%0 Journal Article
%T Synthesis of Novel Pyridopyridazin-3(2H)-one Derivatives and Evaluation of Their Cytotoxic Activity against MCF-7 Cells
%A Periasamy Selvakumar
%A Sathiah Thennarasu
%A Asit Baran Mandal
%J ISRN Medicinal Chemistry
%D 2014
%R 10.1155/2014/410716
%X 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¨C2f indicates the significance of the amide proton in pyridopyridazin-3(2H)-one derivatives. 1. Introduction Among the nitrogen containing six-member heterocylic compounds, the piperidine structural motif is often found in naturally occurring bioactive compounds such as alkaloids [1]. Piperidin-3-one derivatives are used as precursors for the synthesis of antimalarial agents, febrifugine, and isofebrifugine [2]. Piperidin-4-ones mostly display varied and potent biological properties such as antiviral, antitumour, analgesic, local anaesthetic, antimicrobial, fungicidal, herbicidal, insecticidal, antihistaminic, anti-inflammatory, anticancer, CNS stimulant, and depressant properties[3¨C9]. Recent reports suggest that compounds containing the piperidin-4-one moiety elicit excellent biological activities when aromatic substitutions are present at 2 and/or 6 positions [10]. Another pharmacologically important heterocyclic structural motif is the pyridazin-3(2H)-one unit, which has been found to inhibit the activities of cGMP-phosphodiesterase (PDE3) and cAMP-phosphodiesterase (PDE4) enzymes [11]. Also, pyridazin-3(2H)-one possesses different pharmacological activities like analgesic, anti-inflammatory, antibacterial, herbicidal, antifungal, antituberculotic, anti-AIDs, antitumour, antihypertensive, anticonvulsant, and antiviral activities [12¨C16]. Besides these activities, the polyfunctional tetrahydro-2H-pyrano[3,2-c]pyridazin-3(6H)-one derivatives have been shown to act as potent anticancer agents [17]. Recently, a series of pyridazinone derivatives bearing benzenesulfonamide moiety have also been reported to act as anticancer agents [18]. Mannich-type condensation involving a ketone having two active methylene groups, an aromatic aldehyde, and ammonium acetate, resulting in the formation of 2,6-diarylpiperidin-4-one, was first reported by Noller and Baliah [19]. Formation of 2,6-diarylpiperidin-4-one derivatives from the condensation of aryl aldehyde, ammonia, and levulinic acid or its ethyl ester was also
%U http://www.hindawi.com/journals/isrn.medicinal.chemistry/2014/410716/