Nitroguanidines and guanidino-containing hetereocycles as potential nitric oxide synthase inhibitors

Abstract

A series of amines were synthesized with yields of 71 to 99% for coupling with S-methyl-N-nitroisothiourea (SMNNITU) to form library MK-I and MK-II compounds. The yields obtained for library MK-I and MK-II compounds ranged from 48 to 75% and 37 to 47% respectively. Library MK-I and MK-II compounds were screened for their inhibitory activities against the three isoforms of NOS at 100uM. MK-I-09 had a thiophene group which may be able to fit into the active site pocket thereby causing a strong inhibiton of 120% with respect to the positive control (100%), L-NG-nitro-arginine (L-NNA).Another library of guanidino-containing hetereocycles was screened for their inhibitory activities against the nNOS at 100uM. Compound X gave the highest inhibition of 44% among the guanidino-containing hetereocycles screened. This could be due to stronger interactions (e.g. hydrogen bonding) of the sulphur with the active site.