Naslov
Synthesis, X-Ray Crystal Structure Study, Cytostatic and Antiviral Evaluation of the Novel Cycloalkyl-N-aryl-hydroxamic Acids

Autori
Barbarić, Monika ; Uršić, Stanko ; Pilepić, Viktor ; Zorc, Branka ; Hergold-Brundić, Antonija ; Nagl, Ante ; Grdiša, Mira ; Pavelić, Krešimir ; Snoeck, Robert ; Andrei, Graciela ; Balzarini, Jan ; De Clercq, Erik ; Mintas, Mladen

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Drugs of the Future / Prous, J.R. - Kopenhagen, 2004, 438-438

Skup
XVIIIth International Symposium on Medicinal Chemistry

Mjesto i datum
Malmö, Švedska; Kopenhagen, Danska, 15.08.2004. - 19.08.2004

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Cycloalkyl-N-aryl-hydroxamic acids ; Cytostatic and Antiviral Evaluation ; 1H and 13C NMR study

Sažetak
The novel cycloalkyl-N-(4-chlorophenyl)-hydroxamic acids (2a-f) were synthesized by a specific approach which enabled a direct introduction of chloro substituent in the benzene ring, using acyl chloride and nitrosobenzene as starting reagents. The nonhalogenated compound 2g was prepared from the corresponding acyl chloride and N-phenylhydroxylamine. The structures of the compounds were deduced from their 1H and 13C NMR spectra. An unequivocal proof of the structure and conformation of 2d was established by X-ray crystallographic analysis. Compounds 2b, d, e and g exhibited rather marked inhibitory activity (IC50 = 7-80 mM) against malignant tumor cell lines: colon carcinoma (SW620), laryngeal carcinoma (Hep2), pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7) and cervical carcinoma (HeLa), but also against human normal fibroblasts (WI38). The best selectivity against tumor cell lines vs. normal fibroblasts was shown by compounds 2a and 2c. Compound 2e showed the most pronounced anti-CMV activity (EC50 = 1.5 and 0.8 mg mL-1) only at ≥ 5-fold lower than the cytotoxic concentration. Compounds 2d and 2f showed modest, albeit selective activity against cytomegalovirus (2d: EC50 = 7.3-8.9 mg mL-1, selectivity index 7-10, and 2f: EC50 = 7-13 mg mL-1 and selectivity index 10). These compounds represent therefore anti-CMV leads for further synthetic optimization.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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