponding enaminone 3. Treatment of enaminone 3 with 2-(4-methylbenzylidene)malononitrile 4 gave the corresponding strategic starting material quinoline 6. The quinoline-o-aminocarbonitrile 6 was used to synthesize new series of quinolines 8, 11, 15–20 and pyrimidoquinolines 7, 10, 12–14. The structures of the synthesized compounds were confirmed by microanalysis, IR, 1H NMR, and 13C NMR spectroscopy, and use of mass spectral data. Almost all the compounds had significant activity against human cancer cell line HEPG2 compared with doxorubicin as a positive control. The most potent compounds, 7, 10, and 20, were also evaluated for their ability to enhance the killing effect of γ-radiation.

Novel brominated quinoline and pyrimidoquinoline derivatives as potential cytotoxic agents with synergistic effects of γ-radiation

New quinoline derivatives 6, 7 and 19, pyrimidoquinoline derivatives 8-16 and triazolopyrimidoquinoline derivatives 17 and 18 bearing a bromo-substituent were synthesized starting from 3-(4-Bromophenylamino)-5,5-dimethylcyclohex-2-enone 3. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 9, 11, 17 and 18 showed IC(50) values (36.4, 39.7, 39.02 and 36.4 μM, respectively) comparable to that of the reference drug doxorubicin (IC(50) = 32.02 μM). On the other hand, compound 6, 14 and 19 exhibited better activity than doxorubicin with IC(50) values of 8.5, 23.5 and 23.7 μM. Additionally, the most potent compounds 6, 14 and 19 were evaluated for their ability to enhance the cell killing effect of γ-radiation.

ChemInform Abstract: Facile Synthesis of Some New Pyrimidoquinolines

Abstractvia rearrangement of N‐quinolinyl isoxazolones (III) under mild base‐catalyzed conditions

ChemInform Abstract: Design and Synthesis of Some Novel Quinoline Derivatives as Anticancer and Radiosensitizing Agents Targeting VEGFR Tyrosine Kinase.

AbstractA variety of novel quinoline and pyrimidoquinoline derivatives (XVI) is synthesized from enaminone (I), and evaluated for in vitro effects against the human cancer cell line MCF7.

Facile Synthesis of Some New Pyrimidoquinolines

The reaction of ethyl 5-oxo-2,5-dihydroisoxzole-4-carboxylate with derivatives of 2-chloroquinoline afforded the desired N-quinolinyl isoxazolones. Their reactions with triethylamine in chloroform produced the corresponding pyrimidoquinoline derivatives, through intramolecular cyclization.

Synthesis of Some Pyrimido[4,5-b]quinoline Derivatives

A series of pyrimidoquinoline derivatives was synthesized in good yield and short reaction times by reaction of 3-arylaminoisoxazol-5(2H)-ones with derivatives of 2-chloro-3-formylquinoline in toluene under reflux conditions.

Synthesis, in vitro antimicrobial and in vivo antitumor evaluation of novel pyrimidoquinolines and its nucleoside derivatives

Seven series of pyrimidoquinoline derivatives have been synthesized, tetrazolo[4′,3′:-1,2]pyrimido[4,5-b]quinoline (3), 2-aminopyrimido[4,5-b]quinoline (4), triazolo[4′,3′:1,2]-pyrimidoquinoline (5a,b, 10), imidazolo[3′,2′:1,2]pyrimido[4,5-b]-quinoline (8a,b), 6-chloro-2-methylthiopyrimido[4,5-b]quinoline (12), acetylated nucleosides (16, 17a,b) and deacetylated nucleosides (18, 19a,b). Some of the novel pyrimidoquinoline derivatives possess highly activity toward the bacteria and fungi species. The new quinolines derivatives were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute (NCI). Most of them had excellent growth inhibition activity, having LD50 values in the low micromolar to nanomolar concentration range.

Synthesis, antioxidant and toxicological study of novel pyrimido quinoline derivatives from 4-hydroxy-3-acyl quinolin-2-one

A series of novel pyrimido and other fused quinoline derivatives like 4-methyl pyrimido [5,4- c]quinoline-2,5(1 H,6 H)-dione ( 4a), 4-methyl-2-thioxo-1,2-dihydropyrimido [5,4- c]quinoline-5(6 H)-one ( 4b), 2-amino-4-methyl-1,2-dihydropyrimido [5,4- c]quinolin-5(6 H)-one ( 4c), 3-methylisoxazolo [4,5- c]quinolin-4(5 H)-one ( 4d), 3-methyl-1 H-pyrazolo [4,3- c]quinoline-4(5 H)-one ( 5e), 5-methyl-1 H-[1,2,4] triazepino [6,5- c]quinoline-2,6(3 H,7 H)-dione ( 5f), 5-methyl-2-thioxo-2,3-dihydro-1 H-[1,2,4]triazepino [6,5- c]quinolin-6(7 H)-one ( 5g) were synthesized regioselectively from 4-hydroxy-3-acyl quinolin-2-one 3. They were screened for their in vitro antioxidant activities against radical scavenging capacity using DPPH , Trolox equivalent antioxidant capacity (TEAC), total antioxidant activity by FRAP, superoxide radical ( O 2 ° - ) scavenging activity, metal chelating activity and nitric oxide scavenging activity. Among the compounds screened, 4c and 5g exhibited significant antioxidant activities.

