Synthesis and comparison of substituted 1,2,3-dithiazole and 1,2,3-thiaselenazole as inhibitors of the feline immunodeficiency virus (FIV) nucleocapsid protein as a model for HIV infection

Christopher R M Asquith; Theres Meili; Tuomo Laitinen; Ilia V Baranovsky; Lidia S Konstantinova; Antti Poso; Oleg A Rakitin; Regina Hofmann-Lehmann

doi:10.1016/j.bmcl.2019.05.016

Synthesis and comparison of substituted 1,2,3-dithiazole and 1,2,3-thiaselenazole as inhibitors of the feline immunodeficiency virus (FIV) nucleocapsid protein as a model for HIV infection

Bioorg Med Chem Lett. 2019 Jul 15;29(14):1765-1768. doi: 10.1016/j.bmcl.2019.05.016. Epub 2019 May 9.

Authors

Christopher R M Asquith¹, Theres Meili², Tuomo Laitinen³, Ilia V Baranovsky⁴, Lidia S Konstantinova⁵, Antti Poso⁴, Oleg A Rakitin⁵, Regina Hofmann-Lehmann²

Affiliations

¹ Department of Pharmacology, School of Medicine University of North Carolina at Chapel Hill, NC 27599, USA. Electronic address: chris.asquith@unc.edu.
² Clinical Laboratory and Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich 8057, Switzerland.
³ School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio 70211, Finland.
⁴ Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russian Federation.
⁵ Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russian Federation; Nanotechnology Education and Research Center, South Ural State University, Lenina Ave. 76, Chelyabinsk 454080, Russian Federation.

PMID: 31101470
DOI: 10.1016/j.bmcl.2019.05.016

Abstract

We report the first biological evaluation the 1,2,3-thiaselenazole class of compound and utilising a concise synthetic approach of sulfur extrusion, selenium insertion of the 1,2,3-dithiazoles. We created a small diverse library of compounds to contrast the two ring systems. This approach has highlighted new structure activity relationship insights and lead to the development of sub-micro molar anti-viral compounds with reduced toxicity. The 1,2,3-thiaselenazole represents a new class of potential compounds for the treatment of FIV and HIV.

Keywords: Feline immunodeficiency virus (FIV); Human immunodeficiency virus (HIV); Nucleocapsid protein; Selenium; Zinc ejection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / pharmacology
Antiviral Agents / therapeutic use*
Cats
HIV Infections / drug therapy*
Immunodeficiency Virus, Feline / pathogenicity*
Nucleocapsid Proteins / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Antiviral Agents
Nucleocapsid Proteins