Biochemical profiling of anti-HIV prodrug Elsulfavirine (Elpida®) and its active form VM1500A against a panel of twelve human carbonic anhydrase isoforms

Claudiu T Supuran; Alessio Nocentini; Elena Yakubova; Nikolay Savchuk; Stanislav Kalinin; Mikhail Krasavin

doi:10.1080/14756366.2021.1927007

Biochemical profiling of anti-HIV prodrug Elsulfavirine (Elpida^®) and its active form VM1500A against a panel of twelve human carbonic anhydrase isoforms

J Enzyme Inhib Med Chem. 2021 Dec;36(1):1056-1060. doi: 10.1080/14756366.2021.1927007.

Authors

Claudiu T Supuran¹, Alessio Nocentini¹, Elena Yakubova², Nikolay Savchuk^{2

3}, Stanislav Kalinin⁴, Mikhail Krasavin⁴

Affiliations

¹ Neurofarba Department, Section of Pharmaceutical Sciences, University of Florence, Florence, Italy.
² Viriom Inc, San Diego, CA, USA.
³ ChemDiv Inc, San Diego, CA, USA.
⁴ Institute of Chemistry, St. Petersburg State University, St. Petersburg, Russia.

Abstract

The non-nucleoside reverse transcriptase inhibitor VM1500A is approved for the treatment of HIV/AIDS in its N-acyl sulphonamide prodrug form elsulfavirine (Elpida^®). Biochemical profiling against twelve human carbonic anhydrase (CA, EC 4.2.1.1) isoforms showed that while elsulfavirine was a weak inhibitor of all isoforms, VM1500A potently and selectively inhibited human (h) hCA VII isoform, a proven target for the therapy of neuropathic pain. The latter is a common neurologic complication of HIV infection and we hypothesise that by using Elpida^® in patients may help alleviate this debilitating symptom.

Keywords: N-acyl sulphonamide prodrug; Non-nucleoside reverse transcriptase inhibitor; elsulfavirine; human carbonic anhydrase; isoform selectivity; neuropathic pain.

MeSH terms

Amides / chemistry
Amides / pharmacology*
Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacology*
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Dose-Response Relationship, Drug
HIV / drug effects*
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Microbial Sensitivity Tests
Molecular Structure
Prodrugs / chemistry
Prodrugs / pharmacology*
Structure-Activity Relationship
Sulfones / chemistry
Sulfones / pharmacology*

Substances

Amides
Anti-HIV Agents
Carbonic Anhydrase Inhibitors
Isoenzymes
Prodrugs
Sulfones
Carbonic Anhydrases
elsulfavirine

Grants and funding

This research was supported by the Russian Federation Government Megagrant 14.W03.031.0025 (to MK) and by the Italian Ministry for Research and University, projects FISR2019_04819 BacCAD and PRIN prot. 2017XYBP2R (to CTS).