Synthesis, X-ray crystal structure study, and cytostatic and antiviral evaluation of the novel cycloalkyl-N-aryl-hydroxamic acids.
In vitro evaluation of the novel cycloalkyl-N-(4-chlorophenyl)-hydroxamic acids (2a-g) demonstrated that 2b,d,e exhibited rather marked inhibitory activity (IC50 = 7-10 microM) against pancreatic carcinoma, 2b-d against colon carcinoma, 2d against laryngeal carcinoma, and 2b,d against breast carcinoma. 2e showed the most pronounced anti-cytomegalovirus activity (EC50 = 1.5 and 0.8 microg mL(-1)) only at > or = 5-fold lower than the cytotoxic concentration. 2d and 2f showed modest, albeit selective, activity against cytomegalovirus (2d, EC50 = 7.3-8.9 microg mL(-1), selectivity index 7-10; 2f, EC50 = 7-13 microg mL(-1), selectivity index 10).
Barbarić
Monika
M
Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia. mlovrek@yahoo.com
Ursić
Stanko
S
Pilepić
Viktor
V
Zorc
Branka
B
Hergold-Brundić
Antonija
A
Nagl
Ante
A
Grdisa
Mira
M
Pavelić
Kresimir
K
Snoeck
Robert
R
Andrei
Graciela
G
Balzarini
Jan
J
De Clercq
Erik
E
Mintas
Mladen
M
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003587:Cytomegalovirus / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000081:Acetamides; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D006877:Hydroxamic Acids; C497153:N-hydroxy-N-(4-chlorophenyl)adamantylformamide; C497152:N-hydroxy-N-(4-chlorophenyl)cyclohexylacetamide; D000218:Adamantane