No abstract

No abstract

O tratamento de 3-amino-2-metilquinazolina/6-bromo-2-metilquinazolina-4(3H)-onas, 2a,b, com 2,3-indolinediona na presença de traços de ácido acético glacial forneceu 3-{(2 -oxo-1 ,2 -dihidroindol-3 -ilideno)amino}-2-metilquinazolina/6-bromo-2-metilquinazolina-4-(3H)-onas, 3a,b, as quais foram condensadas com várias aminas secundárias e formaldeído em etanol para originar compostos do tipo 3-{(1 -alquil/arilaminometil-2 -oxo-1 ,2 -di-hidroindol-3 -ilideno)amino}-2-metil-6-quinazolin-4-(3H)-onas, 4a 1-6 e 4b 1-6 .Os compostos sintetizados foram caracterizados por análise elementar, espectroscopia no infravermelho, RMN 1 H e espectrometria de massas. Adicionalmente, foram investigadas suas atividades antimicrobiana, analgésica, anti-inflamatória e anti-helmíntica. Os resultados das atividades biológicas revelaram que os compostos 4a 3 , 4a 4 e 4b 6 exibiram atividades analgésica e anti-inflamatória significativas. Os compostos 4b 5 e 4b 6 apresentaram atividade anti-helmíntica, quando testados frente a Pheretima posthuma.The 3-amino-2-methylquinazoline/6-bromo-2-methylquinazoline-4(3H)-ones, 2a,b, on treatment with 2,3-indolinedione in the presence of traces of glacial acetic acid yielded 3-{(2 -oxo-1 ,2 -dihydroindole-3 -ylidene)amino}-2-methylquinazolin/6-bromo-2-methylquinazolin-4-(3H)-ones, 3a,b, which on condensation with various secondary amines and formaldehyde in ethanol afforded title compounds 3-{(1 -alkyl/arylaminomethyl-2 -oxo-1 ,2 -dihydroindole-3 -ylidene) amino}-2-methyl-6-quinazolin-4-(3H)-ones, 4a 1-6 and 4b 1-6 . C, H, N analysis, infrared spectroscopy, 1 H NMR, and mass spectroscopy allowed the identification of the synthesized compounds, which were investigated for their antimicrobial, analgesic, anti-inflammatory and antihelmintic activities. The results of the biological activities revealed that the compounds 4a 3 , 4a 4 and 4b 6 exhibited significant analgesic and anti-inflammatory activities. Compounds 4b 5 and 4b 6 showed antihelmintic activity when tested against Pheretima posthuma.

Objectives Cancer monotherapy is associated with various limitations; therefore, combination chemotherapy is widely explored for optimum drug efficacy. In this study, 4-(N-Phenyl-N′-substituted benzenesulfonyl)-6-(4-hydroxyphenyl) quinoline-based mammalian target of rapamycin (mTOR) inhibitor (IIIM-4Q) was investigated in combination with tocopherol succinate (TOS), and the mechanism of cytotoxicity was elucidated. Methods The cytotoxic potential of IIIM-4Q and TOS was evaluated in five cell lines. Further, to understand the mechanism of cytotoxicity of IIIM-4Q, TOS and their combination, various studies including morphological analysis using scanning electron microscopy and 6-diamidino-2-phenylindole (DAPI) staining, estimation of reactive oxygen species (ROS) level, measurement of mitochondrial membrane potential (MMP), in-vitro cell migration assay, Western blotting and staining with acridine orange (AO) for autophagy detection were performed. Key findings Investigated combination was synergistic in nature and exhibited greater oxidative stress and mitochondrial dysfunction in pancreatic cancer cells. The migration potential of MIA PaCa-2 cells was significantly mitigated under the influence of this combination, and morphological changes such as chromatin condensation and nuclear blebbing were observed. Also, poly (adenosine diphosphate-ribose) polymerase cleavage and caspase-3 activation were observed in IIIM-4Q and TOS combination-treated cells. Conclusions The investigated combination synergistically inhibited proliferation of MIA PaCa-2 cells through simultaneous induction of autophagy followed by apoptosis, and this combination demonstrated potential for further translational studies.