Synthesis of Novel Pyridopyridazin-3(2H)-one Derivatives and Evaluation of Their Cytotoxic Activity against MCF-7 Cells

Abstract

A series of pyridopyridazin-3(2H)-one derivatives was synthesized in two facile steps. Mannich-type three-component condensation afforded the 2,6-diaryl piperidin-4-one derivatives, which underwent intramolecular cyclization in the presence of hydrazine or phenylhydrazine to yield the corresponding pyridopyridazin-3(2H)-one derivatives. All the derivatives of pyridopyridazin-3(2H)-one, except 3e and 3f, showed moderate activity against human breast adenocarcinoma (MCF-7) cells. The higher degree of inhibition of MCF-7 cell proliferation shown by 2a–2f indicates the significance of the amide proton in pyridopyridazin-3(2H)-one derivatives.

An approach of quantum chemical methods for the development and substantiation of the structure of new piperidine compounds

“…In the studies, the bond lengths of C=O, C-H, C=C (sp2hybridization of the carbon atom) and C-N calculated by the indicated methods were compared. The obtained data were compared with experimental data [27][28][29]. The C=C bond (a double carbon bond located in the benzene ring; the experimental value of the bond length is 1.395 Å) was calculated quite accurately by all methods, with a deviation ranging from -0.005 to +0.005.…”

Biological Potential and Chemical Properties of Pyridine and Piperidine Fused Pyridazine Compounds: Pyridopyridazine a Versatile Nucleus

“…The aryl ring at position 3 appears unimportant and reduces the activity against MCF-7 cells. The inhibitory activity of compounds against MCF-7 human breast adenocarcinoma cells, the importance of functional groups for the higher levels of activity shown by 21d, 21e and 21f 48 . This elaborated potential anticancer agents against breast cancer ( Figure 9).…”

“Pyridopyridazine”: A Versatile Nucleus in Pharmaceutical Field

“…Compounds 21a-c showed potent anticancer activity against MCF-7 breast cancer cell line relative to Doxorubicin as the standard drug. The antitumor potency is belonged to the electron withdrawing substituents in the aromatic ring besides the hydrazine incorporated in those derivatives [27]. This will open new avenue to elaborate potential anticancer agents against breast cancer (Figure 11).…”