Periphery Exploration around 2,6-Diazaspiro[3.4]octane Core Identifies a Potent Nitrofuran Antitubercular Lead-Reference-Cited by-同舟云学术

Periphery Exploration around 2,6-Diazaspiro[3.4]octane Core Identifies a Potent Nitrofuran Antitubercular Lead

Published:2023-03-10 Issue:6 Volume:28 Page:2529
ISSN:1420-3049
Container-title:Molecules
language:en
Short-container-title:Molecules

Author:

Lukin Alexei¹,Komarova Kristina¹,Vinogradova Lyubov¹,Dogonadze Marine²,Vinogradova Tatiana²,Yablonsky Piotr²,Kazantsev Alexander³,Krasavin Mikhail³⁴^ORCID

Affiliation:

1. Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 119454 Moscow, Russia

2. Saint Petersburg Research Institute of Phthisiopulmonology, 2-4 Ligovsky Prospekt, 191036 Saint Petersburg, Russia

3. Institute of Chemistry, Saint Petersburg State University, 26 Universitetskii Prospect, 198504 Peterhof, Russia

4. Institute of Living Systems, Immanuel Kant Baltic Federal University, 236041 Kaliningrad, Russia

Abstract

A small set of twelve compounds of a nitrofuran carboxamide chemotype was elaborated from a readily available 2,6-diazaspiro[3.4]octane building block, exploring diverse variants of the molecular periphery, including various azole substituents. The in vitro inhibitory activities of the synthesized compounds were assessed against Mycobacterium tuberculosis H37Rv. As a result, a remarkably potent antitubercular lead displaying a minimal inhibitory concentration of 0.016 μg/mL was identified.

Funder

Russian Foundation for Basic Research

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

Link

https://www.mdpi.com/1420-3049/28/6/2529/pdf

Reference13 articles.

1. Current development of 5-nitrofuran-2-yl derivatives as antitubercular agents;Elsaman;Bioorg. Chem.,2019

2. Trypanocidal activity of melamine-based nitroheterocycles;Stewart;Antimicrob. Agents Chemother.,2004

3. Conjugation of a 5-nitrofuran-2-oyl moiety to aminoalkylimidazoles produces non-toxic nitrofurans that are efficacious in vitro and in vivo against multidrug-resistant Mycobacterium tuberculosis;Krasavin;Eur. J. Med. Chem.,2018

4. Attachment of a 5-nitrofuroyl moiety to spirocyclic piperidines produces non-toxic nitrofurans that are efficacious in vitro against multidrug-resistant Mycobacterium tuberculosis;Krasavin;Eur. J. Med. Chem.,2019

5. Design, synthesis and evaluation of heteroaryldihydropyrimidine analogues bearing spiro ring as hepatitis B virus capsid protein inhibitors;Ma;Eur. J. Med. Chem.,2021