Mrinmoy Saha - Probing Mercaptobenzamides as HIV Inactivators via Nucleocapsid Protein 7

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      Publication Details (including relevant citation   information):

      ChemMedChem 2017

        DOI: 10.1002/cmdc.201700141

      Abstract:

        Human immunodeficiency virus type 1 (HIV-1) nucleocapsid   protein 7 (NCp7), a zinc finger protein, plays critical roles in   viral replication and maturation and is an attractive target for   drug development. However, the development of drug-like molecules   that inhibit NCp7 has been a significant challenge. In this   study, a series of novel 2-mercaptobenzamide prodrugs were   investigated for anti-HIV activity in the context of NCp7   inactivation. The molecules were synthesized from the   corresponding thiosalicylic acids, and they are all crystalline   solids and stable at room temperature. Derivatives with a range   of amide side chains and aromatic substituents were synthesized   and screened for anti-HIV activity. Wide ranges of antiviral   activity were observed, with IC50 values   ranging from 1 to 100 μm depending   on subtle changes to the substituents on the aromatic ring and   side chain. Results from these structure–activity relationships   were fit to a probable mode of intracellular activation and   interaction with NCp7 to explain variations in antiviral   activity. Our strategy to make a series of mercaptobenzamide   prodrugs represents a general new direction to make libraries   that can be screened for anti-HIV activity.

      Address (URL): http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201700141/full