Skip to main content

Improvement of Polybiguanide-based Microbicides Using Computational Design Methodologies

Polyethylene hexamethylene biguanide (PEHMB), a polybiguanide compound under development as a topical microbicide effective against HIV-1, was used as a starting point for rational design strategies and novel computational methods focused on identifying similar compounds with greater safety and activity. To investigate the hypothesis that PEHMB may represent a specific 3-D conformation and a degree of chain flexibility that confers the ability to inhibit HIV-1 infection through interactions with HIV-1 co-receptors, patented molecular calculation software (Shape Signatures) was used to predict bioisosteres of PEHMB. These analyses suggested that substitution of a bithiazole group for the ethylene spacers of PEHMB would provide backbone rigidity, nitrogen atom spacing, and electrostatic potentials similar to PEHMB. The resulting molecule, poly(hexamethylene-c-2, 2'-diamino-5, 5'-bithiazole (PHDB), was found to have similar cytotoxicity yet greater activity than PEHMB. These studies strongly support our strategy of design and synthesis of second-generation compounds based on the PEHMB motif.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mary L Ferguson.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Ferguson, M.L., Miller, S., Labib, M.E. et al. Improvement of Polybiguanide-based Microbicides Using Computational Design Methodologies. Retrovirology 2, P30 (2005). https://doi.org/10.1186/1742-4690-2-S1-P30

Download citation

Keywords

  • Nitrogen Atom
  • Electrostatic Potential
  • Design Methodology
  • Calculation Software
  • Biguanide