Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes

Abstrakt

HIV protease (HIV PR) is a primary target for anti-HIV drug design. We have previously identified and characterized substituted metallacarboranes as a new class of HIV protease inhibitors.

In a structure guided drug design effort, we connected the two cobalt bis(dicarbollide) clusters with a linker to substituted ammonium group. We explored inhibition properties of these compounds with various substitutions, determined the HIV PR:inhibitor crystal structure, and computationally explored the conformational space of the linker.

Our results prove the capacity of linker-substituted dual-cage cobalt bis(dicarbollides) as lead compounds for design of more potent inhibitors of HIV PR.

Klíčová slova

• HIV protease inhibitors
• aspartic proteases
• viral resistance
• cobalt bis(dicarbollide)
• crystal structure