Synthesis and Cytotoxicity Activity of Some Novel Hydrazide, Pyrazole, Isoxazole, Pyrimidine and Fused Pyran-2-one Derivatives

Abstract

The reaction of 2-cyano-3-(dimethylamino)-N-((2-methoxynaphthalen-1-yl)methylene)acrylohydrazide (2) with some nitrogen nucleophiles, phenols and compounds, having an active methylene group to obtain polyfunctionally substituted azoles (3-5), azine (6), fused azines (7-10) and fused pyran-2-one derivatives (11-17).All the synthesized products were confirmed by elemental analysis, IR, 1 H-NMR, 13 C-NMR and MS data.The antitumor evaluation of the newly synthesized products against four human tumor cells lines namely hepatocellular carcinoma (liver) HepG-2, colorectal carcinoma (colon) HCT-116, mammary gland (breast) MCF-7 and epidermoid carcinoma (larynx) Hep-2 was investigated.Compound 4 exhibited superior in vitro antitumor activity in the 3-cell lines assay.Enaminonitriles are important intermediates for the synthesis of heterocyclic compounds having various biological activities. 1-7It's investigated and exhibited a wide range of bioactivities including antitumor, 8 antimicrobial, 9 antiviral, 10 analgesic, and anti-inflammatory drugs 11 have been reported.On the other hand, hydrazones possessing an azomethine group (-CONH-N=CH-) constituted an important class of compounds for new drug development 12 and showed a lot of bioactivity such as antimicrobial, 13 antitubercular, 14,15 anticonvulsant, 16 analgesic, 17 anti-inflammatory, 18,19 antiplatelet aggregation, 20 anticancer, 21,22 antifungal, 23 antiviral, 24 antibacterial 25 and antimalarial 26 activities.These facts have prompted us for the development of new hydrazones and evaluated for their antitumor activities.In continuation of our interest an ongoing program aiming at finding new structural leads with potential 1212