New pyrazoles incorporating pyrazolylpyrazole moiety: Synthesis, anti-HCV and antitumor activity

• Published in: European journal of medicinal chemistry 2010-03, Vol.45 (3), p.1042-1050
• Main Authors: Riyadh, Sayed M., Farghaly, Thoraya A., Abdallah, Magda A., Abdalla, Mohamed M., Abd El-Aziz, Mohamed R.
• Format: Article
• Language: English
• Subjects: Animals; Anti-HCV; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antitumor activity; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Chromatography, High Pressure Liquid; Colonic Neoplasms - drug therapy; Cricetinae; Drug Screening Assays, Antitumor; Enaminones; Female; General and cellular metabolism. Vitamins; General aspects; Hepacivirus - drug effects; Hydrazonoyl chlorides; Medical sciences; Mice; Mice, Inbred C57BL; Molecular Structure; Pharmacology. Drug treatments; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrazolylpyrazole derivatives; Subacute Sclerosing Panencephalitis (SSPE); Subacute Sclerosing Panencephalitis - drug therapy
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.11.050

Three series of novel pyrazole derivatives 2b– d, 4a– d and 6a– d were synthesized via two step procedure that utilizes hydrazonoyl chlorides 1a– d and enaminones 3a– d and 5a– d, respectively as starting materials. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. Moreover, some of the products 2– 6 were tested against HCV and Subacute Sclerosing Panencephalitis (SSPE). In addition, compounds 2– 6 were also tested for the inhibition of peroxynitrite-induced tyrosine nitration and antioxidant activity. The tested compounds are highly effective at very low concentration as anti-HCV, SSPE antioxidant and anticancer in the following ascending order 2d, 4c, 6b, 3b, 6c, 4d, 2b, 2c, 2a, 6a, 5b, 5a, 3a, 4b and 5c. It is worth to mention that all tested compounds are more potent than the reference standards used for comparing activity. All the measurements revealed that the mechanism of action of the anti cancer activities of all the tested compounds is topoisomerase I inhibitor. [Display omitted]