Evaluation of the local anaesthetic activity of 3-aminobenzo[d]isothiazole derivatives using the rat sciatic nerve model.
On the basis of computer prediction of biological activity by PASS and toxicity by DEREK, the most promising 32-alkylaminoacyl derivatives of 3-aminobenzo[d]isothiazole were selected for possible local anaesthetic action. This action was evaluated using an in vitro preparation of the isolated sciatic nerve of the rat and compared with lidocaine which was used as a reference compound. QSAR studies showed that the polarizability, polarity and molecular shape of molecules have a positive influence on their local anaesthetic activity, while contributions of aromatic CH and singly bonded nitrogen are negative. Since the estimated PASS probabilities to find local anaesthetic activity in the most active compounds are less than 50%, these compounds may be considered to be possible NCEs.
School of Pharmacy, Department of Pharmaceutical Chemistry, Aristotle University, Thessaloniki 54124, Greece. geronik@pharm.auth.gr
Athina
A
Geronikaki
Paola
P
Vicini
Nikos
N
Dabarakis
Alexey
A
Lagunin
Vladimir
V
Poroikov
John
J
Dearden
Hassan
H
Modarresi
Mark
M
Hewitt
George
G
Theophilidis
D000779:Anesthetics, Local / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D003198:Computer Simulation; D008012:Lidocaine / Q000494:pharmacology; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects*
D000779:Anesthetics, Local; D052160:Benzothiazoles; D008012:Lidocaine