The novel phosphoramidate derivatives of NSAID 3-hydroxypropylamides: synthesis, cytostatic and antiviral activity evaluations.
The target phosphoramidates 5a-e were prepared in one step from 3-hydroxypropyl derivatives 3a-e of nonsteroidal anti-inflammatory drugs (fenoprofen, ketoprofen, ibuprofen, indomethacin, diclofenac). The products 3a-e and 5a-e were evaluated for their cytostatic and antiviral activity against malignant tumour cell lines and normal human fibroblasts (WI 38). All phosphoramidate derivatives 5a-e possess significantly greater inhibitory activities than the corresponding 3-hydroxypropyl derivatives 3a-e, whereby compound 5a showed the most potent inhibitory activities against cervical, pancreatic and colon carcinoma cell lines (IC(50)=5-7 microM).
Wittine
K
K
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000 Zagreb, Croatia.
Benci
K
K
Rajić
Z
Z
Zorc
B
B
Kralj
M
M
Marjanović
M
M
Pavelić
K
K
De Clercq
E
E
Andrei
G
G
Snoeck
R
R
Balzarini
J
J
Mintas
M
M
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents; D002460:Cell Line; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000138:chemical synthesis; D005347:Fibroblasts; D006801:Humans; D020128:Inhibitory Concentration 50; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D054697:Cytostatic Agents; D010756:Phosphoric Acids; C011067:phosphoramidic acid