title: N1-substituted benzamidines: synthesis, antiproteinase activity and inhibition of tumor cell growth.
abstract: We have synthesized N1-substituted benzamidines and poly-benzamidines with the aim to produce antitumor drugs retaining differential biological properties with respect to unsubstituted compounds. Antiproliferative activity on in vitro cultured human leukemic cells was exhibited by N1-substituted poly-benzamidines, while N1-substituted benzamidines were found to retain very low antitumor effects. Furthermore, our results suggest that N1-substituted benzamidines and some of poly-benzamidines exhibit low activity on trypsin and kallikrein. Taken together these data indicate that some N1-substituted poly-benzamidines could be of interest for experimental antitumor therapy, since are likely to retain low side effects due to alteration of proteinase activity.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara.
authors.forename: R
authors.initials: R
authors.lastname: Ferroni
authors.forename: D
authors.initials: D
authors.lastname: Simoni
authors.forename: G
authors.initials: G
authors.lastname: Binato
authors.forename: C
authors.initials: C
authors.lastname: Nastruzzi
authors.forename: S
authors.initials: S
authors.lastname: Manfredini
authors.forename: P
authors.initials: P
authors.lastname: Orlandini
authors.forename: G
authors.initials: G
authors.lastname: Feriotto
authors.forename: R
authors.initials: R
authors.lastname: Gambari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001550:Benzamidines / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001550:Benzamidines; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; C074442:1,3-bis(4-amidinophenoxy)-2-(4-amidinophenoxymethyl)ethylpropane; C057885:1,3-di-(4-amidinophenoxy)-2,2-bis-(4-amidinophenoxymethyl)propane; D007610:Kallikreins; C005555:propamidine