A THEORETICAL STUDY OF THE INHIBITION OF WILD-TYPE AND DRUG-RESISTANT HTV-1 REVERSE TRANSCRIPTASE BY SOME THIAZOLIDENEBENZENESULFONAMIDE DERIVATIVES

摘要

We present the results of a quantum chemical study of the relationship between the electronic-conformational structure of a group of thiazolidenebenzenesulfo namide derivatives (TBS) and their Immunodeficiency Type 1 Virus (HTV-1) Reverse Transcriptase (RT, the wild one and two mutated types) inhibitory capacity. Our results show that the variation of the inhibitory capacity of TBS against the three types of HTV-1 RTs is regulated by different mechanisms. Also, as expected in a highly specific interaction, molecular orbitals other than the frontier molecular orbitals seem to regulate the inhibition of RT by TBS. The increase of the inhibitory capacity with increasing size of some substituents is not attributable to their interaction with a hydrophobic site but to their effect on the distribution of the rotational velocities. Specific n-n stacking interactions are the main components of the TBS-RT coupling. For each type of RT, the results provide a list of sites in the common skeleton that can be modulated through substitution to improve the inhibitory capacity.