title: Benzisothiazole-1,1-dioxide alkanoic acid derivatives as inhibitors of rat lens aldose reductase.
abstract: Derivatives of 4-substituted 1,2-benzisothiazole-1,1-dioxide alkanoic acids were prepared and their in vitro aldose reductase inhibitory activity was tested in rat lens enzyme. The acetic derivatives 10, 12, and 16a-d proved to be much more potent inhibitors than the propionic derivatives 11, 13, and 17a-d. The presence of an acyl moiety on the amino group in position 4 of the acetic derivatives 16a-d led to a significant increase in activity with respect to the parent compound 14. One of the most active compounds in vitro, 10, was also evaluated in vivo as an inhibitor of glutathione lens depletion in galactosemic rats, but it did not show any activity in maintaining the rat lens glutathione level, probably due to problems of ocular bioavailability or metabolism.
authors.affiliation: Dipartimento di Scienze farmaceutiche dell'Università di Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Primofiore
authors.forename: F
authors.initials: F
authors.lastname: Da Settimo
authors.forename: C
authors.initials: C
authors.lastname: La Motta
authors.forename: F
authors.initials: F
authors.lastname: Simorini
authors.forename: A
authors.initials: A
authors.lastname: Minutolo
authors.forename: E
authors.initials: E
authors.lastname: Boldrini
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005693:Galactosemias / Q000201:enzymology / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D013844:Thiazoles; D000449:Aldehyde Reductase; D005978:Glutathione