Novel pyridine bearing pentose moiety-based anticancer agents: design, synthesis, radioiodination and bioassessments.

Pyridine compounds are one of the most important heterocyclic derivatives showing wide ranges in biological and pharmacological activities. Green chemistry eliminates or reduces the generation of hazardous compounds. It prevents pollution at a molecular level. The microwave technique used in heterocyclic compound synthesis is also an important branch of green chemistry techniques. In this study, we report designing and synthesizing a new pyridine-bearing pentose moiety via a one-pot multicomponent reaction using D-glucose and also investigate its behavior and reactivity toward some simple and heterocyclic amino derivatives. The chemical structures of the synthesized compounds were characterized and tested for their cytotoxic activities. Some of the test compounds exhibited slight to high cytotoxic activities against Caco2 (colon cancer) cells, HepG2 (hepatocellular carcinoma) cells and MCF-7 (human breast cancer) cells by MTT assay. The results showed clearly that compound 4 and compound 8 displayed strongest to moderate cytotoxic activity against the HepG2, Caco2 and MCF-7 respectively and compound 1 showed good activity against MCF-7 in comparison to the standard anticancer drug doxorubicin. These data were by cytopathological examination. An in-vivo radioactive tracing study of compound 4 proved its targeting ability to sarcoma cells in a tumor-bearing mice model. Our findings suggest that the synthesized compounds may be promising candidates as novel anticancer agents.

Green synthesis of highly functionalized heterocyclic bearing pyrazole moiety for cancer-targeted chemo/radioisotope therapy.

New derivatives of heterocyclic bearing pyrazole moiety were synthesized (eight new compounds from 2 to 9) via green synthesis methods (microwave-assisted and grinding techniques). 4,6-Diamino-1,3-diphenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (2) shows high anti-cancer activity against both HepG2 and HCT-116 with IC50 of 9.2 ± 2.8 and 7.7 ± 1.8 µM, respectively, which referenced to 5-Fu which is showing activity of 7.86 ± 0.5 and 5.35 ± 0.3 against both HepG2 and HCT-116, respectively. The cytotoxic activity against HCT-116 and HepG2 was slightly decreased and slightly increased, respectively, by a different pyrazole moiety (compound 5). Pharmacokinetics of compound 2 was carried out using the radioiodination technique in tumour-bearing Albino mice which shows good uptake at the tumour site. The biodistribution showed high accumulation in tumour tissues with a ratio of 13.7% ID/g organ after one hour in comparison with 2.97% ID/g organ at normal muscle at the same time point. As I-131 has maximum beta and gamma energies of 606.3 and 364.5 keV, respectively, therefore the newly synthesized compound 2 may be used for chemotherapy and TRT.

Conventional and microwave-assisted synthesis, anticancer evaluation, 99mTc-coupling and In-vivo study of some novel pyrazolone derivatives.

New pyrazolone derivatives were successfully synthesized by both microwave-assisted and conventional techniques. Compound 3 (3-(3-Methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)-3-oxopropanehydrazide) displayed remarkable anti-cancer activity (IC50 obtained at 8.71 and 10.63 µM for HCT-116 and MCF-7, respectively. Moreover, biodistribution study using radiolabeling approach revealed a remarked uptake of [99mTc]Tc-compound 3 complex into tumour induced in mice. The biodistribution showed high accumulation in tumour tissues with T/NT of 6.92 after 60 min post injection. As a result of these promising data, the newly synthesized compounds especially compound 3 affords a potential radio-carrier that could be used as a tumour marker and can be used for cancer therapy after further preclinical studies.