Synthesis of new acridines and hydrazones derived from cyclic β-diketone for cytotoxic and antiviral evaluation

• Published in: European journal of medicinal chemistry 2009-09, Vol.44 (9), p.3680-3686
• Main Authors: El-Sabbagh, Osama I., Rady, Hanaa M.
• Format: Article
• Language: English
• Subjects: Acridines; Acridines - chemical synthesis; Acridines - chemistry; Acridines - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral activity; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Cytotoxic; Hepatitis A - drug therapy; Hepatitis A virus - drug effects; Humans; Hydrazones; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Liver - virology; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Semicarbazides - chemical synthesis; Semicarbazides - chemistry; Semicarbazides - pharmacology; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.04.001

Cyclic β-diketone namely, dimedone was utilized to prepare different chemical entities whether cyclic such as acridines, thiadiazole and triazole or acyclic systems as hydrazide, hydrazones, thiosemicarbazide and semicarbazide. The structures of the novel compounds were determined using elemental ana-lyses and various spectroscopic methods. Most acyclic derivatives especially semicarbazide 19, hydrazide 9 and thiosemicarbazide 16 showed a higher in vitro cytotoxic activity against hepatoma cell line (HepG2) than the cyclized acridine derivatives. The antiviral activity of the new compounds against Hepatitis A Virus (HAV) using the plague infectivity reduction assay revealed that the acridine 4 and the hydrazone 12 were more active than the reference drug amantadine. From cyclic β-diketone(dimedone, 1), nonclassical acridines, hydrazones and semicarbazide were synthesized. The semicarbazide 19 showed the highest in vitro cytotoxic activity against hepatoma cell line (HepG2). The antiviral study revealed that the acridine 4 and the hydrazone 12 were more active against Hepatitis A Virus than the reference drug amantadine upon using the plague infectivity reduction assay. [Display omitted]