Alba Chimirri

Integrase (IN) represents a clinically validated target for the development of antivirals against human immunodeficiency virus (HIV). In recent years our research group has been engaged in the stucture-function study of this enzyme and in the development of some three-dimensional pharmacophore models which have led to the identification of a large series of potent HIV-1 integrase strand-transfer inhibitors (INSTIs) bearing an indole core. To gain a better understanding of the structure-activity relationships (SARs), herein we report the design and microwave-assisted synthesis of a novel series of 1-H-benzylindole derivatives.

The replication cycle of human immunodeficiency virus type 1 (HIV‐1) is a complex multistep process that depends on both viral and host cell factors. The nuclear protein lens epithelium‐derived growth factor (LEDGF/p75) is a multidomain protein, present in host cells, which plays an important role in the integration process. LEDGF/p75 not only binds HIV‐1 integrase (IN) at its IN binding domain (IBD) but also contains several motifs that function in DNA and chromatin binding. The demonstrated importance of the association between IN and LEDGF/p75 in HIV‐1 integration suggests the possibility that this protein–protein interaction (PPI) could be exploited as an antiviral target. We describe herein the progress to date in developing inhibitors of this promising target.