title: Cyanoacetic acid hydrazones of 3-(and 4-)acetylpyridine and some derived ring systems as potential antitumor and anti-HCV agents.
abstract: Two new acetylpyridinehydrazones derived from cyanoacetic acid hydrazide have been synthesized namely: cyanoacetic acid (1-pyridin-3 or 4-yl-ethylidene) hydrazides (1a,b). and some derived ring systems: 2-imino or 2-oxo-2H-chromenes (2a,b and 3a,b), substituted 2-thioxo-2,3-dihydrothiazoles (4a-d), substituted 2-thioxo-2,3-dihydro-6H-thiazolo[4,5-d]pyrimidin-7-ones (5a-d), substituted dihydrothiazoles (7a,b), and substituted 2-oxo-1,2-dihydropyridines (8a-d and 9a,b). Fifteen compounds were evaluated for their anticancer activity using the USA-NCI in-vitro screening program. Among the tested compounds, 8d exhibited a high value of percent tumor growth inhibition at concentrations of 10(-5) to 10(-7) M in all cancer cell lines, while 8b exhibited a significant value of percent tumor growth inhibition at concentration <10(-8 )M against non-small cells lung HOP-92. In addition, nine compounds were investigated for their in-vitro effect on the replication of hepatitis-C virus (HCV) in HepG2 hepatocellular carcinoma cell line infected with the virus using the reverse transcription polymerase chain reaction technique. Six compounds were capable of inhibiting the replication of both the HCV RNA (+)- and (-)-strands at 5-100 microg/mL concentration range. The activity order was 7b > 1b = 3a > 4c > 7a > 5c.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Egypt. SoadHawash@yahoo.com
authors.forename: Soad A M
authors.initials: SA
authors.lastname: El-Hawash
authors.forename: Abeer E
authors.initials: AE
authors.lastname: Abdel Wahab
authors.forename: Maha A
authors.initials: MA
authors.lastname: El-Demellawy
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D006834:Hydrazines; D011083:Polycyclic Compounds; D011725:Pyridines; C010835:3-acetylpyridine; C004703:cyacetacide; C055538:4-acetylpyridine