ChemInform Abstract: Synthesis and Docking Studies of Some Novel Quinoline Derivatives Bearing a Sulfonamide Moiety as Possible Anticancer Agents.

AbstractMost of the synthesized novel quinoline and pyrimidoquinoline derivatives show significant anticancer activities against breast cancer cell line.

Docking study, in vitro anticancer screening and radiosensitizing evaluation of some new fluorine-containing quinoline and pyrimidoquinoline derivatives bearing a sulfonamide moiety

The present work reports the synthesis of 20 novel fluorine-containing quinoline and pyrimido[4,5-b]quinoline derivatives bearing a sulfonamide moiety. The new synthesized compounds were designed in compliance with the general pharmacophoric requirements for carbonic anhydrase (CA) inhibiting anticancer drugs, as this may play a role in their anticancer activity. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 11 and 12 exhibited better activities than the reference drug doxorubicin (IC50 = 71.8 μM) with IC50 values of 52.6 μM and 67.3 μM, respectively. On the other hand, compounds 6, 10, and 13 showed IC50 values (71.8 μM, 69.8 μM, and 70.8 μM, respectively) comparable to that of the reference drug doxorubicin. In addition, docking of the synthesized compounds into human carbonic anhydrase isozyme II (hCA II) active site was performed in order to predict the affinity and the orientation of these compounds at the isozyme active site. Also, the most active compounds, 11 and 12, were selected and evaluated for their ability to enhance the cell killing effect of γ-radiation.

An Efficient One‐Pot Synthesis of Novel Pyrimidoquinoline Derivatives under Microwave Irradiation Without Catalyst.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An efficient one-pot synthesis of novel pyrimidoquinoline derivatives under microwave irradiation without catalyst

A series of pyrimidoquinoline derivatives were synthesized through one-pot condensation of 2,6-diaminopyrimidin-4-one, aldehyde and cyclic a 1,3-dicarbonyl compound in glycol under microwave irradiation without catalyst. The protocol in the absence of catalyst has the advantage of good yield (87-95%), short reaction time (4-7 min) and an environmentally friendly technique.

Synthesis of some novel quinoline-3-carboxylic acids and pyrimidoquinoline derivatives as potential antimicrobial agents.

The synthesis and in vitro antimicrobial evaluation of several quinoline and pyrimidoquinoline derivatives are described. Treatment of 7-substituted quinolin-2(1H)-one-3-carboxylic acids 2a-c with phosphoryl chloride or thionyl chloride gave rise to the 7-substituted 2-chloroquinoline-3-carboxylic acids 3a-c and 7-substituted 2-chloro-3-chlorocarbonylquinolines 5a-c respectively. The 2-chloro function in compounds 3a-c was replaced by 2-aminothiazole or 2-aminopyridine to give 2-(thiazol-2-yl)aminoquinoline-3-carboxylic acids 4a-c or 2-(pyrid-2-yl)aminoquinoline-3-carboxylic acids 4d-f. Treatment of 5a-c with the same heterocyclic amines at room temperature furnished the corresponding 7-substituted 2-chloro-3-heteryl-aminocarbonylquinolines 6a-f. The tetracyclic 9-substituted thiazolo[3', 2':1, 2]-pyrimido[4, 5-b]quinolin-5-ones 7a-c and 10-substituted pyrido[1', 2':1, 2]-pyrimido[4, 5-b]quinolin-6-ones 7d-f were synthesized by heating 5a-c with the heterocyclic amines in toluene or by heating 6a-f under reflux in dimethylformamide. The products were evaluated in vitro for potential antimicrobial activity.

Peculiar reaction behaviour of barbituric acid derivatives towards aromatic amines

5-Benzoylethyl barbituric acid derivatives 2a-c were prepared as useful precursors for the synthesis of pyrimidine fused heterocycles. Their behaviour as 1,5-diketocompounds towards aniline derivatives afforded the pyrimidoquinoline derivatives 6a-e. On the other hand, fusion of o -substituted anilines with 1,3-dimethyl barbituric acid derivatives 8a,b gave the corresponding benzazoles 10a-e. Furthermore, the reaction of 1,3-dimethyl barbituric acid ( 1) with catechol/K 3|Fe(CN) 6| or β-ketoester ( 19)/SiCl 4 gave the benzofuro adduct 13a and the diphenylphenyl barbituric acid derivative 18, respectively.