Synthesis and cytotoxic evaluation of novel quinozalinone derivatives with substituted benzimidazole in position 3.

Quinazolinone and benzimidazole are both fused heterocyclic compounds which have shown valuable biological properties including cytotoxic, antibacterial, and antifungal activities. In this study, a series of novel quinazolinone derivatives substituted with benzimidazole were synthesized in two parts. In the first part 2 - phenyl - 1H - benzimidazol - 6 - amine (4) was synthesized from the reaction of 4-nitro-o-phenylenediamine and benzoic acid. In the second part, new 3-(2-phenyl-1H benzoimidazol-5-yl)- 3H-quinazolin-4-one derivatives (8a-8f) were also prepared. Finally compound 4 was reacted with the different benzoxazinone derivatives (8a-8f) to give the target compounds. The structures of the synthesized compounds were confirmed by IR and 1HNMR. Cytotoxic activities of the final compounds were assessed at 100, 200, 300, 400, and 500 µM against MCF-7 and HeLa cell lines using the MTT colorimetric assay. Almost all compounds exhibited good cytotoxic activity against both cell lines. Compound 9d demonstrated the highest cytotoxic activity against MCF7 and Hela cell lines with IC50 70 µM and 50 µM, respectively.

Synthesis and cytotoxic evaluation of novel quinazolinone derivatives as potential anticancer agents.

Nitrogen-rich heterocyclic compounds represent a unique class of chemicals with especial properties and have been modified to design novel pharmaceutically active compounds. In this study, a series of novel quinazolinone derivatives with substituted quinoxalindione were synthesized in two parts. In the first part, 6-(4-amino-3-methylphenoxy)quinoxaline-2,3(1H,4H)-dione was prepared from para-amino -m-crozol in 5 steps. In the next part, 2-alkyl-4H-benzo[d][1,3]oxazin-4-one derivatives were obtained from antranilic acid. Then reaction of 6-(4-amino-3-methylphenoxy)quinoxaline-2,3(1H,4H)-dione with 2-alkyl-4H-benzo[d][1,3]oxazin-4-one derivatives resulted in the production of final componds. The structures of synthesized compounds were confirmed by IR and 1H-NMR. Cytotoxic activity of the compounds were evaluated at 0.1, 1, 10, 50 and 100 µM concentrations against MCF-7 and HeLa cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Almost all new compounds showed cytotoxic activity in both cell lines. Among tested compounds, 11g displayed the highest cytotoxic activity against both cell lines.

Synthesis and evaluation of anticonvulsant activity of (Z)-4-(2-oxoindolin-3-ylideneamino)-N-phenylbenzamide derivatives in mice.

Due to resistance of some epileptic patients to the current medications and the general incidence of severe side effects of these drugs, development and discovery of novel antiepileptic drugs is crucial. Isatin-based derivatives are promising compounds as antiepileptic agents. In this study a new series of isatin-containing derivatives were synthesized via the imine formation between isatin and p-aminobenzoic acid. Subsequently, the obtained acidic compound was utilized to prepare the final amidic derivatives (4a-4l) through the reaction with various aniline derivatives. Then, their anti-seizure activity was investigated using maximal electroshock seizure (MES) as well as pentylenetetrazole (PTZ) models in mice. Neurotoxicity of target compounds was also determined by rotarod test. Tested isatin-based derivatives exhibited a favorable protection in both MES and PTZ procedures with high safety levels in neurotoxicity test. The introduced derivatives have demonstrated remarkable activity in mice and could be suggested as potential anticonvulsant lead compounds. All methoxylated derivatives (4j, 4k, 4l) showed a significant anti-seizure activity in MES model. Compounds 4j (2-OCH3) and 4l (4-OCH3) also demonstrated a potent anti-seizure activity against PTZ. Compound 4k (m-OCH3) did not induce protection towards PTZ-induced convulsion.

Synthesis and cytotoxic evaluation of some new 3-(2-(2-phenylthiazol-4-yl) ethyl)-quinazolin-4(3H) one derivatives with potential anticancer effects.

Quinazolinones are a group of heterocyclic compounds that have important biological activities such as cytotoxicity, anti-bacterial, and anti-fungal effects. Thiazole-containing compounds have also many biological effects including antitumor, antibacterial, anti-inflammatory, and analgesic activities. Due to significant cytotoxic effects of both quinazoline and thiazole derivatives, in this work a group of quinazolinone-thiazol hybrids were prepared and their cytotoxic effects on three cell lines were evaluated using MTT assay. Compounds A3, A2, B4, and A1 showed highest cytotoxic activities against PC3 cell line. Compounds A3, A5, and A2 were most active against MCF-7 and A3, A5, and A6 showed good cytotoxic effect on HT-29 cell line. According to the results, A3 efficiently inhibited all cell growth tested in a dose dependent manner. The IC50 of A3 was 10 M, 10 µM, and 12 µM on PC3, MCF-7, and HT-29 cells, respectively.

Synthesis and cytotoxicity evaluation of some new 6-nitro derivatives of thiazole-containing 4-(3H)-quinazolinone.

Quinazolinones are a group of fused heterocyclic compounds which have valuable biological properties including cytotoxic, antibacterial and antifungal activities. Thiazole group-containing compounds have been also reported to have a wide range of biological activities such as antitumor, anti-inflammatory, analgesic and antibacterial effects. Due to valuable cytotoxic effects of both thiazole groups and quinazoline derivatives, in this study a series of quinazolinone-thiazole hybrids were synthesized and evaluated for their cytotoxic effects on three cell lines including MCF-7, HT-29, and PC-3. Among tested compounds (quinazolinones and three intermediates), k5 and k6 showed highest cytotoxic activities against PC3 cell line. K6 and C were most active compounds against MCF7 and K6 showed best cytotoxicity on HT-29 cell line.

Quinazolinone and quinazoline derivatives: recent structures with potent antimicrobial and cytotoxic activities.

The heterocyclic compounds have a great importance in medicinal chemistry. One of the most important heterocycles in medicinal chemistry are quinazolines possessing wide spectrum of biological properties like antibacterial, antifungal, anticonvulsant, anti-inflammatory, anti-HIV, anticancer and analgesic activities. This skeleton is an important pharmacophore considered as a privileged structure. This review highlights the recent advances in the synthesis of quinazolines and quinazolinone derivatives with potent antimicrobial and cytotoxic activities.